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Background: The indications for pediatric airway endoscopy are expanding and a variety of therapeutic interventions are feasible for central airway obstruction (CAO) and other central airway pathologies, apart from foreign body removal., Methods: In this retrospective chart review from four centers, we describe the indications, procedures, outcomes, and complications of therapeutic bronchoscopic interventions in children for non foreign-body removal indications., Results: A total of 72 children (mean age:140 [60.4] months) underwent 143 therapeutic bronchoscopic airway interventions under general anesthesia, via a rigid or flexible bronchoscope or both, between January 2015 and November 2023. 67 (93%) had CAO. The most common diagnoses were posttubercular tracheobronchial stenosis (29%) followed by central airway tumor (26%) and postintubation/posttracheostomy tracheal stenosis (26%). Airway stenosis (subglottic/tracheal/bronchial) was the commonest bronchoscopic finding (43 [59.7%]) followed by endoluminal growth/mass (21 [29.2%]). The most frequently performed procedure was airway dilatation (38, 52.7%), using balloon dilators (89.5%) or rigid bronchoscope (10.5%). Endoluminal tumor debulking was performed in 21 (29%). Assistive modalities included electrocautery (44%), mechanical debulking (10%), cryotherapy (10%), or laser (4%). Airway stent insertion alone or in combination with airway dilatation or debulking was performed in 24 (33.3%) children. The airway conduit used was supraglottic airway in 19 (26%) and rigid bronchoscope in 53 (74%) children. Immediate procedural success was observed in 66 (92%) patients. Fourteen (19.4%) patients had minor procedural complications. Thirty-three (46%) children required a repeat bronchoscopic procedure., Conclusion: Like adults, multimodality therapeutic bronchoscopic airway interventions are feasible and safe in children for CAO and other central airway indications., (© 2024 Wiley Periodicals LLC.)

Background: Psychological and social support for adolescents living with HIV remains undocumented and unaddressed in Central Africa. This study aimed at assessing effectiveness of a peer-facilitated community-based support model in improving retention in care among adolescents living with HIV and attending care in Chantal Biya Foundation, Yaounde, Cameroon., Materials and Methods: We conducted an analysis of adolescents aged 10-19 years old, perinatally infected with HIV, on follow-up in the Day Care Unit of a reference hospital in Yaounde, Cameroon, and enrolled in the IAS-CIPHER-2021/1214-ATE-SMAVI, a individually randomized controlled trial. While the control arm only received routine care in the health facility, the intervention arm, in addition, was assigned to an HIV association for sustained support model, including support groups, leisure workshops and home visits. Structured questionnaires, including validated French versions of mental health scales, were quarterly administered to the study participants in both study arms by trained healthcare providers. The main outcome was maintaining retention in care beyond the first 15-month period of the study start. Kaplan-Meier and Cox regression models were fitted to assess association between intervention and outcome. Hazard Ratio (HR) across categories of exposure variables were compared using Wald's test. p-value <0.05 was considered significant., Results: In total, 305 adolescents were recruited in the study at a median age of 15.2 years old, including 162 (53.1 %) females and 153 individuals in the intervention arm. Mental health troubles were prevalent: severe depression (26.9 %), high or very high anxiety (28.9 %), and low self-esteem (84.9 %). Noteworthy, all of the baseline characteristics were balanced irrelevant to the study arm. Probability of maintaining good retention in care beyond the first 15-month period of study start remained higher in the intervention arm (82.0 % [95 %CI: 73.7 %-88.4 %]) versus the control arm (71.0 % [95 %CI: 63.2 %-78.1 %]), [cHR (95 %CI): 2.0 (1.1-3.3), p=0.044]., Conclusions: Capacity should be built in terms of implementing community-based peer-facilitated support groups in local organizations providing care to adolescents living with HIV., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Mass gathering event restrictions were part of mitigation measures during the COVID-19 pandemic that were lifted as prevalence decreased and after vaccination rollout. We explored SARS-CoV-2 antigen rapid diagnostic test acceptability and positivity in community settings in Cameroon. In August-October 2022, community workers sensitized and referred individuals for COVID-19 testing to nearby testing points in Douala and Yaoundé. Participants consented to SARS-CoV-2 antigen rapid diagnostic testing, a survey, or both components. We describe the positivity rate, COVID-19-related history, and Likert-scale testing perceptions. Factors associated with testing acceptance were analyzed using logistic regression. Overall, 20.5% (2,449/11,945) of sensitized individuals visited testing points, and 1,864 (76.1%) were enrolled; 50.6% accepted the survey and testing (46.0% accepted survey only). Seven (0.7%) of 1,006 individuals tested positive. Most (71.8%; 1,292/1,800) considered community testing more accessible than hospital-based testing. Individuals accepting versus refusing testing differed in perceived COVID-19 risk (67%, 49%; P <0.001), belief in accurate test results (79%, 47%; P <0.001), and ability to test easily (96%, 55%; P <0.001). Males (adjusted odds ratio [aOR]: 1.26 [1.04-1.53]) and those over 50 years (aOR: 1.9 [1.4-2.7]), with symptoms (aOR: 1.80 [1.30-2.50]), and at least partial vaccination (aOR: 0.76 [0.58-0.99]) were significantly associated with test acceptance. Refusal reasons included lack of perceived need for testing (33.8%) and testing discomfort (26.3%). Although community-based testing was generally perceived as important, actual testing uptake was low. In future pandemics, community testing should be optimized by addressing misinformation, offering alternative testing modalities for greater comfort, creating demand, and tailoring approaches to maximize testing uptake.

Background: Contact tracing was described as a key strategy to contribute to controlling the spread of severe acute respiratory syndrome of Coronavirus 2 (SARS-CoV-2) but implementing it can be a challenge. Digitalisation of contact tracing is among the proposed solutions being explored in sub-Saharan African settings. We assessed the effectiveness of a digital tool to expand SARS-CoV-2 testing in exposed individuals in Cameroon., Methods: We conducted a cluster-randomised (1:1) trial in eight health districts, including 22 facilities and SARS-CoV-2 testing units, randomly assigned to a digital (intervention) or standard (control) contact tracing approach. The intervention consisted of a contact tracing module added to the digital platform "Mamal PRO" used for monitoring and coordination of Coronavirus Disease 2019 pandemic response in Cameroon. The primary outcome was the proportion of contacts declared by SAR-CoV-2 index patients who were successfully traced and tested for SARS-CoV-2 evaluated with a Poisson regression model with cluster adjustment. This study is registered with ClinicalTrials.gov (NCT05684887)., Findings: Between October 18, 2022, and March 31, 2023, we enrolled 164 index patients in the intervention arm and 149 in the control arm, who identified 854 and 849 contacts, respectively. In the intervention arm, 93.8% (801/854) of identified contacts were successfully reached by the tracing unit versus 54.5% (463/849) in the control arm. The intervention significantly increased the likelihood of successfully tracing contacts (adjusted relative risks (RR) 1.72 [95% CI: 1.00-2.95], p = 0.049). The median (interquartile range, IQR) time to successfully tracing contacts was 0 days [IQR: 0, 1] in the intervention and 1 day [IQR: 0, 2] in the control arm. In the intervention arm, 21.3% (182/854) of identified contacts received SARS-CoV-2 testing compared to 14.5% (123/849) in the control arm (adjusted RR 1.47 [95% CI: 0.44-4.90], p = 0.530)., Interpretation: Digitalising the contact tracing process improved exposure notification and facilitated the tracing of a greater number of contacts of individuals infected with SARS-CoV-2 in resource-limited settings., Funding: The study was funded by FIND, United Kingdom (FCDO 40105983), Switzerland (81066910), Netherlands (SDD 4000004160), Canada (DFATD 7429348), The Kingdom of Saudi Arabia (FIND-ACT-A DX PARTNERSHIP 20.08.2020), The Rockefeller Foundation (2020 HTH 059), Germany (BMZ Covid-19 Diagnostic and Surveillance Response 27.07.2021), Australia (DFAT 76442), Kuwait (M239/2020), The Government of Portugal and Partners (ANF, BCP, CGF, APIFARMA) and The BlackRock Foundation (Grant Agreement as of April 20, 2022)., Competing Interests: BKT has received support from FIND (through funding for the AFCON grant paid to his institution) to participate to a meeting on operational research in Kigali and the CPHIA conference. All other authors declared no competing interests to disclose., (© 2024 The Author(s).)

