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Treatment for pulmonary exacerbations of cystic fibrosis (CF) can produce a range of positive and negative outcomes. Understanding which of these outcomes are achievable and desirable to people affected by disease is critical to agreeing to goals of therapy and determining endpoints for trials. The relative importance of outcomes resulting from treatment of these episodes are not reported. We aimed to (i) quantify the relative importance of outcomes resulting from treatment for pulmonary exacerbations and (ii) develop patient and proxy carer-reported weighted outcome measures for use in adults and children, respectively.A discrete choice experiment (DCE) survey was conducted. Participants were asked to make a series of hypothetical decisions about treatment for pulmonary exacerbations to assess how they make trade-offs between different attributes of health. Data were analysed using a conditional logistic regression model. The correlation coefficients from these data were rescaled to enable generation of a composite health outcome score between 0 and 100 (worst to best health state).362 individuals participated (167 people with CF and 195 carers); of these, 206 completed the survey (56.9%). Most participants were female and resided in Australia. Difficult/painful breathing had the greatest impact on the preferred health state amongst people with CF and carers alike. Avoidance of gastrointestinal problems also heavily influenced decision-making.These data should be considered when making treatment decisions and determining endpoints for trials. Further research is recommended to quantify the preferences of children and to determine whether these align with those of their carer(s).

The considerable increase in labiaplasty requires plastic surgeons to be acquainted with the surgical techniques, their respective complications, and satisfaction rates. The authors conducted a systematic review of the available evidence on labia minoraplasty, looking at surgical techniques, clinical outcomes, and patient satisfaction.A comprehensive search across PubMed, Web of Science, SCOPUS, and CochraneCENTRAL was performed through October of 2020. A random-effects model meta-analysis was performed to assess satisfaction and complication rates.Forty-six studies including 3804 patients fulfilled the inclusion criteria. The pooled satisfaction rate after labia minoraplasty was 99 percent (95 percent CI, 97 to 99 percent). Substantial heterogeneity was present across studies ( I2 = 63.09 percent; p0.001). The highest pooled incidence of dehiscence was reported for laser-assisted labiaplasty (5 percent; 95 percent CI, 2 to 8 percent) and wedge resection (3 percent; 95 percent CI, 1 to 5 perecent). The highest pooled incidence of hematoma formation (8 percent; 95 percent CI,1 to 23 percent) and postoperative bleeding (2 percent; 95 percent CI,1 to 15 percent) was reported for W-shape resection. The highest pooled incidence of transient pain or discomfort was reported for de-epithelialization (2 percent; 95 percent CI,1 to 23 percent) and W-shape resection (2 percent; 95 percent CI,1 to 15 percent). Three cases of flap necrosis were reported; two occurred using wedge resection labia minoraplasty and one was not specified. The most common causes for revision surgery ( n = 169) were dehiscence and aesthetic concerns.Labia minoraplasty is a safe procedure, but serious complications requiring surgical management have been reported. Surgical experience, knowledge of female genital anatomy, and thorough technique selection in accordance with the patient characteristics are mandatory.

AIM: The purpose of this study was to explore the perceived value of certification among those with a neuroscience or stroke nursing certification. METHODS: The Perceived Value of Certification Tool-12 (PVCT-12) consists of 12 value statements related to the benefits of certification, using a 4-point Likert scale ranging from strongly disagree to strongly agree. Descriptive statistics were used to determine the percentage of agreement among respondents with each of the PVCT-12 items. A generalized linear model approach was then used to estimate the associations between age, sex, race, experience, certification, highest degree earned, primary responsibility, and primary work setting with intrinsic and extrinsic values. An exploratory factor analysis was performed to identify factors on which related variables were found. RESULTS: The 632 certificants were predominantly female (90%) with a mean age of 54 years. Approximately 80% were White, followed by Asian (11%), Hispanic (4%), and Black (3%). Certification included certified neuroscience registered nurse (34%), stroke certified registered nurse (47%), or both (20%). Approximately 57% of the certificants work in critical care/medical-surgical units. Work setting included academic (46%) and community (42%). Responses indicated lower levels of agreement with the value statements regarding certification challenges, professional autonomy, being listened to, and monetary gain. Those in administration had statistically significant higher intrinsic and extrinsic value scores ( P = .005) as compared with those in nonadministrative roles. There was no significant difference on perceived intrinsic or extrinsic values for those who work in an academic environment versus those who work in a community environment ( P = .25). After factor analysis, the PVCT-12 was found to have 3 factors that accounted for 53.4% of the total variation in the data: recognition of specialization, personal achievement, and professional accomplishment. CONCLUSION: The PVCT-12 incorporated a Likert-type scale to provide levels of agreement for intrinsic and extrinsic values among stroke certified registered nurses and certified neuroscience registered nurses. To complement these findings, further research using open-ended questions is needed to improve our understanding of participant responses regarding complex values such as "autonomy" and the "extent of being listened to."

Background: Default mode network (DMN) dysfunction is well established in Alzheimer’s disease (AD) and documented in both preclinical stages and at-risk subjects, thus representing a potential disease target. Multi-sessions of repetitive transcranial magnetic stimulation (rTMS) seem capable of modulating DMN dynamics and memory in healthy individuals and AD patients; however, the potential of this approach in at-risk subjects has yet to be tested. Objective: This study will test the effect of rTMS on the DMN in healthy older individuals carrying the strongest genetic risk factor for AD, the Apolipoprotein E (APOE) ɛ4 allele. Methods: We will recruit 64 older participants without cognitive deficits, 32 APOE ɛ4 allele carriers and 32 non-carriers as a reference group. Participants will undergo four rTMS sessions of active (high frequency) or sham DMN stimulation. Multimodal imaging exam (including structural, resting-state, and task functional MRI, and diffusion tensor imaging), TMS with concurrent electroencephalography (TMS-EEG), and cognitive assessment will be performed at baseline and after the stimulation sessions. Results: We will assess changes in DMN connectivity with resting-state functional MRI and TMS-EEG, as well as changes in memory performance in APOE ɛ4 carriers. We will also investigate the mechanisms underlying DMN modulation through the assessment of correlations with measures of neuronal activity, excitability, and structural connectivity with multimodal imaging. Conclusion: The results of this study will inform on the physiological and cognitive outcomes of DMN stimulation in subjects at risk for AD and on the possible mechanisms. These results may outline the design of future non-pharmacological preventive interventions for AD.

Objectives In Italy, free HPV vaccination has been offered to 12 years-old girls since 2007, while for males only since 2015. The aims of our study were: to measure HPV vaccination coverage among young women; to assess willingness to receive HPV vaccination among unvaccinated males and females; to evaluate the association of coverage and attitudes with knowledge regarding HPV and with sexual behavior. Methods A cross-sectional survey was conducted in an Italian region among 18–30 year-old students attending medical and healthcare professions schools. Participants completed a self-administered questionnaire exploring knowledge, attitudes and behaviors related to HPV infections, sexually transmitted diseases and their prevention. Information on vaccination status was also verified for each student through the immunization records provided by the participants during the occupational medical visit. Results 517 students were enrolled, with a 97% response rate. Of female participants, 40.5% had received at least one dose of HPV vaccine, while among unvaccinated participants, 60.5% stated their willingness to be vaccinated. A negative attitude towards HPV vaccination was associated with an older age, whereas a correct knowledge that both sexes are at risk of HPV infection, and the knowledge that vaccine protects against cervical cancer were confirmed to be associated to a willingness to receive HPV vaccination. Conclusions Our results showed low HPV vaccination coverage among young women and high reported willingness to receive vaccination among both sexes. More active education on the link between HPV and all related cancers could be beneficial to help prevent significant burden of the HPV-related diseases.

Headache is a common episodic and chronic pain syndrome in adolescents. Evaluation of headaches in primary care requires a comprehensive assessment including lifestyle behaviors and physical examination, as well as an understanding of when to pursue appropriate testing. Primary headache disorders seen in adolescents include migraine and tension-type headache. Pharmacologic management for primary headache includes both acute and prophylactic treatment strategies.