Introduction: People living with HIV are considered at higher risk of developing severe forms of tuberculosis (TB) disease. Providing HIV testing to TB-exposed people is therefore critical. We present the results of integrating HIV testing into a community-based intervention for household TB contact management in Cameroon and Uganda., Methods: Trained community health workers visited the households of index patients with TB identified in 3 urban/semiurban and 6 rural districts or subdistricts as part of a cluster-randomized trial and provided TB screening to all household contacts. Voluntary HIV counseling and testing were offered to contacts aged 5 years or older with unknown HIV status. We describe the cascade of care for HIV testing and the factors associated with the acceptance of HIV testing., Results: Overall, 1983 household contacts aged 5 years or older were screened for TB. Of these contacts, 1652 (83.3%) did not know their HIV status, 1457 (88.2%) accepted HIV testing, and 1439 (98.8%) received testing. HIV testing acceptance was lower among adults than children [adjusted odds ratio (aOR) = 0.35, 95% confidence interval (CI): 0.22 to 0.55], those living in household of an HIV-positive vs HIV-negative index case (aOR = 0.56, 95% CI: 0.38 to 0.83), and contacts requiring a reassessment visit after the initial TB screening visit vs asymptomatic contacts (aOR = 0.20, 95% CI: 0.06 to 0.67) and was higher if living in Uganda vs Cameroon (aOR = 4.54, 95% CI: 1.17 to 17.62) or if another contact of the same index case was tested for HIV (aOR = 9.22, 95% CI: 5.25 to 16.18)., Conclusion: HIV testing can be integrated into community-based household TB contact screening and is well-accepted., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Perinatally HIV-Infected Adolescents (HIVIA) are more likely to have mental health problems than their uninfected peers. In resource-limited settings, mental health disorders are rarely taken into account in the care offered to HIVIA and have an impact on their routine follow-up. The objective of this study was to assess the baseline socio-demographic factors and mental health conditions associated with detectable viral load or poor ART adherence in HIVIA on ART followed at the Mother and Child Centre of the Chantal Biya Foundation in Yaoundé (CME-FCB), Cameroon., Methods: A cross-sectional study was conducted in HIVIA aged 10 to 19 years, followed at CME-FCB during the period from December 2021 to March 2022. Sociodemographic, clinical, and mental characteristics were collected using a structured questionnaire administered face-to-face by trained healthcare providers. The primary outcome was viral load ≥ 40 copies/mL in HIVIA on ART for at least six months. The secondary outcome was poor ART adherence, defined as ≥ 1 missed dose of antiretroviral therapy within the last past three days. The main exposure variables were mental health disorders, including the level of anxiety, depression and low self-esteem., Results: In total, 302 adolescents were interviewed, 159 (52.7 %) were girls and median age was 15.2 years (IQR: 12.0-17.5). Having missed at least 1 dose of ART drugs during the last 3 days before screening concerned 53 (35.0 %) cases. Of the 247 adolescents with an available viral load (VL) in the last 12 months prior to screening, 33 (26.7 %) had a VL ≥ 40 copies/mL. Among participating adolescents, 29.1 % presented with high or very high anxiety, 26.5 % with severe depression, 36.4 % with history of suicidal ideation, and 20.5 % low self-esteem. Low self-esteem was strongly associated with a higher risk of poor ART adherence (adjusted odds ratio(aOR) (95 % confidence interval (95 %CI)): 2.2 (1.1-4.3); p = 0.022). Living with the father (aOR (95 %CI): 0.6 (0.3-1.1); p = 0.085) or in a household with a televisor (aOR (95 %CI): 0.5 (0.2-1.1); p = 0.069) were slightly associated with a lower risk of poor adherence to ART. Having both parents alive (aOR (95 %CI): 0.4 (0.2-0.9); p = 0.031) or receiving ART with efavirenz or dolutegravir (aOR (95 %CI): 0.5 (0.2-0.9); p = 0.047) was strongly associated with a lower likelihood of having a detectable VL. Moreover, detectable viral load was slightly less frequent in adolescents whose household was equipped with a television (p = 0.084) or who were completely disclosed for HIV status (p = 0.070)., Conclusion: This study found that co-morbid low self-esteem had higher odds of poor ART adherence in HIVIA. Moreover, both poor ART adherence, and detectable viral load were associated with impaired life conditions in HIVIA., Competing Interests: Declaration of competing interest The authors declare there is no conflict of interests., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Introduction: A subset of autistic children excel at word decoding but have difficulty with reading comprehension (i.e., the discrepant poor comprehender reading profile ). Prior research suggests the Visualizing and Verbalizing (V/V) for language comprehension and thinking intervention helps improve reading comprehension in autistic children with this reading profile. Previous studies have demonstrated the role of vocabulary, memory, and social functioning in reading comprehension; however, predictors and moderators of reading comprehension within this specific profile of autistic readers have not been thoroughly explored., Methods: In this study, we examined the effectiveness of the V/V intervention by comparing reading comprehension scores between groups and across time. Participants included a sample of autistic children (AUT-EXP; n=22) and a waitlist control group of autistic children (AUT-WLC; n=17) with reading comprehension difficulties, as well as a sample of non-autistic children (Non-AUT; n=26) (all age 8-13 years). AUT-EXP and AUT-WLC groups completed a battery of cognitive assessments during pre and post tests. We also analyzed whether cognitive assessment scores predicted reading comprehension, and examined the moderating effects of group (AUT-EXP vs. AUT-WLC) on these relationships., Results: The AUT-EXP group significantly improved in their pre to post reading comprehension scores ( t (21)=4.19, p <.001, d =.89), whereas the AUT-WLC group did not. Verbal memory significantly predicted reading comprehension, though group did not moderate relationships between cognitive test performance and reading comprehension., Discussion: Results suggest that the V/V intervention may help improve reading comprehension for autistic children with the discrepant poor comprehender reading profile. Additionally, strategies for improving verbal memory may indirectly enhance reading comprehension in autistic children with this reading profile., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Beckerson, Paisley, Murdaugh, Holm, Lemelman, Spencer, O’Kelley and Kana.)

Introduction: Many individuals with Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) often experience difficulty with driving, including difficulty with obtaining a driver's license as well as driving safely and efficiently. Such difficulties negatively impact their ability to function independently and participate in daily activities that require driving. ASD and ADHD commonly occur co-morbidly and share many overlapping clinical features. Few studies have directly compared the nature of difficulties in driving safety outcomes between ASD and ADHD. The overarching goal of the current study was to characterize and compare self-reported driving behavior among young autistic drivers, ADHD drivers, and typically developing (TD) drivers., Method: Fifty-four participants (14 ASD, 20 ADHD, 20 TD); ages 16-30) completed the Autism Spectrum Quotient and ADHD Adult Rating scale as a method of screening of symptoms. All three groups then completed the Driving Behavior Questionnaire (DBQ), which measured self-reported driving violations, driving errors, and overall risky driving behavior. The three groups of ASD, ADHD, and TD individuals were then compared regarding symptomology and driving behavior differences., Results: One-way ANOVAs indicated group differences in DBQ total scores and DBQ errors. Drivers with ADHD reported significantly greater overall risky driving behaviors and driving errors compared to ASD and TD drivers. There were no significant differences between ASD and TD drivers in reported risky driving behaviors and errors. Linear regressions indicated that among all drivers, self-reported ADHD symptoms were significantly associated with higher levels of self-reported overall risky driving and driving errors, regardless of diagnostic group., Discussion: Risky driving and driving errors may be more closely related to symptoms that are characteristic of ADHD. This has implications for individuals with ADHD and autistic individuals who often show or report higher rates of ADHD symptoms. Future studies should compare driving skills of ASD and ADHD drivers using objective measures of driving performance, such as driving simulators or on-road tests., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study aimed at investigating the biohydrogen and biomethane potential of co-digestion from palm oil mill effluent (POME) and concentrated latex wastewater (CLW) in a two-stage anaerobic digestion (AD) process under thermophilic (55 ± 3 °C) and at an ambient temperature (30 ± 3 °C) conditions, respectively. The batch experiments of POME:CLW mixing ratios of 100:0, 70:30, 50:50, 30:70, and 0:100 was investigated with the initial loadings at 10 g-VS/L. The highest hydrogen yield of 115.57 mLH 2 /g-VS was obtained from the POME: CLW mixing ratio of 100:0 with 29.0 of C/N ratio. While, the highest subsequent methane production yield of 558.01 mLCH 4 /g-VS was achieved from hydrogen effluent from POME:CLW mixing ratio of 70:30 0 with 21.8 of C/N ratio. This mixing ratio revealed the highest synergisms of about 9.21% and received maximum total energy of 19.70 kJ/g-VS. Additionally, continuous hydrogen and methane production were subsequently performed in a series of continuous stirred tank reactor (CSTR) and up-flow anaerobic sludge blanket reactor (UASB) to treat the co-substate. The results indicated that the highest hydrogen yield of POME:CLW mixing ratio at 70:30 of 95.45 mL-H 2 /g-VS was generated at 7-day HRT, while methane production was obtained from HRT 15 days with a yield of 204.52 mL-CH 4 /g-VS. Thus, the study indicated that biogas production yield of CLW could be enhanced by co-digesting with POME. In addition, the two-stage AD model under anaerobic digestion model no. 1 (ADM-1) framework was established, 9.10% and 2.43% of error fitting of hydrogen and methane gas between model simulation data and experimental data were found. Hence, this research work presents a novel approach for optimization and feasibility for co-digestion of POME with CLW to generate mixed gaseous biofuel potentially., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Autism spectrum disorder (ASD) is characterized by difficulties in theory of mind (ToM) and social communication. Studying structural and functional correlates of ToM in the brain and how autistic and nonautistic groups differ in terms of these correlates can help with diagnosis and understanding the biological mechanisms of ASD. In this study, we investigated white matter volume (WMV) and gray matter volume (GMV) differences between matching autistic and nonautistic samples, and how these structural features relate to age and ToM skills, indexed by the Reading the Mind in the Eyes (RMIE) measure. The results showed widespread GMV and WMV differences between the two groups in regions crucial for social processes. The autistic group did not express the typically observed negative GMV and positive WMV correlations with age at the same level as the nonautistic group, pointing to abnormalities in developmental structural changes. In addition, we found differences between the two groups in how GMV relates to ToM, particularly in the left frontal regions, and how WMV relates to ToM, mostly in the cingulate and corpus callosum. Finally, GMV in the left insula, a region that is part of the salience network, was found to be crucial in distinguishing ToM performance between the two groups., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose of Review: Autistic adults frequently require treatment of mental health problems. Increased rates of suicidality and diminished quality of life among autistic people may be partially attributable to psychiatric symptoms. Some risk factors for mental health problems in autistic people are likely the same as risk factors present in neurotypical individuals, but unique factors that are specific to neurodivergent individuals, and some even more specific to autistic people, may exist. Understanding pathways from autism to mental health problems could inform intervention efforts at the individual and societal levels., Recent Findings: We review a growing body of research identifying risk processes across the affective, cognitive, and social domains. Consistent with the principle of equifinality, different processes appear to independently and jointly lead to heightened risk for the onset of mental health problems. Autistic adults frequently utilize mental healthcare services, and experience heightened risk for chronic impairment as a result of mental health problems. Understanding causal and developmental risk processes in autism should inform personalized treatment. We synthesize extant research on these processes and offer suggestions for addressing them therapeutically and societally., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Adolescents living with HIV are more likely to experience mental health challenges compared to their peers who do not have HIV. However, there is a lack of data regarding the mental health of adolescents living with HIV in Cameroon. Understanding risk factors and protective factors that influence mental health amongst adolescents is critical for effective programming. The purpose of this study was to estimate the prevalence and the factors associated with depression in adolescents infected with HIV and receiving ART in a Cameroonian referral hospital., Methods: This was a cross-sectional study which enrolled adolescents perinatally infected with HIV, aged 10-19 years, on antiretroviral treatment and cared for at "Centre Mère et Enfant de la Fondation Chantal Biya", Yaounde, Cameroon. Structured questionnaires, including validated French versions of the Coopersmith Child Depression Inventory (CDI), the Multidimensional Anxiety Scale for Children (MASC) and the Coopersmith Self Esteem Inventory (SEI), were administered to the study participants by the healthcare providers., Results: All in all, 302 adolescents were recruited in the study at a median age of 15.2 years (interquartile range : 12.0 - 17.5), including 159 (52.7 %) girls. Both parents had died for 57 (18.9 %) adolescents ; only the father was alive for 64 (21.2 %) ; only the mother was alive for 48 (15.9 %), both parents were alive for 133 (44.0 %). This study found prevalence of 26.5 % for severe depression, 36.4 % for suicidal ideation, 29.1 % for high/very high anxiety, and 20.5 % for low self-esteem. No factor was found significantly associated with severe depression but there was a trend towards decreased risk of severe depression among adolescents whose mother was alive [OR= 0.4 (0.1-1.0), p = 0.084]., Conclusion: This study found that elevated depression, anxiety, and low self-esteem symptoms were prevalent among Cameroonian adolescents perinatally infected with HIV. Services and systems should go beyond clinical management of HIV and address the psychosocial and mental health of adolescents. The indicators of mental health among adolescents infected with HIV should be included in HIV program reporting., Competing Interests: Competing interests The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Objective: To develop a diagnostic algorithm for cystic fibrosis (CF) in the setting of unavailability of sweat chloride, based on clinical features and basic laboratory investigations., Methods: In a prospective observational study, we enrolled children with recurrent/persistent pneumonia with either malabsorption or poor growth, undergoing a sweat chloride test, between January 2019 and December 2020. They were simultaneously evaluated for aquagenic wrinkling of hands, stool fat globules, sputum for bacterial culture, blood gas, and serum electrolytes. Sensitivity and specificity were calculated for parameters having a significant difference between CF and non-CF groups. Scoring systems and algorithms for the diagnosis of CF were developed., Results: Of 134 children enrolled, 46 (34%) had CF. The sensitivity and specificity of various parameters to diagnose CF was: sibling death due to respiratory illness (30.43%, 96.59%), aquagenic wrinkling (76.74%, 47.67%), metabolic alkalosis (17.78%, 94.12%), hyponatremia (28.89%, 89.41%), stool fat globules (38.46%, 81.18%), and presence of Pseudomonas in sputum culture (23.68%, 98.80%). Using coefficients of significant parameters on stepwise logistic regression, the composite score for diagnosis of CF was calculated as: 3X sibling death due to respiratory illness + 1.5X hyponatremia + 1.5X metabolic alkalosis + 1.5X aquagenic wrinkling + 1X stool fat globules + 2.5X presence of Pseudomonas in sputum culture (each of the variables scores 0 or 1 for absence and presence, respectively). The cut-off of ≥2.5 had sensitivity and specificity of 81.82% and 76.83%, respectively., Conclusions: In resource-limited settings, the proposed diagnostic algorithm can be used for the diagnosis of presumptive CF with fair sensitivity and specificity., (© 2022 Wiley Periodicals LLC.)

Individuals with attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) may exhibit driving difficulties due to cognitive impairments such as time perception difficulties, a construct related to the perception of time-to-collision (TTC). This study examined the timing abilities of drivers with ASD and ADHD. Sixty participants (n ADHD  = 20, n ASD  = 20, n TD  = 20) completed a time reproduction task and a TTC estimation task in a driving simulator. Results indicated drivers with ASD were less precise in time reproduction across all time intervals and over-reproduced time at shorter intervals. Drivers with ASD produced larger TTC estimates when driving at a faster speed compared to typically developing drivers. Drivers with ASD, but not ADHD, appear to present difficulties in time estimation abilities., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: We aimed to describe the clinical profile and risk factors for severe disease in adolescents hospitalised with coronavirus disease 2019 (COVID-19)., Methods: A retrospective analysis of an admitted cohort of COVID-19 patients was performed at a tertiary hospital in North India. Adolescents aged 12-18 years who were hospitalised during the first wave (March-December, 2020) and the second wave (March-June, 2021) were included. Data on the demographic details, clinical presentation, laboratory parameters, disease severity at admission, treatments received, and in-hospital outcomes were retrieved., Results: The study included 197 adolescents with a median [inter-quartile range (IQR)] age of 15 (13-17) years, of whom 117 (59.4%) were male. Among these, 170 (86.3%) were admitted during the first wave. Underlying co-morbidities were present in nine (4.6%) patients. A total of 60 (30.9%) patients were asymptomatic. In the severity grading, 148 (84.6%) had mild, 16 (9.1%) had moderate, and 11 (6.3%) had severe disease. Fever (14.9%) and cough (14.9%) were the most commonly encountered symptoms. The median (IQR) duration of hospital stay was 10 (8-13) days, and six (3.1%) patients died in the hospital., Conclusion: Adolescents admitted with COVID-19 had predominantly asymptomatic or mild disease, and the mortality rate was 3.1%., Competing Interests: None