BACKGROUND: Oral propranolol accelerates the involution of infantile haemangiomas (IHs). However, it is not clear whether IHs treated with oral propranolol are associated with fewer sequelae than when left untreated. OBJECTIVES: To quantify and describe sequelae associated with IHs treated with oral propranolol, and to explore whether treated IHs are associated with fewer sequelae than untreated IHs. MATERIALS & METHODS: This multicentre, retrospective, cohort study included patients with IH treated with oral propranolol =2 mg/kg for at least six months, with photographic images available at baseline and at age 4-5 years. A historical comparison cohort comprised 185 patients with untreated IHs. Main outcomes/measures were: IH features, treatment characteristics and type/degree of sequelae. RESULTS: Oral propranolol, most commonly at 2 mg/kg/day (mean duration: nine months), was initiated in 171 patients (mean age: 6.02 months). After treatment, 125 of 171 (73.1%) IHs were associated with no/minimal sequelae. The most common sequelae were telangiectasia (78%), fibrofatty tissue (37%) and anetodermic skin (28%). Deep IHs were associated with significantly fewer sequelae than other subtypes. Ulceration appeared to increase the likelihood of severe sequelae. IHs with a stepped border was associated with more severe sequelae than those with a progressive border (44% versus 27%, p < 0.05). Treated IHs resolved without sequelae or were associated with a sequela that did not need correction in 27.7% more cases than untreated IHs (RR: 1.61; p < 0.001). CONCLUSION: Among IHs treated with oral propranolol, 73% resolved without, or were associated with minimal sequelae. Deep IHs were associated fewer sequelae than other subtypes. Oral propranolol decreased the likelihood of IH sequelae requiring correction.

International audience; This paper investigates the cognitive mechanisms supporting humans’ interpretation of requests for information. Learners can only search for a piece of information if they know that they are ignorant about it. Thus, in principle, the interpretation of requests for information could be guided by representations of Socratic ignorance (tracking what people know that they do not know). Alternatively, the interpretation of requests for information could be simplified by relying primarily on simple knowledge tracking (i.e., merely tracking what people know). We judged these hypotheses by testing two-and-a-half-year-old toddlers (N = 18), five- to seven-year-old children (N = 72), and adults (N = 384). In our experiments, a speaker asked a question that could be disambiguated by tracking her state of knowledge. We manipulated the speakers’ visuals to modulate the complexity of the ignorance representation required to disambiguate their questions. Toddlers showed no tendency to appeal to representations of Socratic ignorance when disambiguating questions (Pilot S1). Five- to seven-year-olds exhibited a similar pattern of results, and they performed better when information requests could be disambiguated using simple knowledge tracking (Studies 1a-1b). Adults used representations of Socratic ignorance to interpret questions, but were more confident when simple knowledge tracking was sufficient to disambiguate information requests (Studies 2-3). Moreover, adults disambiguated questions as if speakers could request information about things that they were ignorant of, even when speakers had no reason to know about their ignorance (Studies 3-4). Thus, the interpretation of requests for information rests primarily on simple knowledge tracking—and not on representations of Socratic ignorance—a heuristic that reduces processing costs.

Accurate and reproducible automated segmentation of human hippocampal subfields is of interest to study their roles in cognitive functions and disease processes. Multispectral structural MRI methods have been proposed to improve automated hippocampal subfield segmentation accuracy, but the reproducibility in a multicentric setting is, to date, not well characterized. Here, we assessed test–retest reproducibility of FreeSurfer 6.0 hippocampal subfield segmentations using multispectral MRI analysis pipelines (22 healthy subjects scanned twice, a week apart, at four 3T MRI sites). The harmonized MRI protocol included two 3D-T1, a 3D-FLAIR, and a high-resolution 2D-T2. After within-session T1 averaging, subfield volumes were segmented using three pipelines with different multispectral data: two longitudinal (“long_T1s” and “long_T1s_FLAIR”) and one cross-sectional (“long_T1s_FLAIR_crossT2”). Volume reproducibility was quantified in magnitude (reproducibility error—RE) and space (DICE coefficient). RE was lower in all hippocampal subfields, except for hippocampal fissure, using the longitudinal pipelines compared to long_T1s_FLAIR_crossT2 (average RE reduction of 0.4–3.6%). Similarly, the longitudinal pipelines showed a higher spatial reproducibility (1.1–7.8% of DICE improvement) in all hippocampal structures compared to long_T1s_FLAIR_crossT2. Moreover, long_T1s_FLAIR provided a small but significant RE improvement in comparison to long_T1s (p = 0.015), whereas no significant DICE differences were found. In addition, structures with volumes larger than 200 mm3 had better RE (1–2%) and DICE (0.7–0.95) than smaller structures. In summary, our study suggests that the most reproducible hippocampal subfield FreeSurfer segmentations are derived from a longitudinal pipeline using 3D-T1s and 3D-FLAIR. Adapting a longitudinal pipeline to include high-resolution 2D-T2 may lead to further improvements. Electronic supplementary material The online version of this article (10.1007/s00429-020-02172-w) contains supplementary material, which is available to authorized users.

BACKGROUND: This study aimed to examine intermediate-term outcomes of lung transplantation (LTx) recipients from donors after circulatory death (DCD).METHODS: We examined the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry data for patients transplanted between January 2003 and June 2017 at 22 centers in North America, Europe, and Australia participating in the DCD Registry. The distribution of continuous variables was summarized as median and interquartile range (IQR) values. Wilcoxon rank sum test was used to compare distribution of continuous variables and chi-square or Fisher's exact test for categorical variables. Kaplan-Meier survival rates after LTx from January 2003 to June 2016 were compared between DCD-III (Maastricht category III withdrawal of life-sustaining therapy [WLST]) only and donors after brain death (DBD) using the log-rank test. Risk factors for 5-year mortality were investigated using Cox multivariate proportional-hazards model.RESULTS: The study cohort included 11,516 lung transplants, of which 1,090 (9.5%) were DCD lung transplants with complete data. DCD-III comprised 94.1% of the DCD cohort. Among the participating centers, the proportion of DCD-LTx performed each year increased from 0.6% in 2003 to 13.5% in 2016. DCD donor management included extubation in 91%, intravenous heparin in 53% and pre-transplant normothermic ex vivo donor lung perfusion in 15%. The median time interval from WLST to cardiac arrest was 15 minutes (IQR: 11-22 minutes) and to cold flush 32 minutes (IQR: 26-41minutes). Compared with DBD, donor age was higher in DCD-III donors (46 years [IQR: 34-55] vs 40 years [IQR: 24-52]), bilateral LTx was performed more often (88.3% vs 76.6%), and more recipients had chronic obstructive pulmonary disease and emphysema as their transplant indication. Five-year survival rates were comparable (63% vs 61%, p = 0.72). In multivariable analysis, recipient and donor ages, indication diagnosis, procedure type (single vs bilateral and double LTx), and transplant era (2003-2009 vs 2010-2016) were independently associated with survival (p CONCLUSION: This ISHLT DCD Registry report with 5-year follow-up demonstrated similar favorable long-term survival in DCD-III and DBD lung donor recipients at 22 experienced centers globally. These data indicate that more extensive use of DCD-LTx would increase donor organ availability and may reduce waiting list mortality. (C) 2019 International Society for Heart and Lung Transplantation. All rights reserved.

Purpose The study examined the associations of multiple psychiatric and chronic conditions with the self-reported history of major depressive disorder (MDD) among patients with opioid use disorder (OUD) and tested whether the associations differed by gender. Methods We conducted a secondary data analysis of baseline data from a clinical trial including 1,646 participants with OUD, of which 465 had MDD. A variable cluster analysis was used to classify chronic medical and psychiatric conditions. Multivariable logistic regression analyses were used to estimate their associations with MDD in subjects with OUD. Results Nine variables were divided into three clusters: cluster 1 included heart condition, hypertension, and liver problems; cluster 2 included gastrointestinal (GI) problems and head injury, and cluster 3 included anxiety disorder, bipolar disorder, and schizophrenia. The overall prevalence of MDD in participants with OUD was 28.3% (22.8% for males and 39.5% for females). Gender, anxiety disorder, schizophrenia, liver problems, heart condition, GI problems, and head injury were significantly associated with MDD. Gender-stratified analyses showed that bipolar disorder, liver problems and individuals with one chronic condition were associated with MDD only in males, whereas heart condition, hypertension, and GI problems were associated with MDD only in females. In addition, anxiety disorder, head injury, individuals with one or more than two psychiatric conditions, and individuals with more than two chronic conditions were associated with MDD regardless of gender. Conclusions Treatment plans in patients with OUD should not only address MDD but also co-morbid psychiatric and chronic medical conditions that occur with MDD.

Burnout is endemic among oncology clinicians and impacts quality of care. In order to develop institutional strategies to address burnout, psychometrically sensitive measurement within local cancer organizations is necessary to identify embedded causes of burnout and resulting effects. The authors administered the Mini-Z burnout survey to clinicians and staff (n = 160) at a National Cancer Institute-designated comprehensive cancer center. Structural equation modeling was used to examine workplace stressors that predicted burnout, and the pathway between burnout and 2 meaningful quality outcomes was tested: (1) lack of compassion and (2) thoughts of leaving one's job or specialty. Females and advanced practice practitioners had the highest prevalence of burnout. The structural equation model achieved excellent model fit, and indicated that workplace atmosphere, control over workload, values alignment, time for documentation, and team efficiency underlie burnout in this sample. The pathways from burnout to lack of compassion and to thoughts of leaving one's job were significant.