Background: Acute bronchiolitis is one of the most frequent causes of emergency department visits and hospitalisation in children up to three years of age. There is no specific treatment for bronchiolitis except for supportive treatment, which includes ensuring adequate hydration and oxygen supplementation. Continuous positive airway pressure (CPAP) aims to widen the lungs' peripheral airways, enabling deflation of overdistended lungs in bronchiolitis. Increased airway pressure also prevents the collapse of poorly supported peripheral small airways during expiration. Observational studies report that CPAP is beneficial for children with acute bronchiolitis. This is an update of a review first published in 2015 and updated in 2019., Objectives: To assess the efficacy and safety of CPAP compared to no CPAP or sham CPAP in infants and children up to three years of age with acute bronchiolitis., Search Methods: We conducted searches of CENTRAL (2021, Issue 7), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE (1946 to August 2021), Embase (1974 to August 2021), CINAHL (1981 to August 2021), and LILACS (1982 to August 2021) in August 2021. We also searched the US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for completed and ongoing trials on 26 October 2021., Selection Criteria: We considered randomised controlled trials (RCTs), quasi-RCTs, cross-over RCTs, and cluster-RCTs evaluating the effect of CPAP in children with acute bronchiolitis., Data Collection and Analysis: Two review authors independently assessed study eligibility, extracted data using a structured pro forma, analysed data, and performed meta-analyses. We used the Cochrane risk of bias tool to assess risk of bias in the included studies. We created a summary of the findings table employing GRADEpro GDT software.  MAIN RESULTS: We included three studies with a total of 122 children (62/60 in intervention/control arms) aged up to 12 months investigating nasal CPAP compared with supportive (or 'standard') therapy. We included one new trial (72 children) in the 2019 update that contributed data to the assessment of respiratory rate and the need for mechanical ventilation for this update. We did not identify any new trials for inclusion in the current update. The included studies were single-centre trials conducted in France, the UK, and India. Two studies were parallel-group RCTs, and one study was a cross-over RCT. The evidence provided by the included studies was of low certainty; we made an assessment of high risk of bias for blinding, incomplete outcome data, and selective reporting, and confidence intervals were wide. The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to risk of bias and imprecision around the effect estimate (risk difference -0.01, 95% confidence interval (CI) -0.09 to 0.08; 3 RCTs, 122 children; low certainty evidence). None of the trials measured time to recovery. Limited, low certainty evidence indicated that CPAP decreased respiratory rate (decreased respiratory rate is better) (mean difference (MD) -3.81, 95% CI -5.78 to -1.84; 2 RCTs, 91 children; low certainty evidence). Only one trial measured change in arterial oxygen saturation (increased oxygen saturation is better), and the results were imprecise (MD -1.70%, 95% CI -3.76 to 0.36; 1 RCT, 19 children; low certainty evidence). The effect of CPAP on change in arterial partial carbon dioxide pressure (pCO₂) (decrease in pCO₂ is better) was imprecise (MD -2.62 mmHg, 95% CI -5.29 to 0.05; 2 RCTs, 50 children; low certainty evidence). Duration of hospital stay was similar in both the CPAP and supportive care groups (MD 0.07 days, 95% CI -0.36 to 0.50; 2 RCTs, 50 children; low certainty evidence). Two studies did not report pneumothorax, but pneumothorax did not occur in one study. No studies reported occurrences of deaths. Several outcomes (change in partial oxygen pressure, hospital admission rate (from the emergency department to hospital), duration of emergency department stay, and need for intensive care unit admission) were not reported in the included studies., Authors' Conclusions: The use of CPAP did not reduce the need for mechanical ventilation in children with bronchiolitis, although the evidence was of low certainty. Limited, low certainty evidence suggests that breathing improved (a decreased respiratory rate) in children with bronchiolitis who received CPAP; this finding is unchanged from the 2015 review and 2019 update. Due to the limited available evidence, the effect of CPAP in children with acute bronchiolitis is uncertain for our other outcomes. Larger, adequately powered trials are needed to evaluate the effect of CPAP for children with acute bronchiolitis., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Aim: To estimate acute gastrointestinal injury (AGI) in critically ill children and association of its severity with mortality., Methods: In a prospective cohort study, critically ill children (1 month-18 years) were enrolled. Gastrointestinal symptoms over the first week of admission were classified into AGI grades 1 through 4, using a paediatric adaptation of European Society of Intensive Care Medicine AGI definitions. Performance of AGI grades in predicting 28-day mortality was evaluated., Results: Of 151 children enrolled, 71 (47%, 95% confidence interval (CI): 38.9-55.3%) developed AGI, with AGI grades 1, 2, 3 and 4 in 22.5%, 15.9%, 6.6% and 2%, respectively. The 28-day mortality progressively increased with AGI grade 0 (15%), 1 (35%), 2 (50%), 3 (70%), through 4 (100%), P < 0.001. Association of AGI grades with 28-day mortality was significant even after adjustment for disease severity, age and nutritional status (odds ratio (OR) = 2.152, 95% CI: 1.455, 3.184). Among AGI grades, and paediatric logistic organ dysfunction-2 score components, cardiovascular (OR = 1.525, 95% CI: 1.142, 2.037) and haematological (OR = 1.719, 95% CI: 1.067, 2.772) components of paediatric logistic organ dysfunction-2 score and AGI grades (OR = 1.565, 95% CI: 1.001, 2.449) showed significant association with 28-day mortality., Conclusions: Nearly half of the critically ill children developed AGI. AGI grades were independently associated with increased mortality, and mortality progressively increased with AGI grade., (© 2021 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Background: There is a lack of studies on cystic fibrosis (CF) outcomes in children from developing countries like India. Identifying risk factors for mortality may help identify the high-risk group and plan policy management of such patients. We aimed to determine the factors associated with mortality among Indian children with CF., Methods: In this retrospective study, we extracted demography, clinical features, laboratory and outcome data from medical records of children with CF. Bivariate and multivariate analysis was performed to identify variables associated with mortality., Results: We enrolled 178 children, and there were 32 (18.0%) deaths. Median (IQR) z-score for body mass index (BMI) at last follow up was -1.5 (-2.7, -0.2) and -2.5 (-4.0, -1.6), p-value 0.039, in survived and deceased group respectively. Mean (SD) of % predicted of FEV1/FVC and FEV1 25-75 at the time of diagnosis in survived versus diseased group was 94.7 (24.1) versus 81.5 (19.1), p-value 0.063 and 56.1 (38.9) versus 45.7 (29.9), p-value 0.347, respectively. Significant factors associated with mortality included history of neonatal complications; hazard ratio (HR): 8.5 (95% confidence interval [CI]: 3.0-23.9, p < 0.001), low Z-scores for BMI at the time of diagnosis; HR: 7.1 (95% CI: 2.3-22.0, p < 0.001), FEV1/FVC at the time of diagnosis; HR: 5.1 (95% CI: 1.65-15.4, p < 0.004), and FEV1 25-75; HR: 3.6 (95% CI: 1.1-11.8, p = 0.03)., Conclusions: Factors associated with increased mortality risk included neonatal complications, low BMI, and lower pulmonary function test results. Low BMI and low PFT indices can be improved upon by timely treatment of respiratory infections, better nutrition, early diagnosis, and treatment. A newborn screening program may help in early diagnosis and identification of the neonatal problem of CF., (© 2021 Wiley Periodicals LLC.)

Alzheimer's disease (AD) is the leading cause of dementia and has received considerable research attention, including using neuroimaging biomarkers to classify patients and/or predict disease progression. Generalized linear models, e.g., logistic regression, can be used as classifiers, but since the spatial measurements are correlated and often outnumber subjects, penalized and/or Bayesian models will be identifiable, while classical models often will not. Many useful models, e.g., the elastic net and spike-and-slab lasso, perform automatic variable selection, which removes extraneous predictors and reduces model variance, but neither model exploits spatial information in selecting variables. Spatial information can be incorporated into variable selection by placing intrinsic autoregressive priors on the logit probabilities of inclusion within a spike-and-slab elastic net framework. We demonstrate the ability of this framework to improve classification performance by using cortical thickness and tau-PET images from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to classify subjects as cognitively normal or having dementia, and by using a simulation study to examine model performance using finer resolution images., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Justin M. Leach, Lloyd J. Edwards, Rajesh Kana, Kristina Visscher, and Nengjun Yi have no conflicts to declare. Inmaculada Aban has received funding and lists the following as possible conflicts of interests: Myasthenia Gravis Foundation of America (MGFA), Ra Pharmaceutical through MGFA, Alexion through MGFA, Argenx through MGFA, Catalyst through MGFA, Verona Pharmaceutical. No patents, products in development or marketed products associated with this research need to be declared. No information here alters our adherence to policies on sharing data and materials.

Background: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review., Objectives: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis., Search Methods: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 09 September 2021. We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 16 August 2021., Selection Criteria: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis., Data Collection and Analysis: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager., Main Results: Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively., Authors' Conclusions: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Bronchoalveolar lavage (BAL) via flexible bronchoscopy is a valuable diagnostic technique in children. The quality of BAL is directly related to the volume of the fluid recovered. Continuous wall suctioning and handheld syringe suctioning are the 2 commonly used methods, but they are rarely compared in children. We aimed to compare the above 2 suctioning techniques for BAL in the pediatric age group., Methods: This randomized controlled study enrolled children from 1 month to 18 years of age undergoing flexible bronchoscopy and BAL. We compared continuous wall suctioning and the handheld syringe suctioning technique. The primary outcome was the percentage of BAL fluid recovery in 2 different suctioning techniques. Secondary outcomes included technical acceptable BAL and yield of various diagnostic tests in BAL., Results: The study included 73 children (48 boys) with a median (interquartile range) age of 30 (8, 108) months. There were 37 children in the wall mount group and 36 children in the syringe suction group. Baseline characteristics of the groups were similar. The wall mount suction had more recovery of BAL fluid compared with the syringe method (43.6±8.4% vs. 37.8±8.5%, P=0.004). The proportion of BAL having a fluid recovery of ≥40% was also high in the wall mount suction [31 (83.8%) vs. 17 (47.2%); P=0.001]. There was no difference in diagnostic yield between the groups., Conclusion: Wall mount suction had better BAL fluid recovery compared with handheld syringe suction in children undergoing flexible bronchoscopy. The diagnostic yield was similar in both groups., Competing Interests: Disclosure: There is no conflict of interest or other disclosures., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: The extent of diaphragmatic atrophy and dysfunction in critically ill children from developing countries is not established., Objectives: To estimate changes in ultrasound measurements of diaphragmatic thickness over the first week of mechanical ventilation. To assess magnitude and risk factors of diaphragmatic atrophy., Methods: In an observational cohort study, children aged 1-18 years, requiring mechanical ventilation were included. Ultrasound measurements of diaphragmatic thickness at end-expiration (DTe) and end-inspiration (DTi), and diaphragmatic thickening fraction (DTF) were performed daily during the first week of admission, and pre- and post-extubation. Diaphragmatic atrophy (%) and atrophy rate (rate of decline in DTe, % per day) were calculated., Measurements and Main Results: Of 55 children (74.6% boys) enrolled, 20 (36.4%) died. Of 35 children with planned extubation, 5 (14.3%) required reintubation. Baseline median (interquartile range [IQR]) DTe, DTi, and DTF were 1.27 mm (1, 1.6), 1.76 mm (1.35, 2.10), and 33.75% (26.90, 44.60), respectively. There was a significant reduction in DTe over the first week of mechanical ventilation (p < .001), median (IQR) diaphragmatic atrophy and atrophy rate of 9.91% (5.26, 17.35) and 2.01% (1.08, 3.04) per day, respectively. Diaphragmatic atrophy rate was lower in pressure targeted ventilation (n = 44; 1.79% [1.03, 2.87]) than volume targeted ventilation (n = 11; 3.10% [1.31, 5.49]), p = .038. There was no difference in diaphragmatic parameters (atrophy rate, and peri-extubation DTe and DTF) in extubation success versus failure., Conclusions: The diaphragm undergoes progressive atrophy during the first week of mechanical ventilation in critically ill children. Future studies should evaluate ventilation strategies to reduce the diaphragmatic atrophy., (© 2020 Wiley Periodicals LLC.)