International audience; Source representations play a role both in the formation of individual beliefs as well as in the social transmission of such beliefs. Both of these functions suggest that source information should be particularly useful in the context of interpersonal disagreement. Three experiments with an identical design (one original study and two replications) with 3-to 4-year-oldchildren (N = 100) assessed whether children's source memory performance would improve in the face of disagreement and whether such an effect interacts with different types of sources (first-vs. secondhand). In a 2 x 2 repeated-measures design, children found out about the contents of a container either by looking inside or being told (IV1). Then they were questioned about the contents of the container by an interlocutor puppet who either agreed or disagreed with their answer (IV2). We measured children's source memory performance in response to a free recall question (DV1) followed by a forced-choice question (DV2). Four-year-olds (but not three-year-olds) performed better in response to the free recall source memory question (but not the forced-choice question) when their interlocutor had disagreed with them compared to when it had agreed with them. Children were also better at recalling 'having been told' than 'having seen'. These results demonstrate that by four years of age, source memory capacities are sensitive to the communicative context of assertions and serve social functions.

Summary Background Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders. Methods Our study was done in three stages. First, we did genome-wide linkage analysis of an Italian family with dominantly inherited Parkinson's disease to identify the disease locus. Second, we sequenced the candidate gene in an international multicentre series of unrelated probands who were diagnosed either clinically or pathologically with Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. As a control, we used gene sequencing data from individuals with abdominal aortic aneurysms (who were not examined neurologically). Third, we enrolled an independent series of patients diagnosed clinically with Parkinson's disease and controls with no signs or family history of Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies from centres in Portugal, Sardinia, and Taiwan, and screened them for specific variants. We also did mRNA and brain pathology studies in three patients from the international multicentre series carrying disease-associated variants, and we did functional protein studies in in-vitro models, including neurons from induced pluripotent stem-like cells. Findings Molecular studies were done between Jan 1, 2008, and Dec 31, 2017. In the initial kindred of ten affected Italian individuals (mean age of disease onset 59·8 years [SD 8·7]), we detected significant linkage of Parkinson's disease to chromosome 14 and nominated LRP10 as the disease-causing gene. Among the international series of 660 probands, we identified eight individuals (four with Parkinson's disease, two with Parkinson's disease dementia, and two with dementia with Lewy bodies) who carried different, rare, potentially pathogenic LRP10 variants; one carrier was found among 645 controls with abdominal aortic aneurysms. In the independent series, two of these eight variants were detected in three additional Parkinson's disease probands (two from Sardinia and one from Taiwan) but in none of the controls. Of the 11 probands from the international and independent cohorts with LRP10 variants, ten had a positive family history of disease and DNA was available from ten affected relatives (in seven of these families). The LRP10 variants were present in nine of these ten relatives, providing independent—albeit limited—evidence of co-segregation with disease. Post-mortem studies in three patients carrying distinct LRP10 variants showed severe Lewy body pathology. Of nine variants identified in total (one in the initial family and eight in stage 2), three severely affected LRP10 expression and mRNA stability (1424+5delG, 1424+5G→A, and Ala212Serfs*17, shown by cDNA analysis), four affected protein stability (Tyr307Asn, Gly603Arg, Arg235Cys, and Pro699Ser, shown by cycloheximide-chase experiments), and two affected protein localisation (Asn517del and Arg533Leu; shown by immunocytochemistry), pointing to loss of LRP10 function as a common pathogenic mechanism. Interpretation Our findings implicate LRP10 gene defects in the development of inherited forms of α-synucleinopathies. Future elucidation of the function of the LRP10 protein and pathways could offer novel insights into mechanisms, biomarkers, and therapeutic targets. Funding Stichting ParkinsonFonds, Dorpmans-Wigmans Stichting, Erasmus Medical Center, ZonMw—Memorabel programme, EU Joint Programme Neurodegenerative Disease Research (JPND), Parkinson's UK, Avtal om Lakarutbildning och Forskning (ALF) and Parkinsonfonden (Sweden), Lijf and Leven foundation, and cross-border grant of Alzheimer Netherlands–Ligue Europeene Contre la Maladie d'Alzheimer (LECMA).

Objectives The frozen elephant trunk (FET) technique allows one-stage hybrid repair approach in aortic dissection (AoD). Even if the effect of the FET technique on promoting false lumen (FL) thrombosis has been proved in the past, the relative importance of FL thrombosis on aortic remodelling at different levels of the distal aorta and the magnitude of this effect is not well known. The aim of the study was to evaluate aortic remodelling following a FET technique for AoD. Methods A multicentre international registry database was searched to identify all patients who underwent a FET procedure for an AoD. A total of 383 patients with AoD were operated on between January 2005 and March 2014 with the FET technique; 137 patients (65 acute AoD and 72 chronic AoD) who survived the initial repair with at least a 1-year follow-up CT scan were included in the study. Results The rate of FL thrombosis was higher in the mid-descending thoracic aorta (99.3%) and lower in the distal abdominal aorta (13.9%) but similar between acute and chronic AoDs. The negative remodelling rate was similar between acute and chronic AoDs in the abdominal aorta, but chronic AoD exhibited a higher rate of negative remodelling in the descending thoracic aorta (33% vs 17.5%, P = 0.040). Conclusions The FET technique provides an effective treatment for AoD, promoting FL thrombosis and remodelling in the descending thoracic aorta. Changes in the diameter of the aortic lumen depend mainly on the status of the FL and are similar between acute and chronic AoD. Changes in the diameter of true lumen are affected by both the FL status and the timing of the presentation. However, increased FL thrombosis and positive remodelling rates are not maintained at the level of the abdominal aorta, and strict follow-up is mandatory to detect early changes in the aortic dimensions, which may warrant further interventions.

BACKGROUND: Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium-glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS: In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin-angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of

Posttraumatic stress disorder (PTSD) and insomnia are characterized by sleep disturbances and daytime functional impairments. Actigraphy metrics can quantify diurnal rhythms via interdaily stability, intradaily variability, relative amplitude, and sleep regularity. Here, we (a) compared diurnal rhythms in PTSD, insomnia, and healthy control samples using linear mixed modeling; (b) compared inter-individual variability of diurnal rhythms between groups using variance ratio tests; and (c) examined correlations between diurnal rhythms and sleep measures within the clinical samples. Participants ( N = 98) wore wrist-activity monitors for one week and completed the Insomnia Severity Index and Pittsburgh Sleep Quality Index. Both clinical samples displayed significantly lower interdaily stability, relative amplitude, and sleep regularity compared with controls. Individuals with PTSD and insomnia did not differ on mean diurnal rhythm metrics. Both clinical samples showed more inter-individual variability in relative amplitude compared with controls, and the individuals with PTSD were distinguished from those with insomnia by greater inter-individual variability in interdaily stability and relative amplitude. Relative amplitude in the clinical samples was positively correlated with objective sleep efficiency and total sleep time. This is the first study to compare individuals with PTSD and insomnia on measures of diurnal rhythms, revealing those with PTSD and insomnia to have less robust and more variable diurnal rhythms compared with controls. Individuals with PTSD differed from those with insomnia in inter-individual variability of diurnal rest-activity stability and amplitude, highlighting this population as particularly heterogenous. Diurnal rhythm robustness might be considered an intervention target in insomnia and PTSD populations.

Anxiety is prevalent among hospital inpatients and it has harmful effects on patient well-being and clinical outcomes. We aimed to characterize the sources of hospital distress and their relationship to anxiety. We conducted a cross-sectional study of inpatients (n = 271) throughout two Southeastern U.S. metropolitan hospitals. Participants completed a survey to identify which of 38 stressors they were experiencing. They also completed the State Trait Anxiety Inventory six-item scale. We evaluated the prevalence of stressors, their distribution, and crude association with anxiety. We then used multivariate logistic regression to estimate the association between stressors and clinically relevant anxiety, with and without adjusting for demographic variables. We used factor analysis to describe the interrelationships among stressors and to examine whether groups of stressors tend to be endorsed together. The following stressors were highly endorsed across all unit types: pain, being unable to sleep, feelings of frustration, being overwhelmed, and fear of the unknown. Stressors relating to isolation/meaninglessness and fear/frustration tend to be endorsed together. Stressors were more frequently endorsed by younger, female, and uninsured or Medicaid-insured patients and being female and uninsured was associated with anxiety in bivariate analysis. After controlling for the sources of distress in multivariate linear analysis, gender and insurance status no longer predicted anxiety. Feelings of isolation, lack of meaning, frustration, fear, or a loss of control were predictive. Study results suggest that multiple stressors are prevalent among hospital inpatients and relatively consistent across hospital unit and disease type. Interventions for anxiety or emotional/spiritual burden may be best targeted to stressors that are frequently endorsed or associated with anxiety, especially among young and female patients.

STUDY OBJECTIVES: Sleep disturbance is common in those who experience trauma. In a sample of nontreatment-seeking refugees, we examined the associations between trauma exposure, postmigration stress, sleep symptoms, and posttraumatic psychological symptoms. METHODS: Syrian and Iraqi refugees (n = 86; 51% female; mean age = 45 years) residing in Australia were recruited from the local community. Cross-sectional descriptive design, multinominal regression analyses, and mediation analyses were used. Participants completed measures in Arabic assessing premigration trauma exposure, postmigration stress, sleep symptoms, and mental health. They also completed 7 days of sleep diaries and actigraphy. RESULTS: We identified 34.9% of the participants as normal sleepers, 32.6% as probably having insomnia, and 32.6% as likely having insomnia. Variables associated with greater sleep disturbance (McFadden’s R(2) = 0.57) included greater trauma exposure, increased time of resettlement, greater postmigration stress, and greater presleep arousal. The association of premigration trauma exposure to current posttraumatic symptoms was mediated sequentially by postmigration stress and sleep symptoms. CONCLUSIONS: Our findings highlight the extent of sleep disturbance in refugees. We found evidence for an indirect pathway between trauma exposure and posttraumatic symptoms through premigration stress and sleep (particularly presleep arousal). In the current global refugee crisis, improving the existing system of care in countries experiencing increased migration is critical. Because sleep disturbance is a modifiable condition associated with mental health, targeting sleep could be an important component of psychological interventions for refugees. CITATION: Lies J, Jobson L, Mascaro L, Whyman T, Drummond SPA. Postmigration stress and sleep disturbances mediate the relationship between trauma exposure and posttraumatic stress symptoms among Syrian and Iraqi refugees. J Clin Sleep Med. 2021;17(3):479–489.

Background: Preeclampsia is a multiorgan disorder associated with maternal and perinatal morbi-mortality. In Peru, incidence is 10% and accounts for 22% of maternal deaths. Genome and genetic epidemiological studies have found an association between preeclampsia and genetic polymorphisms. Objective: To determine the association of the vascular endothelial growth factor (VEGF) +936 C/T and +405 G/C, interleukine-6 (IL-6) -174 G/C, IL-1β-511 C/T, Apo A-1-75 G/A, Apo B-100 2488 C/T (Xbal) polymorphisms with preeclampsia in pregnant Peruvian women. Methods: Were included preeclamptic and healthy (control) pregnant women. Maternal blood samples were subjected to DNA extraction, and molecular genetic analysis was conducted using the PCR-RFLP technique and following a specific protocol for each gene. Allele and genotypic frequencies in the cases and controls were compared. Results: No association was found between the VEGF+936C/T and VEGF+405 polymorphisms and preeclampsia. The frequencies of the GG genotypes and the G allele of the -174 G/C polymorphism in the IL6 gene in preeclamptic and controls showed significant differences, with higher frequencies in cases. For the -511 C/T polymorphism of the IL-1β gene, no significant differences were found in the frequencies of TT genotypes compared with CT+CC. The genotypes and alleles of the Apo-A1-75 G/A and Apo-B100 Xbal variants showed no significant differences between cases and controls. Conclusion: No association was found between the studied genetic markers and preeclampsia. However, in the -174G/C polymorphism of the IL-6 gene, significant differences were found mainly in the GG genotype and G allele. Resumen Antecedentes: La preeclampsia es un trastorno multiorgánico asociado con la morbi-mortalidad materna y perinatal. En el Perú, su incidencia es del 10% y causa el 22% de las muertes maternas. Se encontró una asociación entre la preeclampsia y ciertos polimorfismos. Objetivo: Determinar asociación entre los polimorfismos genéticos del factor de crecimiento endotelial vascular (VEGF) +936 C/T y +405 G/C, interleucina-6 (IL-6) -174G/C, IL-1β -511 C/T, Apo A-1 -75 G/A, Apo B-100 2488 C/T (Xbal), y preeclampsia en gestantes peruanas. Métodos: Se incluyeron gestantes preeclámpticas y sanas (controles). Las muestras de sangre fueron procesadas para extracción del ADN, y el análisis se realizó con la técnica PCR-RFLP con protocolos específicos para cada gen y confirmación con secuenciamiento Sanger. Se compararon las frecuencias alélicas y genotípicas en los casos (preeclampsia) y los controles. Resultados: No se halló asociación entre los polimorfismos VEGF+936-C/T y VEGF+405 y la preeclampsia. Las frecuencias de los genotipos GG y el alelo G del polimorfismo -174-G/C en el gen IL6 en preeclámpticas y controles, mostraron diferencias significativas, con frecuencias más altas en los casos. Para el polimorfismo -511-C/T del gen IL-1β, no se encontraron diferencias significativas en las frecuencias de genotipos TT comparados con CT+CC. Los genotipos y alelos de las variantes Apo-A1-75-G/A y Apo-B100 Xbal no mostraron diferencias significativas entre los grupos Conclusión: No se encontró asociación entre los marcadores genéticos estudiados y la preeclampsia. Sin embargo, el polimorfismo -174-G/C en el gen IL6 mostró diferencias significativas principalmente en el genotipo GG y el alelo G.

Background Coronavirus Disease 2019 (COVID-19) pandemic had an overwhelming impact on healthcare worldwide. Outstandingly, the aftermath on neoplastic patients is still largely unknown, and only isolated cases of COVID-19 during radiotherapy have been published. We will report the two-months experience of our Department, set in Lombardy “red-zone”. Methods Data of 402 cancer patients undergoing active treatment from February 24 to April 24, 2020 were retrospectively reviewed; several indicators of the Department functioning were also analyzed. Results Dedicated measures allowed an overall limited reduction of the workload. Decrease of radiotherapy treatment number reached 17%, while the number of administration of systemic treatment and follow up evaluations kept constant. Conversely, new treatment planning faced substantial decline. Considering the patients, infection rate was 3.23% (13/402) and mortality 1.24% (5/402). Median age of COVID-19 patients was 69.7 years, the large majority were male and smokers (84.6%); lung cancer was the most common tumor type (61.5%), 84.6% of subjects were stage III-IV and 92.3% had comorbidities. Remarkably, 92.3% of the cases were detected before March 24. Globally, only 2.5% of ongoing treatments were suspended due to suspect or confirmed COVID-19 and 46.2% of positive patients carried on radiotherapy without interruption. Considering only the last month, infection rate among patients undergoing treatment precipitated to 0.43% (1/232) and no new contagions were reported within our staff. Conclusions Although mortality rate in COVID-19 cancer patients is elevated, our results support the feasibility and safety of continuing anticancer treatment during SARS-Cov-2 pandemic by endorsing consistent preventive measures.

Diseases of the thoracic aorta are increasing in prevalence worldwide. Recent data indicated wide regional variation in the volume and complexity of aortic cases undertaken in United Kingdom cardiac centers, especially in case of acute type A aortic dissection (ATAAD) conditions. Patients treated in high-volume centers with a specific multidisciplinary aortic program had a significant reduction in ATAAD mortality when compared with low-volume centers. Following the initial phase of a national aortic center reorganization, the current study reflects the initial experience of a national collective of cardiothoracic surgeons with expertise in complex aortic surgery, using frozen elephant trunk as standard technique for the surgical treatment of patients affected by ATAAD. Between June 2013 and October 2017, 66 ATAAD patients (45% women) underwent hybrid aortic arch and frozen elephant trunk repair with the Thoraflex hybrid graft at 8 UK high-volume aortic centers. The in-hospital mortality accounted for 8 patients (12%). Postoperative temporary or permanent neurologic events and temporary renal replacement therapy occurred in 17% and 20% of patients, respectively. No spinal cord injury events were documented. Our data were similar to those reported in literature in the 2 largest experiences with the use of frozen elephant technique in ATAAD condition (in-hospital/30-day mortality: 11-12%). This initial experience demonstrated that frozen elephant technique can potentially be adopted as standard approach in life-threatening aortic diseases, with acceptable complication and mortality rates.

Apoptosis not only eliminates cells that are damaged or dangerous but also cells whose function during development in patterning or organogenesis is complete. The successful formation of germ cells is essential for the perpetuation of a species. The production of an oocyte often depends on signaling between germline and somatic cells, but also between specialized types of somatic cells. In Drosophila, each developing egg chamber is separated from the next by a single file of interfollicular somatic cells. Little is known about the function of the interfollicular stalk, although its presumed role in separating egg chambers is to ensure that patterning cues from one egg chamber do not impact or disrupt the development of adjacent egg chambers. We found that cells comprising the stalk undergo a progressive decrease in number during oogenesis through an apoptotic-dependent loss. The extent of programmed cell death is restricted by JAK/STAT signaling in a cell-autonomous manner to ensure that the stalk is maintained. Both a failure to undergo the normal reduction in stalk cell number, or to prevent excessive stalk cell apoptosis results in a decrease in fecundity. Thus, activation of JAK/STAT signaling in the Drosophila interfollicular stalk emerges as a model to study the tight regulation of signaling-dependent apoptosis.