Entomophthoromycosis is a rare fungal infection of the skin and subcutaneous tissue occurring predominantly in tropical and subtropical regions. In children, it mostly affects the lower half of the body. With this, we report a case of Entomophthoromycosis in a 6-year-old girl who presented late with extensive involvement of the upper half of the body. She responded well to treatment with potassium iodide and itraconazole. We also reviewed cases of Entomophthoromycosis reported in children.

Background: In the recent years, machine learning algorithms have been more widely and increasingly applied in biomedical fields. In particular, their application has been drawing more attention in the field of psychiatry, for instance, as diagnostic tests/tools for autism spectrum disorder (ASD). However, given their complexity and potential clinical implications, there is an ongoing need for further research on their accuracy., Objective: This study aimed to perform a systematic review and meta-analysis to summarize the available evidence for the accuracy of machine learning algorithms in diagnosing ASD., Methods: The following databases were searched on November 28, 2018: MEDLINE, EMBASE, CINAHL Complete (with Open Dissertations), PsycINFO, and Institute of Electrical and Electronics Engineers Xplore Digital Library. Studies that used a machine learning algorithm partially or fully for distinguishing individuals with ASD from control subjects and provided accuracy measures were included in our analysis. The bivariate random effects model was applied to the pooled data in a meta-analysis. A subgroup analysis was used to investigate and resolve the source of heterogeneity between studies. True-positive, false-positive, false-negative, and true-negative values from individual studies were used to calculate the pooled sensitivity and specificity values, draw Summary Receiver Operating Characteristics curves, and obtain the area under the curve (AUC) and partial AUC (pAUC)., Results: A total of 43 studies were included for the final analysis, of which a meta-analysis was performed on 40 studies (53 samples with 12,128 participants). A structural magnetic resonance imaging (sMRI) subgroup meta-analysis (12 samples with 1776 participants) showed a sensitivity of 0.83 (95% CI 0.76-0.89), a specificity of 0.84 (95% CI 0.74-0.91), and AUC/pAUC of 0.90/0.83. A functional magnetic resonance imaging/deep neural network subgroup meta-analysis (5 samples with 1345 participants) showed a sensitivity of 0.69 (95% CI 0.62-0.75), specificity of 0.66 (95% CI 0.61-0.70), and AUC/pAUC of 0.71/0.67., Conclusions: The accuracy of machine learning algorithms for diagnosis of ASD was considered acceptable by few accuracy measures only in cases of sMRI use; however, given the many limitations indicated in our study, further well-designed studies are warranted to extend the potential use of machine learning algorithms to clinical settings., Trial Registration: PROSPERO CRD42018117779; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=117779., (©Sun Jae Moon, Jinseub Hwang, Rajesh Kana, John Torous, Jung Won Kim. Originally published in JMIR Mental Health (http://mental.jmir.org), 20.12.2019.)

Rationale: A variety of inhaled antigens have been implicated to cause hypersensitivity pneumonitis (HP). We observed that children force-fed with lentil-based weaning food had persistent respiratory symptoms and radiology similar to HP., Objectives: To describe the clinical features of lentil HP., Methods: We conducted a retrospective review of records of children with lentil HP attending Pediatric Chest Clinic at a tertiary care hospital in North India from 2008-2018. We included case records with elevated immunoglobulin G (IgG) specific for lentil antigen., Measurements and Main Results: Nine children (seven boys) were identified with median (IQR) age of onset of symptoms and diagnosis at 9 (6, 12) and 11 (10, 16) months, respectively. Chronic cough (100%), shortness of breath (89%), fever (78%), vomiting (56%), and wheezing (33%) were common symptoms. Fine crackles were heard in 33% of children, none had clubbing. CT scans showed nodular opacities and consolidation in 78% and 67% children, respectively. Bronchoalveolar lavage showed increased neutrophils and lymphocytes (67% and 33%, respectively). All children showed rapid remission with systemic steroids (prednisolone), starting at a median dose of 1 (1, 1.1) mg kg -1  day -1 . One child had a clinical relapse which was treated with oral steroids again. IgG specific to lentil antigens was elevated in children with lentil HP (21->200 mgA/L) compared with children with other chronic respiratory illnesses (n = 7, <2-11.4 mgA/L)., Conclusions: Lentil aspiration is an important cause of HP in infants of weaning age with force-feeding practices. Further studies are needed to identify aspirated antigens which cause HP in aspiration prone children., (© 2019 Wiley Periodicals, Inc.)

Background: Acute bronchiolitis is one of the most frequent causes of emergency department visits and hospitalisation in children. There is no specific treatment for bronchiolitis except for supportive treatment, which includes ensuring adequate hydration and oxygen supplementation. Continuous positive airway pressure (CPAP) aims to widen the lungs' peripheral airways, enabling deflation of overdistended lungs in bronchiolitis. Increased airway pressure also prevents the collapse of poorly supported peripheral small airways during expiration. Observational studies report that CPAP is beneficial for children with acute bronchiolitis. This is an update of a review first published in 2015., Objectives: To assess the efficacy and safety of CPAP compared to no CPAP or sham CPAP in infants and children up to three years of age with acute bronchiolitis., Search Methods: We conducted searches of CENTRAL (2017, Issue 12), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1946 to December, 2017), Embase (1974 to December 2017), CINAHL (1981 to December 2017), and LILACS (1982 to December 2017) in January 2018., Selection Criteria: We considered randomised controlled trials (RCTs), quasi-RCTs, cross-over RCTs, and cluster-RCTs evaluating the effect of CPAP in children with acute bronchiolitis., Data Collection and Analysis: Two review authors independently assessed study eligibility, extracted data using a structured pro forma, analysed data, and performed meta-analyses., Main Results: We included three studies with a total of 122 children (62/60 in intervention/control arms) aged up to 12 months that investigated nasal CPAP compared with supportive (or "standard") therapy. We included one new trial (72 children) that contributed data to the assessment of respiratory rate and need for mechanical ventilation for this update. The included studies were single-centre trials conducted in France, the UK, and India. Two studies were parallel-group RCTs and one was a cross-over RCT. The evidence provided by the included studies was low quality; we assessed high risk of bias for blinding, incomplete outcome data, and selective reporting, and confidence intervals were wide.The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to imprecision around the effect estimate (3 RCTs, 122 children; risk ratio (RR) 0.69, 95% confidence interval (CI) 0.14 to 3.36; low-quality evidence). None of the trials measured time to recovery. Limited, low-quality evidence indicated that CPAP decreased respiratory rate (2 RCTs, 91 children; mean difference (MD) -3.81, 95% CI -5.78 to -1.84). Only one trial measured change in arterial oxygen saturation, and the results were imprecise (19 children; MD -1.70%, 95% CI -3.76 to 0.36). The effect of CPAP on change in arterial partial carbon dioxide pressure (pCO₂) was imprecise (2 RCTs, 50 children; MD -2.62 mmHg, 95% CI -5.29 to 0.05; low-quality evidence). Duration of hospital stay was similar in both CPAP and supportive care groups (2 RCTs, 50 children; MD 0.07 days, 95% CI -0.36 to 0.50; low-quality evidence). Two studies did not report about pneumothorax, but pneumothorax did not occur in one study. No studies reported occurrences of deaths. Several outcomes (change in partial oxygen pressure, hospital admission rate (from emergency department to hospital), duration of emergency department stay, and need for intensive care unit admission) were not reported in the included studies., Authors' Conclusions: Limited, low-quality evidence suggests that breathing improved (a decreased respiratory rate) in children with bronchiolitis who received CPAP; this finding is unchanged from the 2015 review. Further evidence for this outcome was provided by the inclusion of a low-quality study for the 2018 update. Due to the limited available evidence, the effect of CPAP in children with acute bronchiolitis is uncertain for other outcomes. Larger, adequately powered trials are needed to evaluate the effect of CPAP for children with acute bronchiolitis.

Photoprotective non-photochemical quenching (NPQ) represents an effective way to dissipate the light energy absorbed in excess by most phototrophs. It is often claimed that NPQ formation/relaxation kinetics are determined by xanthophyll composition. We, however, found that, for the alveolate alga Chromera velia, this is not the case. In the present paper, we investigated the reasons for the constitutive high rate of quenching displayed by the alga by comparing its light harvesting strategies with those of a model phototroph, the land plant Spinacia oleracea. Experimental results and in silico studies support the idea that fast quenching is due not to xanthophylls, but to intrinsic properties of the Chromera light harvesting complex (CLH) protein, related to amino acid composition and protein folding. The pKa for CLH quenching was shifted by 0.5 units to a higher pH compared with higher plant antennas (light harvesting complex II; LHCII). We conclude that, whilst higher plant LHCIIs are better suited for light harvesting, CLHs are 'natural quenchers' ready to switch into a dissipative state. We propose that organisms with antenna proteins intrinsically more sensitive to protons, such as C. velia, carry a relatively high concentration of violaxanthin to improve their light harvesting. In contrast, higher plants need less violaxanthin per chlorophyll because LHCII proteins are more efficient light harvesters and instead require co-factors such as zeaxanthin and PsbS to accelerate and enhance quenching.

Background: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review., Objectives: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis., Search Methods: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 29 September 2017.We searched two ongoing trial registries (Clinicaltrials.gov and the WHO trials platform). Date of latest search: 24 January 2018., Selection Criteria: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis., Data Collection and Analysis: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager., Main Results: Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively., Authors' Conclusions: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Children with neurodevelopmental disorders benefit most from early interventions and treatments. The development and validation of brain-based biomarkers to aid in objective diagnosis can facilitate this important clinical aim. The objective of this review is to provide an overview of current progress in the use of neuroimaging to identify brain-based biomarkers for autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD), two prevalent neurodevelopmental disorders. We summarize empirical work that has laid the foundation for using neuroimaging to objectively quantify brain structure and function in ways that are beginning to be used in biomarker development, noting limitations of the data currently available. The most successful machine learning methods that have been developed and applied to date are discussed. Overall, there is increasing evidence that specific features (for example, functional connectivity, gray matter volume) of brain regions comprising the salience and default mode networks can be used to discriminate ASD from typical development. Brain regions contributing to successful discrimination of ADHD from typical development appear to be more widespread, however there is initial evidence that features derived from frontal and cerebellar regions are most informative for classification. The identification of brain-based biomarkers for ASD and ADHD could potentially assist in objective diagnosis, monitoring of treatment response and prediction of outcomes for children with these neurodevelopmental disorders. At present, however, the field has yet to identify reliable and reproducible biomarkers for these disorders, and must address issues related to clinical heterogeneity, methodological standardization and cross-site validation before further progress can be achieved.

Background: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis. This is an updated version of the review., Objectives: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis., Search Methods: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 27 July 2015.We searched the ongoing trial registry clinicaltrials.gov for any ongoing trials. Latest search for clinicaltrials.gov: 23 October 2015., Selection Criteria: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis., Data Collection and Analysis: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager., Main Results: Only one study enrolling 14 participants was eligible for inclusion in the review. The double-blind study compared a daily dose of 600 mg omalizumab or placebo along with twice daily itraconazole and oral corticosteroids, with a maximum daily dose of 400 mg. Treatment lasted six months but the study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit participants into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) participants in omalizumab group and placebo group respectively., Authors' Conclusions: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled studies of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Background: Bronchiolitis is one of the most frequent causes of respiratory failure in infants; some infants will require intensive care and mechanical ventilation. There is lack of evidence regarding effective treatment for bronchiolitis other than supportive care. Abnormalities of surfactant quantity or quality (or both) have been observed in severe cases of bronchiolitis. Exogenous surfactant administration appears to favourably change the haemodynamics of the lungs and may be a potentially promising therapy for severe bronchiolitis. This is an update of a review published in Issue 9, 2012. We did not identify any new studies for inclusion, and our conclusions remain unchanged., Objectives: To evaluate the efficacy of exogenous surfactant administration (i.e. intratracheal administration of surfactant of any type (whether animal-derived or synthetic), at any dose and at any time after start of ventilation) compared to placebo, no intervention or standard care in reducing mortality and the duration of ventilation in infants and children with bronchiolitis requiring mechanical ventilation., Search Methods: We searched the Cochrane Central Register of Controlled Studies (CENTRAL; 2015, Issue 5) which contains the Cochrane Acute Respiratory Infections Group's Specialised Register; MEDLINE (1948 to June week 3, 2015); EMBASE (1974 to June 2015); CINAHL (1982 to June 2015); LILACS (1985 to June 2015); and Web of Science (1985 to June 2015)., Selection Criteria: We considered prospective, randomised controlled trials (RCTs) and quasi-RCTs evaluating the effect of exogenous surfactant in infants and children with bronchiolitis requiring mechanical ventilation., Data Collection and Analysis: Two review authors selected studies independently. We extracted the data using a predefined proforma, independently analysed the data, and performed meta-analyses., Main Results: We included three small RCTs enrolling 79 participants. Two trials did not use a placebo in the control arms and the third trial used air placebo. Two included studies reported no mortality. We judged all three of the included studies to be at low risk or unclear risk across all risk of bias categories; we did not judge any of the studies to be at high risk of bias in any category. Our pooled analysis of the three trials revealed that duration of mechanical ventilation was not significantly different between the groups (mean difference (MD) -63.04, 95% confidence interval (CI) -130.43 to 4.35 hours) but duration of intensive care unit (ICU) stay was less in the surfactant group compared to the control group: MD -3.31, 95% CI -6.38 to -0.25 days. After excluding one trial which produced significant heterogeneity, the duration of mechanical ventilation and duration of ICU stay were significantly lower in the surfactant group compared to the control group: MD -28.99, 95% CI -40.10 to -17.87 hours; and MD -1.81, 95% CI -2.42 to -1.19 days, respectively. Use of surfactant had favourable effects on oxygenation and CO2 elimination. No adverse effects and no complications were observed in any of the three included studies. The level of evidence for duration of mechanical ventilation, duration of intensive care unit stay, oxygenation parameters, and carbon dioxide parameters was of moderate quality., Authors' Conclusions: Use of surfactant had favourable effects on duration of mechanical ventilation, duration of ICU stay, oxygenation, and CO2 elimination. However, the studies are few and small (n = 79) so available evidence is insufficient to establish the effectiveness of surfactant therapy for bronchiolitis in critically ill infants who require mechanical ventilation. There is a need for larger trials with adequate power and a cost-effectiveness analysis to evaluate the effectiveness of exogenous surfactant therapy for infants with bronchiolitis who require intensive care management.

Effective visual memory encoding, a function important for everyday functioning, relies on episodic and semantic memory processes. In patients with medial temporal lobe epilepsy (MTLE), memory deficits are common as the structures typically involved in seizure generation are also involved in acquisition, maintenance, and retrieval of episodic memories. In this study, we used group independent component analysis (GICA) combined with Granger causality analysis to investigate the neuronal networks involved in visual memory encoding during a complex fMRI scene-encoding task in patients with left MTLE (LMTLE; N=28) and in patients with right MTLE (RMTLE; N=18). Additionally, we built models of memory encoding in LMTLE and RMTLE and compared them with a model of healthy memory encoding (Nenert et al., 2014). For those with LMTLE, we identified and retained for further analyses and model generation 7 ICA task-related components that were attributed to four different networks: the frontal and posterior components of the DMN, visual network, auditory-insular network, and an "other" network. For those with RMTLE, ICA produced 9 task-related components that were attributed to the somatosensory and cerebellar networks in addition to the same networks as in patients with LMTLE. Granger causality analysis revealed group differences in causality relations within the visual memory network and MTLE-related deviations from normal network function. Our results demonstrate differences in the networks for visual memory encoding between those with LMTLE and those with RMTLE. Consistent with previous studies, the organization of memory encoding is dependent on laterality of seizure focus and may be mediated by functional reorganization in chronic epilepsy. These differences may underlie the observed differences in memory abilities between patients with LMTLE and patients with RMTLE and highlight the modulating effects of epilepsy on the network for memory encoding., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Acute bronchiolitis is one of the most frequent causes of emergency department visits and hospitalisation in infants. There is no specific treatment for bronchiolitis except for supportive therapy. Continuous positive airway pressure (CPAP) is supposed to widen the peripheral airways of the lung, allowing deflation of over-distended lungs in bronchiolitis. The increase in airway pressure also prevents the collapse of poorly supported peripheral small airways during expiration. In observational studies, CPAP is found to be beneficial in acute bronchiolitis., Objectives: To assess the efficacy and safety of CPAP compared to no CPAP or sham CPAP in infants and children up to three years of age with acute bronchiolitis., Search Methods: We searched CENTRAL (2014, Issue 3), MEDLINE (1946 to April week 2, 2014), EMBASE (1974 to April 2014), CINAHL (1981 to April 2014) and LILACS (1982 to April 2014)., Selection Criteria: We considered randomised controlled trials (RCTs), quasi-RCTS, cross-over RCTs and cluster-RCTs evaluating the effect of CPAP in children with acute bronchiolitis., Data Collection and Analysis: Two review authors independently assessed study eligibility, extracted data using a structured proforma, analysed the data and performed meta-analyses., Main Results: We included two studies with a total of 50 participants under 12 months of age. In one study there was a high risk of bias for incomplete outcome data and selective reporting, and both studies had an unclear risk of bias for several domains including random sequence generation. The effect of CPAP on the need for mechanical ventilation in children with acute bronchiolitis was uncertain due to imprecision around the effect estimate (two RCTs, 50 participants; risk ratio (RR) 0.19, 95% CI 0.01 to 3.63; low quality evidence). Neither trial measured our other primary outcome of time to recovery. One trial found that CPAP significantly improved respiratory rate compared with no CPAP (one RCT, 19 participants; mean difference (MD) -5.70 breaths per minute, 95% CI -9.30 to -2.10), although the other study reported no difference between groups with no numerical data to pool. Change in arterial oxygen saturation was measured in only one trial and the results were imprecise (one RCT, 19 participants; MD -1.70%, 95% CI -3.76 to 0.36). The effect of CPAP on the change in partial pressure of carbon dioxide (pCO2) was also imprecise (two RCTs, 50 participants; MD -2.62 mmHg, 95% CI -5.29 to 0.05; low quality evidence). Duration of hospital stay was similar in both of the groups (two RCTs, 50 participants; MD 0.07 days, 95% CI -0.36 to 0.50; low quality evidence). Both trials reported no cases of pneumothorax and there were no deaths in either study. Change in partial pressure of oxygen (pO2), hospital admission rate (from emergency department to hospital), duration of emergency department stay, need for intensive care unit admission, local nasal effects and shock were not measured in either study., Authors' Conclusions: The effect of CPAP in children with acute bronchiolitis is uncertain due to the limited evidence available. Larger trials with adequate power are needed to evaluate the effect of CPAP in children with acute bronchiolitis.