Background The aims of the study are to evaluate attitudes about childhood vaccines and vaccine refusal or delay among parents and to assess the role played by the variables mapped as potential determinants to suggest strategies that could improve childhood vaccination rates. Methods The cross-sectional study was intended for parents of kindergarteners. Parental attitudes were measured using the Parent Attitudes about Childhood Vaccines (PACV) survey, to screen for Vaccine Hesitancy (VH). In addition, selected factors have been grouped in three categories (contextual, individual and group and vaccine/vaccination-specific influences), and were explored as potential determinant of VH and vaccination refusal or delay. Results 7.7% of subjects were defined as VH parents (VHPs) through PACV score, while 24.6% reported having refused or delayed at least one dose of vaccine for their child. VH was more common in those parents that decided not to vaccinate their child after having received information from mass-media, in those who did not agree with mandatory vaccinations, and in those who agreed with political leaders who oppose to vaccination. Vaccine refusing/delaying parents were more frequently those who agreed that infant vaccinations are primarily an economic business of pharmaceutical companies, and who disagreed that access to the kindergarten should only be allowed to children who had been vaccinated. Conclusion The findings of the present study emphasize the importance of PACV as a tool to screen VHPs. Furthermore, results highlight important potential determinants of VH, such as communication and media environment, and attitudes about prevention. Health care providers could act as key components to improve the public trust to scientific and epidemiological evidence.

We measured the prevalence of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) in swine livestock workers, examined LA-MRSA resistance profile, and associated carriage with the working activities.Information was collected on demographics and occupational history. Swabs were collected and tested for the isolation of S. aureus, examined for antimicrobial susceptibility, and all MRSA underwent ST398qPCR assay.LA-MRSA was isolated in 7.3% of the 396 enrolled workers. LA-MRSA colonization was more likely in farmers than in slaughterhouse workers (Fisher exact P = 0.001). Carriage was associated with herd size, being less frequent in small/medium farms (odds ratio = 0.20; 95% confidence interval = 0.07 to 0.53), and with the number of working days per week (OR = 2.11; 95% confidence interval = 1.07 to 4.19).LA-MRSA carriage is strongly animal-exposure related, and educational intervention informing about the risks related to the activity with livestock is needed.

Objective: Photobiomodulation (PBM) can modulate the proliferation of some types of stem cells. However, few reports have addressed the effects of PBM delivered by light-emitting diode (LED) on stem cells obtained from the pulp tissue of deciduous teeth. The aim of the present study was to investigate the effect of PBM delivered by red LED (630 nm, 75 mW, 37 mW/cm2) with different radiant exposures on the cell cycle, mitochondrial membrane potential, and senescence of stem cells from human exfoliated deciduous teeth (SHED). Materials and methods: Cultures were irradiated with LED (2, 4, 8, 16, and 32 J/cm2). After 24 h, the cell cycle and mitochondrial membrane potential of the cultures were evaluated using flow cytometry. Nonirradiated cultures served as control. Results: Cultures irradiated with 16 J/cm2 had higher percentages of cells in the synthesis phase than control cultures (p

This article investigates the early emergence of reason-giving. Toddlers are sensitive to disagreements, and they can track several kinds of informational access, such as visual perception. We investigated whether young children use these skills (a) when assessing whether providing reasons is needed and (b) when selecting appropriate behaviors to support their claims. An experimenter disagreed with 2- to 4-year-old children (N = 71) about the location of a toy placed in 1 of 4 boxes. In the fully transparent condition, the boxes were transparent, and the toy was visible to the experimenter and to the participant. In the window condition, the boxes were partially opaque, and the toy was initially hidden from the experimenter but visible to the participant through a transparent window. In this condition, toddlers could make the toy visible to the experimenter by rotating the baited box. Participants in the window condition were more likely to rotate the baited box than those in the transparent condition. Thus, children were more likely to rotate the box when this action was an efficient way of supporting their claims by revealing new and relevant information to the experimenter. These results demonstrate the presence of precursors of crucial skills required for reason-giving and reveal that from 2 years of age, children do not use fixed persuasion strategies. Instead, they select relevant evidence when attempting to influence others. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Background Borderline Personality Disorder (BPD) is a complex and debilitating disorder, characterized by deficits in metacognition and emotion dysregulation. The “gold standard” treatment for this disorder is psychotherapy with pharmacotherapy as an adjunctive treatment to target state symptoms. The present randomized clinical trial aims to assess the clinical and neurobiological changes following Metacognitive Interpersonal Therapy (MIT) compared with Structured Clinical Management (SCM) derived from specific recommendations in APA (American Psychiatric Association) guidelines for BPD. Methods The study design is a randomized parallel controlled clinical trial and will include 80 BPD outpatients, aged 18–45 enrolled at 2 recruitment centers. Primary outcome will be the clinical change in emotion regulation capacities assessed with the Difficulties in Emotion Regulation Scale (DERS). We will also investigated the effect of psychotherapy on metacognitive abilities and several clinical features such as BPD symptomatology, general psychopathology, depression, personal functioning, and trait dimensions (anger, impulsivity, alexithymia). We will evaluate changes in brain connectivity patterns and during the view of emotional pictures. A multidimensional assessment will be performed at the baseline, at 6, 12, 18 months. We will obtain structural and functional Magnetic Resonance Images (MRIs) in MIT-Treated BPD (N = 30) and SCM-treated BPD (N = 30) at baseline and after treatment, as well as in a group of 30 healthy and unrelated volunteers that will be scanned once for comparison. Discussion The present study could contribute to elucidate the neurobiological mechanisms underlying psychotherapy efficacy. The inclusion of a multidisciplinary study protocol will allow to study BPD considering different features that can affect the treatment response and their reciprocal relationships. Trial registration NCT02370316. Registered 02/24/2015. Electronic supplementary material The online version of this article (10.1186/s12888-019-2127-2) contains supplementary material, which is available to authorized users.

Objective The objective of this study was to report the short- and medium-term outcome of surgeon-modified fenestrated endovascular aneurysm repair (SM-FEVAR) for acute complex aortic aneurysms. Methods Interrogation of a prospectively maintained database identified consecutive patients who underwent SM-FEVAR for acute complex aortic aneurysms (including mycotic aneurysms treated with rifampicin-soaked endografts) in a single institution between October 2009 and November 2018. Results A total of 54 patients (37 men; median age, 73 years [range, 50-85 years]; aneurysm diameter, 76 mm [interquartile range, 58-90 mm]) with acute thoracoabdominal aortic aneurysms (n = 50; 40 symptomatic, 10 ruptured; 19 extent I-III, 31 extent IV) or symptomatic type IA endoleaks after infrarenal endovascular aneurysm repair (n = 4) underwent SM-FEVAR. Seven of the patients had adjunct chimney and periscope stent grafts or surgical bypasses. A total of 187 vessels (mean, 3.4 [range, 1-5] per patient) were targeted for preservation; nine occluded intraoperatively or within 30 days. The 30-day/in-hospital mortality was 16.7% (n = 9; symptomatic, 7.4%; rupture, 50%) and fell significantly from 29.6% (n = 8) in the first 27 patients to 3.7% (n = 1) in the most recent 27 patients (P = .0243). Spinal cord ischemia occurred in one patient (1.9%) who died within 30 days. No survivors required permanent renal dialysis. Estimated survival at 12 and 24 months was 73.2% (standard error [SE], 6.2%). Eight patients underwent 12 late aorta- or graft-related reinterventions. Estimated freedom from reintervention at 12 months and 24 months was 87.9% (SE, 5.2%) and 81.6% (SE, 6.4%), respectively. Conclusions In patients with acute complex aneurysms, SM-FEVAR provides a customized solution that is associated with good medium-term survival and durability. The knowledge and skills to perform safe SM-FEVAR should be within the capabilities of high-volume specialist aortic centers.

Portal vein thrombosis (PVT) is a rare condition in the general population that develops serious complications if left untreated for long time. We present a case of a 29-year-old woman who developed PVT due to protein S deficiency versus neonatal funiculitis. Over time, the patient developed upper gastrointestinal bleeding due to esophageal varices and hypersplenism with splenic sequestration that caused minor bleeding episodes. Laparoscopic splenectomy and proximal splenorenal shunt with distal pancreatectomy due to aneurysmal dilatations of the splenic artery were successfully performed to avoid mayor progression of portal hypertension. Patient was discharged with indefinite anticoagulation and after surgery platelets raised 3 3 ectomy and proximal splenorenal shunt for portal hypertension due to portal vein ombosis is an adequate surgery procedure which should be applied in these medical cases. Portal vein thrombosis (PVT) is a rare condition in the general population that develops serious complications if left untreated for long time. We present a case of a 29-year-old woman who developed PVT due to protein S deficiency versus neonatal funiculitis. Over time, the patient developed upper gastrointestinal bleeding due to esophageal varices and hypersplenism with splenic sequestration that caused minor bleeding episodes. Laparoscopic splenectomy and proximal splenorenal shunt with distal pancreatectomy due to aneurysmal dilatations of the splenic artery were successfully performed to avoid mayor progression of portal hypertension. Patient was discharged with indefinite anticoagulation and after surgery platelets raised 3 3 ectomy and proximal splenorenal shunt for portal hypertension due to portal vein ombosis is an adequate surgery procedure which should be applied in these medical cases.