Background: Cystic fibrosis is an autosomal recessive multisystem disorder with an approximate prevalence of 1 in 3500 live births. Allergic bronchopulmonary aspergillosis is a lung disease caused by aspergillus-induced hypersensitivity with a prevalence of 2% to 15% in people with cystic fibrosis. The mainstay of treatment includes corticosteroids and itraconazole. The treatment with corticosteroids for prolonged periods of time, or repeatedly for exacerbations of allergic bronchopulmonary aspergillosis, may lead to many adverse effects. The monoclonal anti-IgE antibody, omalizumab, has improved asthma control in severely allergic asthmatics. The drug is given as a subcutaneous injection every two to four weeks. Since allergic bronchopulmonary aspergillosis is also a condition resulting from hypersensitivity to specific allergens, as in asthma, it may be a candidate for therapy using anti-IgE antibodies. Therefore, anti-IgE therapy, using agents like omalizumab, may be a potential therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis., Objectives: To evaluate the efficacy and adverse effects of anti-IgE therapy for allergic bronchopulmonary aspergillosis in people with cystic fibrosis., Search Methods: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Last search: 21 January 2013.We searched the ongoing trial registry clinicaltrials.gov for any ongoing trials. Latest search for clinicaltrials.gov: 22 February 2013., Selection Criteria: Randomized and quasi-randomized controlled trials comparing anti-IgE therapy to placebo or other therapies for allergic bronchopulmonary aspergillosis in people with cystic fibrosis., Data Collection and Analysis: Two review authors independently extracted data and assessed the risk of bias in the included study. They planned to perform data analysis using Review Manager 5.1., Main Results: Only one trial enrolling 14 patients was eligible for inclusion in the review. The study was terminated prematurely and complete data were not available. We contacted the study investigator and were told that the study was terminated due to the inability to recruit patients into the study despite all reasonable attempts. One or more serious side effects were encountered in six out of nine (66.67%) and one out of five (20%) patients in omalizumab group and placebo group respectively., Authors' Conclusions: There is lack of evidence for the efficacy and safety of anti-IgE (omalizumab) therapy in patients with cystic fibrosis and allergic bronchopulmonary aspergillosis. There is a need for large prospective randomized controlled trials of anti-IgE therapy in people with cystic fibrosis and allergic bronchopulmonary aspergillosis with both clinical and laboratory outcome measures such as steroid requirement, allergic bronchopulmonary aspergillosis exacerbations and lung function.

Allergic bronchopulmonary aspergillosis (ABPA), as a complication of asthma, is rare in children. The persistent and poorly-controlled asthma leading to cor pulmonale is not uncommon in adults but rarely described in the pediatric age group. Here, we report a case of asthma and ABPA complicated by pulmonary thrombo-embolism and cor pulmonale. To the best of our knowledge, such association has never been reported in the pediatric age group.

Background: Asthma is the most common chronic disease in children, and children with asthma frequently visit the paediatric emergency departments with acute exacerbations. Some of these children fail to respond to standard therapy (aerosol beta(2)-agonist with or without aerosol anticholinergic and oral or parenteral corticosteroids) for acute asthma leading to prolonged emergency department stay, hospitalisation, morbidity (e.g. barotrauma, intubation) and death, albeit rarely. Ketamine may relieve bronchospasm and is a potentially promising therapy for children with acute asthma who fail to respond to standard treatment., Objectives: To evaluate the efficacy of ketamine compared to placebo, no intervention or standard care for management of severe acute asthma in children who had not responded to standard therapy., Search Methods: We identified trials from the Cochrane Airways Group Specialised Register of trials (CAGR) and ClinicalTrials.gov. We reviewed reference lists of all primary studies and review articles for additional references. We contacted authors of identified trials and asked them to identify other published and unpublished studies. The latest search was in July 2012., Selection Criteria: Randomised controlled trials comparing ketamine to placebo or standard care in children (up to 18 years of age) presenting with an acute asthma exacerbation who had not responded to standard therapy., Data Collection and Analysis: Two review authors independently selected studies. The data were extracted in pre-defined proforma and were analysed independently by two review authors. The data analysis was performed using Review Manager 5.1., Main Results: A single study enrolling 68 non-intubated children was found eligible for inclusion in review. The study had low or unclear risk of bias. It demonstrated no significant difference in respiratory rate, oxygen saturation, hospital admission rate (odds ratio (OR) 0.77; 95% confidence interval (CI) 0.23 to 2.58) and need for mechanical ventilation between ketamine (0.2 mg/kg intravenous bolus over one to two minutes, followed by a 0.5 mg/kg per hour continuous infusion for two hours) and placebo group. There were no significant side effects of ketamine in the study. There was also no difference in need for other adjuvant therapy (OR 2.19; 95% CI 0.19 to 25.40) and in Pulmonary Index Score (mean difference (MD) -0.40; 95% CI -1.21 to 0.41) between the groups., Authors' Conclusions: The single study on non-intubated children with severe acute asthma did not show significant benefit and does not support the case studies and observational reports showing benefits of ketamine in both non-ventilated and ventilated children. There were no significant side effects of ketamine. We could not find any trials on ventilated children. To prove that ketamine is an effective treatment for acute asthma in children, there is need for sufficiently powered randomised trials of high methodological quality with objective outcome measures of clinical importance. Future trials should also explore different doses of ketamine and its role in children needing ventilation because of severe acute asthma.

Background: Bronchiolitis is one of the most frequent causes of respiratory failure in infants; some infants will require intensive care and mechanical ventilation. There is lack of evidence regarding effective treatment for bronchiolitis other than supportive care. Abnormalities of surfactant quantity or quality (or both) have been observed in severe cases of bronchiolitis. Exogenous surfactant administration appears to favourably change the haemodynamics of the lungs and may be a potentially promising therapy for severe bronchiolitis. , Objectives: To evaluate the efficacy of exogenous surfactant administration (i.e. intratracheal administration of surfactant of any type (whether animal-derived or synthetic), at any dose and at any time after start of ventilation) compared to placebo, no intervention or standard care in reducing mortality and the duration of ventilation in infants and children with bronchiolitis requiring mechanical ventilation., Search Methods: We searched CENTRAL 2012, Issue 4 which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1948 to May week 1, 2012), EMBASE (1974 to May 2012), CINAHL (1982 to May 2012), LILACS (1985 to May 2012) and Web of Science (1985 to May 2012)., Selection Criteria: We considered prospective, randomised controlled trials (RCTs) and quasi-RCTs evaluating the effect of exogenous surfactant in infants and children with bronchiolitis requiring mechanical ventilation., Data Collection and Analysis: Two review authors selected studies independently. We extracted the data using a predefined proforma, independently analysed the data and performed meta-analyses., Main Results: We included three small RCTs enrolling 79 participants. Two trials did not use a placebo in the control arms and the third trial used air placebo. Two included studies did not describe mortality. We judged some of the included studies to have an unclear risk of bias but none of the included studies had a high risk of bias. Our pooled analysis of the three trials revealed that duration of mechanical ventilation was not different between the groups (mean difference (MD) -63.04, 95% confidence interval (CI) -130.43 to 4.35 hours) but duration of intensive care unit (ICU) stay was less in the surfactant group compared to the control group: MD -3.31 (95% CI -6.38 to -0.25 days). After excluding one trial which produced significant heterogeneity, the duration of mechanical ventilation and duration of ICU stay were significantly lower in the surfactant group compared to the control group: MD -28.99 (95% CI -40.10 to -17.87 hours) and MD -1.81 (95% CI -2.42 to -1.19 days), respectively. Use of surfactant had favourable effects on oxygenation and CO(2) elimination. No adverse effects and no complications were observed in any of the three included studies., Authors' Conclusions: The available evidence is insufficient to establish the effectiveness of surfactant therapy for bronchiolitis in critically ill infants who require mechanical ventilation. There is a need for larger trials with adequate power and a cost-effectiveness analysis to evaluate the effectiveness of exogenous surfactant therapy for infants with bronchiolitis who require intensive care management.

Plants protect themselves against excessive light by the induction of Delta pH-dependent nonphotochemical quenching (qE) that is associated with de-epoxidation of violaxanthin (V) to zeaxanthin (Z) in thylakoid membranes. In this work, we report that low light (12 micromol photons m(-2) s(-1)) is sufficient for a marked stimulation of the V to Z conversion in shortly preheated wheat leaves (5 min, 40 degrees C), but without a substantial increase in qE. Re-irradiation of these leaves with high light led to a rapid induction of nonphotochemical quenching, implying a potential photoprotective role of low-light-induced Z in preheated leaves. On the contrary to low light conditions, preheated leaves exposed to high light behaved similar to nonheated leaves with respect to the V to Z conversion and qE induction. The obtained results indicate that low-light-induced lumen acidification in preheated leaves is high enough to activate V de-epoxidation, but not sufficiently high to induce the formation of quenching centers.

Objective: To assess the efficacy and safety of fluticasone propionate administered using OptiNose's novel delivery device (Opt-FP) in subjects with bilateral mild-to-moderate nasal polyposis., Methods: A prospective, multicentre, randomized, double-blind, placebo-controlled, parallel group study was conducted in adult subjects (n = 109) with mild-to-moderate bilateral nasal polyposis. Subjects received Opt-FP 400 microg or placebo twice daily for 12 weeks. Endpoints included endoscopic assessment of polyp size using Lildholdt's Scale, peak nasal inspiratory flow (PNIF), symptom scores and use of rescue medication., Results: The proportion of subjects with improvement in summed polyp score >or= 1 (Lildholdt\'s Scale) was significantly higher with Opt-FP compared with placebo at 4, 8 and 12 weeks (22% vs 7%, p = 0.011, 43% vs 7%, p < 0.001, 57% vs 9%, p < 0.001). After 12 weeks the summed polyp score was reduced by 35% (-0.98 vs +0.23, p < 0.001). PNIF increased progressively during Opt-FP treatment (p < 0.05). Combined symptom score, nasal blockage, discomfort, rhinitis symptoms and sense of smell were all significantly improved. Rescue medication use was lower (3.1% vs 22.4%, p < 0.001). Opt-FP was well tolerated., Conclusions: Fluticasone propionate (400 microg b.i.d.) administered using OptiNose's breath actuated bi-directional delivery device was an effective and well tolerated treatment for mild-to- moderate bilateral nasal polyposis.

We present here three-dimensional time-wavelength-intensity displays of changes in variable fluorescence, during the O(JI)PSMT transient, observed in cyanobacterium at room temperature. We were able to measure contributions of individual chromophores to fluorescence spectra at various times of fluorescence induction (FI). The method was applied to a freshwater cyanobacterium, Synechococcus sp. (PCC 7942). Analysis of our experimental results provides the following new conclusions: (i) the main chlorophyll (Chl) a emission band at approximately 685 nm that originates in Photosystem (PS) II exhibits typical fast (OPS) and slow (SMT) FI kinetics with both orange (622 nm) and blue (464 nm) excitation. (ii) Similar kinetics are exhibited for its far-red emission satellite band centered at approximately 745 nm, where the PS II contribution predominates. (iii) A significant OPS-SMT-type kinetics of C-phycocyanin emission at approximately 650 nm are observed with the blue light excitation, but not with orange light excitation where the signal rose only slightly to a maximum. The induction of F650 was not caused by an admixture of the F685 fluorescence and thus our data show light-inducible and dark-reversible changes of phycobilin fluorescence in vivo. We discuss possible interpretations of this new observation.

The thylakoid lumen is an important photosynthetic compartment which is the site of key steps in photosynthetic electron transport. The fluidity of the lumen could be a major constraint on photosynthetic electron transport rates. We used Fluorescence Recovery After Photobleaching in cells of the cryptophyte alga Rhodomonas salina to probe the diffusion of phycoerythrin in the lumen and chlorophyll complexes in the thylakoid membrane. In neither case was there any detectable diffusion over a timescale of several minutes. This indicates very restricted phycoerythrin mobility. This may be a general feature of protein diffusion in the thylakoid lumen.

Light-induced deepoxidation of violaxanthin to antheraxanthin and zeaxanthin in plants is associated with the induction of pronounced xanthophyll-dependent non-photochemical quenching (NPQ). To date, a misbalance between a high amount of zeaxanthin in thylakoid membranes and low NPQ has been explained by an absence of lumen acidification (e.g. when NPQ is measured in the dark after high light stress). In this study, we report that this misbalance can also be observed under moderate light. We found this result (deepoxidation state, DEPS, above 55% and NPQ approximately 0.9) in barley leaves treated with 10 microM methyl viologen (MV) under white light (100 micromol photonsm(-2)s(-1), photosynthetically active radiation (PAR), growth irradiance). The addition of MV at this moderate light did not accelerate electron transport in thylakoid membranes, and induced only slight oxidative stress (no lipid peroxidation, almost unchanged maximum yield of photosystem II photochemistry, a decrease in activity of ascorbate peroxidase, and an increase in that of glutathion reductase). We suggest that, in leaves treated under the conditions used here, the lumen acidification induced by light-limited electron transport in thylakoid membranes was high enough to activate violaxanthin deepoxidase, but not sufficiently high to form the expected number of zeaxanthin-dependent quenching centers in photosystem II antennae.

Heat stress causes inhibition of photosynthetic CO(2) assimilation, affects light photosynthetic reactions and accelerates alternative pathways of plastoquinone pool reduction (APPR). We have studied all these heat-sensitive processes after preheating to a broad range of physiological temperatures (24-46 degrees C) to explore a role of these alternative pathways during heat stress. Primarily, the effective quantum yield of PSII photochemistry was reduced (at 40 degrees C). This PSII downregulation was accompanied by the stimulation of APPR and preceded reduction of photosynthetic CO(2) assimilation by 2 degrees ; it occurred after preheating at 42 degrees C because of inhibition in Rubisco (ribulose 1,5-bisphosphate carboxylase/oxygenase) activation process. Thus, we suggest that the heat-induced stimulation of APPR is not associated with the heat-induced inhibition of Calvin cycle as it was reported for other types of stresses. A possible role of APPR in the compensation of PSII downregulation is briefly discussed.

Various osteogenic tumours and bone producing tumour-like lesions of bone were examined for S-100 protein using the immunostaining methods. The positive reaction for S-100 protein of some bone cells was detected not only in osteoblastic osteosarcomas and osteoblastomas, but also in osteoplastic reactive lesions, fibrous dysplasia, Paget's disease and in the tissue of the bony callus. The positive reaction for osteocalcin in these cells showed, that they may be of osteoblastic and osteocytic lineage. The S-100 protein positive bone cells have to be differentiated from chondrocytes persisting in new-formed bone trabecullae. On the one hand S-100 protein positive osteocytes and osteoblasts may represent transient form of osteocytes histogenetically related to chondrocytes, but we were not able to prove such suggestion. Therefore, S-100 protein positivity can be caused by polyclonal character of the used antibody, that is a mixture of three antibodies, S-100 A1, A6 and anti B2. The specificity of these three components differs depending on the histogenesis of cells and their functional status. Such explanation is supported by the results of our study, because we also observed intense positivity of bone cells in the reaction with monoclonal antibody against S-100A6. In contrast, no staining of bone cells was detected with monoclonal antibodies against S-100 A1 and B2.

The aim of our study was to evaluate the occurrence of chondrocytes containing alpha-smooth muscle actin in human normal and diseased cartilage. Immunohistochemistry using monoclonal antibodies for alpha-smooth actin, muscle-specific actin, S-100 protein, CD 34, and desmin was performed on samples of human articular cartilage obtained at autopsy following sudden death, during total hip and knee replacement for osteoarthritis, or after femoral neck fracture in patients without symptoms of osteoarthritis. Moreover, the layers of residual cartilage from chondral posttraumatic defects obtained during preoperative arthroscopy and of newly formed cartilage after autologous-chondrocyte transplantation (Hyalograft C) obtained during second-look arthroscopy were also examined by immunohistochemistry and RT PCR. Our study showed that a significant percentage of articular chondrocytes express alpha-smooth muscle actin in healthy, diseased, and regenerated articular cartilage. Alpha-actin positive chondrocytes (18%) were observed predominantly in the upper zone of normal articular cartilage. By contrast, only approximately 10% of cartilage cells in the deep region stained for this contractile actin isoform. Actin-positive chondrocytes (myochondrocytes) are formed predominantly in response to injury to the osteoarthrotic cartilage, at sites of defective healing, and in newly formed cartilage after autologous chondrocyte transplantation. Fibrocartilage is present in some of these conditions, and it is known that this tissue contains chondrocytes with actin. The presence of myochondrocytes in the surface layer of normal articular cartilage indicates that this region probably plays an important role in maintaining cartilage integrity. Myochondrocytes may utilize the contractile actin isoform in manipulating the extracellular matrix of articular cartilage. It is also possible that actin-containing chondrocytes have a higher potential for regeneration in contrast to chondrocytes that do not contain this contractile material in their cytoplasm.

The objective of this study was to determine whether human auricular chondrocytes can also express alpha-- -smooth muscle actin. Immunohistochemistry using monoclonal antibodies for alpha-smooth actin, muscle-specific actin, beta-actin, S-100 protein, CD34, and desmin was performed on samples of human ear cartilage obtained from 20 individuals during a partial resection of the ear for different reasons. Moreover, the RT-PCR analysis of actin isoforms in auricular chondrocytes was performed. Approximately 60 % of the chondrocytes of the ear cartilage expressed alpha-smooth muscle actin as demonstrated by immunohistochemistry in all the examined samples. Actin-positive chondrocytes occurred in both external subperichondrial layers of the auricular cartilage. This finding was confirmed by the RT-PCR technique. The knowledge of this fact could help us to better understand the chondrocyte changes occurring during the healing and transplantation of auricular cartilage. The question of whether it is necessary to refer to these predominating cells in ear cartilage as myochondrocytes is considered. This is the first report of an unusual immunophenotype and contractile potential for human auricular chondrocytes.