The aim of the present study was to assess the role of action observation treatment (AOT) in the rehabilitation of upper limb motor functions in children with cerebral palsy. We carried out a two-group, parallel randomized controlled trial. Eighteen children (aged 5–11 yr) entered the study: 11 were treated children, and 7 served as controls. Outcome measures were scores on two functional scales: Melbourne Assessment of Unilateral Upper Limb Function Scale (MUUL) and the Assisting Hand Assessment (AHA). We collected functional scores before treatment (T1), at the end of treatment (T2), and at two months of follow-up (T3). As compared to controls, treated children improved significantly in both scales at T2 and this improvement persisted at T3. AOT has therefore the potential to become a routine rehabilitation practice in children with CP. Twelve out of 18 enrolled children also underwent a functional magnetic resonance study at T1 and T2. As compared to controls, at T2, treated children showed stronger activation in a parieto-premotor circuit for hand-object interactions. These findings support the notion that AOT contributes to reorganize brain circuits subserving the impaired function rather than activating supplementary or vicariating ones.

Complex regional pain syndrome type I (CRPS I) is a multifactorial painful disorder with a complex pathogenesis. Both peripheral and central mechanisms are involved. Acute CRPS I is considered to be an exaggerated inflammatory disorder; however, over time, because of altered function of the sympathetic nervous system and maladaptive neuroplasticity, CRPS I evolves into a neurological disorder. This review thoroughly describes the pathophysiological aspects of CRPS I and summarizes the potential therapeutic options. The mechanisms and targets of the treatment are different in the early and late stages of the disease. This current review builds on a previous review by this author group by deepening the role of the peripheral classic and neuronal inflammatory component in the acute stage of this painful disorder. Level of Evidence Not applicable.

We suggest that preschoolers’ frequent obliviousness to the risks and opportunities of deception comes from a trusting stance supporting verbal communication. Three studies (N = 125) confirm this hypothesis. Three-year-olds can hide information from others (Study 1) and they can lie (Study 2) in simple settings. Yet when one introduces the possibility of informing others in the very same settings, three-year-olds tend to be honest (Studies 1 and 2). Similarly, four-year-olds, though capable of treating assertions as false, trust deceptive informants (Study 3). We suggest that children's reduced sensitivity to the opportunities of lying, and to the risks of being lied to might help explain their difficulties on standard false belief tasks.

Discharge planning is important to prevent surgical site infections, reduce costs, and improve the hospitalization experience. The identification of early variables that can predict a longer-than-expected length of stay or the need for a discharge with additional needs can improve this process. A cohort study was conducted in the largest hospital of Northern Italy, collecting discharge records from January 2017 to January 2020 and pre-admission visits in the last three months. Socio-demographic and clinical data were collected. Linear and logistic regression models were fitted. The main outcomes were the length of stay (LOS) and discharge destination. The main predictors of a longer LOS were the need for additional care at discharge (+10.76 days), hospitalization from the emergency department (ED) (+5.21 days), and age (+0.04 days per year), accounting for clinical variables (p &lt, 0.001 for all variables). Each year of age and hospitalization from the ED were associated with a higher probability of needing additional care at discharge (OR 1.02 and 1.77, respectively, p &lt, 0.001). No additional findings came from pre-admission forms. Discharge difficulties seem to be related mainly to age and hospitalization procedures: those factors are probably masking underlying social risk factors that do not show up in patients with planned admissions.

Maturational processes in the developing brain are disrupted by exposure to environmental toxicants, setting the stage for deviant developmental trajectories. Manganese (Mn) is an essential nutrient that is neurotoxic at high levels of exposure, particularly affecting the basal ganglia and prefrontal cortex. Both the intensity and timing of exposure matter; deciduous teeth can be used to retrospectively and objectively determine early-life windows of vulnerability. The aim of this pilot study was to examine associations between prenatal, early postnatal and childhood dentine Mn concentrations and intrinsic functional connectivity (iFC) of adolescents’ brains. 14 adolescents (12–18 years; 6 girls) from northern Italian regions with either current, historic or no Mn contamination, completed a 10-minute resting state functional Magnetic Resonance Imaging (MRI) scan in an 1.5T MRI scanner. We estimated prenatal, early postnatal and childhood Mn concentrations in deciduous teeth using laser ablation-inductively coupled plasma-mass spectrometry. We performed seed-based correlation analyses, focusing on six subcortical seeds (left and right caudate, putamen, pallidum) and one cortical seed (bilateral middle frontal gyrus) from Harvard-Oxford atlases. We examined linear and quadratic correlations between log-transformed Mn concentrations and seed-based iFC (Bonferroni-corrected p

Purpose This study assessed the acceptability and limited efficacy of a self-management intervention to improve lifestyle behaviors and headache outcomes among rural adolescents with recurrent headache. Design and methods Participants were randomly assigned to a self-management intervention for adolescent headache (SMI-AH, n = 13) or standard care group (n = 17). The SMI-AH group participated in goal-setting, self-monitoring, and information processing to modify lifestyle behaviors (missed meals, caffeine intake, and poor sleep). Independent samples t-test was used to compare the means of outcomes at baseline and 6-week follow-up between the treatment group and control group. Linear mixed model (LMM) was used to examine the intervention effects over time. Results The mean age was 14.8 years (sd = 1.6, range, 12–17); with female participants accounting for 80% of the sample (n = 24) and persons reporting white race were 97% (n = 29). The SMI-AH group demonstrated a greater magnitude of change in lifestyle behaviors, including increased days of eating breakfast and lunch. The multivariate LMM showed significant intervention effect of lunch intake (p = 0.042 with Cohen's d = 0.42) and borderline significant effect of breakfast intake (p = 0.064 with Cohen's d = 0.38). Participants reported the intervention was easy to use and helpful to monitor behaviors. Conclusions Among rural adolescents, a self-management intervention is a feasible approach for engaging youth. The SMI-AH provides an opportunity for the adolescents to talk about their behaviors and participate in goal setting as well as the plan of care with the provider. Challenges identified in this study are manageable and a full study is feasible with modifications.

Crying is the principal means by which newborn infants shape parental behavior to meet their needs. While this mechanism can be highly effective, infant crying can also be an aversive stimulus that leads to parental frustration and even abuse. Fathers have recently become more involved in direct caregiving activities in modern, developed nations, and fathers are more likely than mothers to physically abuse infants. In this study, we attempt to explain variation in the neural response to infant crying among human fathers, with the hope of identifying factors that are associated with a more or less sensitive response. We imaged brain function in 39 first-time fathers of newborn infants as they listened to both their own and a standardized unknown infant cry stimulus, as well as auditory control stimuli, and evaluated whether these neural responses were correlated with measured characteristics of fathers and infants that were hypothesized to modulate these responses. Fathers also provided subjective ratings of each cry stimulus on multiple dimensions. Fathers showed widespread activation to both own and unknown infant cries in neural systems involved in empathy and approach motivation. There was no significant difference in the neural response to the own vs. unknown infant cry, and many fathers were unable to distinguish between the two cries. Comparison of these results with previous studies in mothers revealed a high degree of similarity between first-time fathers and first-time mothers in the pattern of neural activation to newborn infant cries. Further comparisons suggested that younger infant age was associated with stronger paternal neural responses, perhaps due to hormonal or novelty effects. In our sample, older fathers found infant cries less aversive and had an attenuated response to infant crying in both the dorsal anterior cingulate cortex (dACC) and the anterior insula, suggesting that compared with younger fathers, older fathers may be better able to avoid the distress associated with empathic over-arousal in response to infant cries. A principal components analysis revealed that fathers with more negative emotional reactions to the unknown infant cry showed decreased activation in the thalamus and caudate nucleus, regions expected to promote positive parental behaviors, as well as increased activation in the hypothalamus and dorsal ACC, again suggesting that empathic over-arousal might result in negative emotional reactions to infant crying. In sum, our findings suggest that infant age, paternal age and paternal emotional reactions to infant crying all modulate the neural response of fathers to infant crying. By identifying neural correlates of variation in paternal subjective reactions to infant crying, these findings help lay the groundwork for evaluating the effectiveness of interventions designed to increase paternal sensitivity and compassion.

Background/Purpose Skin products such as shower gels have a direct impact on skin health and wellness. Although qualitative haptic characterization through explicit, verbal measures in consumer studies are often sufficient for general comparison on consumer perceived skin feel, a quantitative approach is desired to characterize minute changes in skin condition in response to various skin products. Prior research has sought to characterize the haptic properties of human skin in vitro and in vivo, but very few studies have compared the haptic effects of commercial skin products having relatively similar formulations. In addition, related studies have typically utilized simple, low-precision devices and fixtures. The purpose of this study was to use a precision magnetic levitation haptic device to characterize the frictional properties of human skin in vivo before, during, and after treatment with commercially available shower gels, to capture the entire cycle of consumer experience on skin feel. Methods A hybrid force-position control algorithm was used to control a precision magnetic levitation haptic device with silicone tactor to stroke the human skin (on the volar forearm) in vivo. Position and force data were collected from 32 human subjects using eight different commercially available shower gels, while stroking the skin before, during, and after treatment. The data were analyzed to produce coefficients of friction and viscous damping constant, which were used as metrics for comparing the effects of each shower gel type. Other factors investigated include skin test location, order, and subject age and gender. Results Results showed significant differences between the effects of eight various shower gels, especially after accounting for variance between subjects. Most notably, Shower Gel four with high level of petrolatum, along with Shower Gels five and six with low levels of castoryl maleate (a skin lipid analog), as well as Shower Gel two with high levels of vegetable oils yielded higher skin coefficients of friction 20 min after treatment, indicating higher levels of skin hydration than other shower gels without either high levels of skin beneficial agents or low levels of castoryl maleate. Conversely, Shower Gel eight treatment yielded the lowest skin coefficient of friction both immediately after rinsing and 20 min after treatment. In addition, when applied to the skin as un-lathered gels, Shower Gels six and seven with acrylate polymers yielded viscous damping constants twice that of other gels, while Shower Gel three yielded the lowest. When lathered into foam on skin, Shower Gel eight yielded the highest viscous damping constant, while Shower Gel three, along with Shower Gels one and five yielded lower values than others. Conclusion The results of this study show that different shower gels do have significant measurable differences in their effects on skin properties, and that using a high-precision haptic device can be a useful tool for quantifying the haptic properties of skin in vivo.

Antineuronal antibodies have been implicated in tic and obsessive compulsive disorders (OCD) associated with group A streptococcal infections. We investigated antineuronal autoantibody levels as well as antibody-mediated neuronal cell signaling activity, as previously reported for Sydenham chorea and pediatric autoimmune neuropsychiatric disorder associated with streptococci (PANDAS), to determine immunological profiles for a large cohort of children with tics and/or OCD.Study participants (n=311; ages 4-27 years, 66% male) were selected from a larger group of individuals with self-reported neuropsychiatric symptoms (n=742) and included only those with accurate knowledge of group A streptococcal infection status, except for four individuals in whom streptococcal infection status was unknown. Healthy control samples (n=16; ages 5-14 years, 81% male), came from the National Institute of Mental Health and Yale University. In addition to serum donations, participants and/or legal guardians provided neuropsychiatric and related medical histories of symptoms that had lasted1 year. Antineuronal immunoglobulin G (IgG) titers were measured by standard enzyme-linked immunosorbent assay (ELISA) and compared with mean titers of normal age-matched sera against lysoganglioside, tubulin, and dopamine receptors (D1R and D2R). Antibody-mediated signaling of calcium calmodulin dependent protein kinase II (CaMKII) activity in a human neuronal cell line (SK-N-SH) was tested in serum.Of 311 individuals, 222 (71%) had evidence of group A streptococcal infection, which was associated with tics and/or OCD status (p=0.0087). Sera from individuals with tics and/or OCD (n=261) had evidence of elevated serum IgG antibodies against human D1R (p0.0001) and lysoganglioside (p=0.0001), and higher serum activation of CaMKII activity (p0.0001) in a human neuronal cell line compared with healthy controls (n=16). Furthermore, patients with tics and OCD had significantly increased activation of CaMKII activity compared with patients with only tics or only OCD (p0.033 for each).Our study suggested a significant correlation of streptococcal-associated tics and OCD with elevated anti-D1R and antilysoganglioside antineuronal antibodies in serum concomitant with higher activation of CaMKII in human neuronal cells. Youth and young adults with chronic tics and OCD may have underlying infectious/immunologic etiology.

Background The independent prognostic impact of diabetes mellitus ( DM ) and prediabetes mellitus (pre‐ DM ) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐ DM on survival outcomes in the GISSI ‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial. Methods and Results We assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI ‐ HF trial, who were stratified by presence of DM (n=2852), pre‐ DM (n=2013), and non‐ DM (n=2070) at baseline. Compared with non‐ DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐ DM patients and those with pre‐ DM . Cox regression analysis showed that DM , but not pre‐ DM , was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI , 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI , 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI , 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI , 1.01–1.29, respectively). Conclusions Presence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00336336.

Background The role of serum ferritin (SF) as a prognostic factor has been analyzed in patients with myelodysplastic syndromes (MDS) who have undergone hematopoietic stem cell transplantation (HSCT), but the prognostic role of elevated SF levels is still controversial in lower risk MDS patients. Therefore, we performed a meta-analysis of all available published literature to evaluate whether elevated SF levels are associated with a worse overall survival (OS) among patients with low risk MDS. Material and methods A systematic bibliographic search of relevant studies was undertaken in accordance with guidelines for meta-analysis of observational studies in epidemiology. Electronic databases were searched through July 2016 for studies examining the level of SF as a prognostic factor in the adults affected by MDS. Results Six articles were included in the meta-analysis. A significant association between OS and SF was achieved for the threshold of SF≥1000 ng/mL, when the only study that used SF cut-off ≥2000 ng/mL was not included in the meta-analysis (RR = 1.33; 95% CI = 1.06–1.67). The estimated risk was 2.58 (95% CI = 1.41–4.74) when a SF cut-off≥500 ng/mL was considered. Conclusions Our findings underlined a worse survival in patients with MDS who had higher SF levels. The association was stronger and achieved statistical significance after stratification of analyses in which we excluded cut-offs of SF level considered as outliers. These results suggest that negative impact on OS already exist at SF level ≥500 ng/mL. Prospective studies, are needed to better understand this relationship and, above all, to clarify whether earlier iron chelation therapy could improve patients’ OS.

IntroductionAlthough there has been a decrease in the number of cases of salmonellosis in the European Union, it still represents the primary cause of foodborne outbreaks. In Calabria region, data are lacking for the incidence of human non-typhoid salmonellosis as active surveillance has never been carried out.ObjectiveTo report the results of a laboratory and patient-based morbidity survey in Calabria to describe the incidence and distribution ofSalmonellaserovars isolated from humans, with a focus on antimicrobial resistance patterns.MethodsPositive cultures from human samples were collected from every laboratory participating in the surveillance, with a minimum set of information about each isolate. A questionnaire was then administered to the patients by telephone interview to assess the potential risk exposures.Salmonellaisolates underwent biochemical identification, molecular analysis by PCR and antimicrobial susceptibility testing by the disk-diffusion method.ResultsDuring a 2-year period, 105 strains ofSalmonellaspp were isolated from samples of patients with diarrhoea, with the highest isolation rate for children aged 1–5 years. The standardised rate was 2.7 cases per 1 00 000 population. The most commonSalmonellaisolates belonged to monophasic variant ofS.Typhimurium (S.4,[5],12:i:-) (33.3%), followed byS. Typhimurium (21.9%). 30.5% of the isolates were susceptible to all microbial agents tested and the most common pan-susceptible serotype wasS.Napoli (100%).S. 4,[5],12:i:- was resistant to ampicillin, streptomycin, sulfonamides and tetracyclines in 42.9% cases, while resistance to quinolones was seen in 14.3% of the isolates.ConclusionsThe results provide evidence that an active surveillance system effectively enhancesSalmonellanotifications. The high prevalence of antimicrobial resistance, including resistance to quinolones and multiresistance, enforces the need to strengthen strategies of surveillance and monitoring of antimicrobial use.

Multiple lines of research indicate that fathers often treat boys and girls differently in ways that impact child outcomes. The complex picture that has emerged, however, is obscured by methodological challenges inherent to the study of parental caregiving, and no studies to date have examined the possibility that gender differences in observed real-world paternal behavior are related to differential paternal brain responses to male and female children. Here we compare fathers of daughters and fathers of sons in terms of naturalistically observed everyday caregiving behavior and neural responses to child picture stimuli. Compared with fathers of sons, fathers of daughters were more attentively engaged with their daughters, sang more to their daughters, used more analytical language and language related to sadness and the body with their daughters, and had a stronger neural response to their daughter's happy facial expressions in areas of the brain important for reward and emotion regulation (medial and lateral orbitofrontal cortex [OFC]). In contrast, fathers of sons engaged in more rough and tumble play (RTP), used more achievement language with their sons, and had a stronger neural response to their son's neutral facial expressions in the medial OFC (mOFC). Whereas the mOFC response to happy faces was negatively related to RTP, the mOFC response to neutral faces was positively related to RTP, specifically for fathers of boys. These results indicate that real-world paternal behavior and brain function differ as a function of child gender. (PsycINFO Database Record

This study investigates paternal brain function with the hope of better understanding the neural basis for variation in caregiving involvement among men. The neuropeptides oxytocin (OT) and vasopressin (AVP) are implicated in paternal caregiving in humans and other species. In a double-blind, placebo-controlled, within-subject pharmaco-functional MRI experiment, we randomized 30 fathers of 1–2 year old children to receive either 24 IU intranasal OT before one scan and placebo before the other scan (n = 15) or 20 IU intranasal AVP before one scan and placebo before the other scan (n = 15). Brain function was measured with fMRI as the fathers viewed pictures of their children, unknown children and unknown adults, and as they listened to unknown infant cry stimuli. Intranasal OT, but not AVP, significantly increased the BOLD fMRI response to viewing pictures of own children within the caudate nucleus, a target of midbrain dopamine projections, as well as the dorsal anterior cingulate (dACC) and visual cortex, suggesting that intranasal oxytocin augments activation in brain regions involved in reward, empathy and attention in human fathers. OT effects also varied as a function of order of administration such that when OT was given before placebo, it increased activation within several reward-related structures (substantia nigra, ventral tegmental area, putamen) more than when it was given after placebo. Neither OT nor AVP had significant main effects on the neural response to cries. Our findings suggest that the hormonal changes associated with the transition to fatherhood are likely to facilitate increased approach motivation and empathy for children, and call for future research that evaluates the potential of OT to normalize deficits in paternal motivation, as might be found among men suffering from post-partum depression.

Objective To evaluate left-sided and right-sided heart echocardiographic results after restrictive mitral annuloplasty in chronic ischemic mitral regurgitation. Methods Left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction, left ventricular indexed mass, coaptation depth, transmitral mean gradient, systolic pulmonary arterial pressure, tricuspid annular plane systolic excursion, right ventricular ejection fraction, and tricuspid insufficiency grading were evaluated preoperatively, postoperatively, at 6 months, and at the end of the follow-up period in 64 patients undergoing restrictive mitral annuloplasty and coronary artery bypass grafting. Recurrence of chronic ischemic mitral regurgitation was defined as 2+/4+ grade or greater mitral regurgitation at any time postoperatively. Results Twenty-two months of freedom from recurrent chronic ischemic mitral regurgitation was 58.2% ± 9.8%. Recurrent chronic ischemic mitral regurgitation did not lead to reverse remodeling of left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and ventricular indexed mass ( P = not significant), with increased coaptation depth, parallel to follow-up chronic ischemic mitral regurgitation worsening. Effective restrictive mitral annuloplasty induced reverse remodeling of left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and ventricular indexed mass, improved left ventricular ejection fraction, shortened coaptation depth, and improved mean gradient ( P ≤ .014). Recurrent chronic ischemic mitral regurgitation in patients without tricuspid surgery prevented improvements of systolic pulmonary arterial pressure, tricuspid annular plane systolic excursion, right ventricular ejection fraction, worsening New York Heart Association ( P = .003), and daily diuretic need ( P = .008), whereas effective restrictive mitral annuloplasty progressively improved tricuspid insufficiency grading, systolic pulmonary arterial pressure, right ventricular ejection fraction, tricuspid annular plane systolic excursion, New York Heart Association, and diuretic need ( P ≤ .013). Patients undergoing tricuspid annuloplasty did not show any improvement of systolic pulmonary arterial pressure, right ventricular ejection fraction, and tricuspid annular plane systolic excursion regardless of the recurrence of chronic ischemic mitral regurgitation ( P = not significant), although effective restrictive mitral annuloplasty improved tricuspid insufficiency grading, New York Heart Association, and daily diuretic need ( P ≤ .010). Conclusion Effective restrictive mitral annuloplasty induces reverse left ventricular remodeling. Absence of recurrent chronic ischemic mitral regurgitation improves tricuspid insufficiency grading, systolic pulmonary arterial pressure, right ventricular ejection fraction, tricuspid annular plane systolic excursion, New York Heart Association, and diuretic need in patients who do not undergo tricuspid surgery, but only tricuspid insufficiency grading, New York Heart Association, and daily diuretic need in patients who undergo tricuspid surgery.

Patients undergoing cardiac surgery require adequate myocardial protection. Manipulating myocardial metabolism may improve the extent of myocardial protection. Perhexiline has been shown to be an effective anti-anginal agent due to its metabolic modulation properties by inhibiting the uptake of free fatty acids into the mitochondrion, and thereby promoting a more efficient carbohydrate-driven myocardial metabolism. Metabolic modulation may augment myocardial protection, particularly in patients with left ventricular hypertrophy (LVH) known to have a deranged metabolic state and are at risk of poor postoperative outcomes. This study aimed to evaluate the role of perhexiline as an adjunct in myocardial protection in patients with LVH secondary to aortic stenosis (AS), undergoing an aortic valve replacement (AVR).In a multicentre double-blind randomized controlled trial of patients with AS undergoing AVR ± coronary artery bypass graft surgery, patients were randomized to preoperative oral therapy with either perhexiline or placebo. The primary end point was incidence of inotrope use to improve haemodynamic performance due to a low cardiac output state during the first 6 h of reperfusion, judged by a blinded end points committee. Secondary outcome measures included haemodynamic measurements, electrocardiographic and biochemical markers of new myocardial injury and clinical safety outcome measures.The trial was halted early on the advice of the Data Safety and Monitoring Board. Sixty-two patients were randomized to perhexiline and 65 to placebo. Of these, 112 (54 perhexiline and 48 placebo) patients received the intervention, remained in the trial at the time of the operation and were analysed. Of 110 patients who achieved the primary end point, 30 patients (16 perhexiline and 14 placebo) had inotropes started appropriately; there was no difference in the incidence of inotrope usage OR of 1.65 [confidence interval (CI): 0.67-4.06] P = 0.28. There was no difference in myocardial injury as evidenced by electrocardiogram odds ratio (OR) of 0.36 (CI: 0.07-1.97) P = 0.24 or postoperative troponin release. Gross secondary outcome measures were comparable between the groups.Perhexiline as a metabolic modulator to enhance standard myocardial protection does not provide an additional benefit in haemodynamic performance or attenuate myocardial injury in the hypertrophied heart secondary to AS. The role of perhexiline in cardiac surgery is limited.

Aim Late failure of bioprosthetic valves may limit their use in patients Methods Patients who underwent aortic valve replacement with or without coronary artery bypass grafting between July 1997 and January 2010 with Carbomedics supraannular Top Hat valves were identified. Details of readmissions and late deaths were obtained from the National Hospital Episodes Statistics data and the Office of National Statistics, tracked by the Quality and Outcomes Research Unit. Late complications associated with this prosthesis were evaluated. Results Of 253 patients identified, 181 underwent isolated aortic valve replacement and 72 had aortic valve replacement with coronary artery bypass grafting. The 30-day mortality was 1.6%, and 5- and 10-year survival rates were 91.4% and 80.5%, respectively. Detailed readmission data were available after 2001 ( n = 170). Two (1.2%) patients required reoperation for endocarditis and pannus formation. Of the 17 late deaths in this subset, 4 were attributable to cardiac causes. One patient was treated for heart failure, and 2 developed bleeding complications. Conclusions Implantation of the Carbomedics Top Hat supraannular valve in our unit resulted in satisfactory in-hospital and midterm survival with low incidences of endocarditis and late heart failure.

The aim of this study was to evaluate the diagnostic accuracy of postnatal multidetector computed tomography (MDCT) compared with prenatal ultrasound (US), surgical findings, and histology, in 33 patients with congenital cystic lung disease.Thirty-three patients, 17 males and 16 females, were evaluated by MDCT. Twenty-seven of these patients underwent prenatal US between week 18 and 22, and between week 32 and 35 of gestation. Lung lobectomy, segmentectomy, atypical resection, lesion resection were performed in 31 patients and surgical specimens were analysed.Prenatal US and MDCT correctly diagnosed 76.9 and 94 % of the lesions, respectively. Disagreement occurred in six lesions with prenatal US and in two lesions with MDCT. No statistically significant differences were observed between the two techniques (P = 0.122).As most surgeons consider the surgical resection of these lesions mandatory, our study underscores the essential role of imaging, in particular CT, in providing invaluable preoperative information on congenital cystic lung diseases recognised in uterus.