Longitudinal Genotype-Phenotype (Vineland Questionnaire) Characterization of 15 ADNP Syndrome Cases Highlights Mutated Protein Length and Structural Characteristics Correlation with Communicative Abilities Accentuated in Males.

Activity-dependent neuroprotective protein (ADNP) is essential for neurodevelopment and de novo mutations in ADNP cause the ADNP syndrome. From brain pathologies point of view, tauopathy has been demonstrated at a young age, implying stunted development coupled with early/accelerated neurodegeneration. Given potential genotype-phenotype differences and age-dependency, we have assessed here a cohort of 15 individuals (1-27-year-old), using 1-3 longitudinal parent (caretaker) interview/s (Vineland 3 questionnaire) over several years. Our results indicated developmental delays, or even developmental arrests, coupled with potential spurts of development at early ages. Severe outcomes correlated with the truncating high impact mutation, in other words, the remaining mutated protein length as well as with the tested individual age, corroborating the hypothesis of developmental delays coupled with accelerated aging. A significant correlation was noted between mutated protein length and communication, implying a high impact of ADNP on communicative skills. Additionally, correlations were discovered between the two previously described epi-genetic signatures in ADNP emphasizing aberrant acquisition of motor behaviors, with truncating mutations around the nuclear localization signal being mostly affected. Finally, all individuals seem to acquire an age equivalent of 1-6 years, requiring disease modification treatment, such as the ADNP-derived drug candidate, NAP (davunetide), which has recently shown efficacy in women suffering from the neurodegenerative disorder, progressive supranuclear palsy (PSP), a late-onset tauopathy.

Pulmonary functions, nasal symptoms, and quality of life in patients with primary ciliary dyskinesia (PCD).

BACKGROUND: Several factors may influence quality of life (QOL) for patients with primary ciliary dyskinesia (PCD). We aimed to evaluate the association between pulmonary functions, nasal symptoms and QOL in PCD patients. METHODS: A prospective single center study. Patients performed spirometry, whole body plethysmography, forced oscillation technique (FOT), lung clearance index (LCI), 6-min walk test (6MWT), and filled two questionnaires: a specific PCD QOL questionnaire (PCD-QOL) and Sino-nasal outcome test (SNOT-22) questionnaire, assessing symptoms of chronic rhinosinusitis and health related QOL. RESULTS: Twenty-seven patients (56% females), age 19.4 ± 10.5 years were included; their, FEV1 was 74.6 ± 22.7%, and RV/TLC was (157.3 ± 39.3% predicted). Health perception and lower respiratory symptoms domains of PCD-QOL had the lowest score (median [IQR]: 50 [33.3-64.6] and 57.1 [38.9-72.2], respectively). FOT parameters correlated with several PCD-QOL domains. R5 z-score (indicating total airway resistance) and AX z-score (indicating airway reactance) correlated negatively with physical domain (r = -0.598, p = .001, and r = -0.42, p = .03, respectively); R5 z-score also correlated negatively with hearing domain (r = -0.57, p = .002). R5-20 z-score (indicating small airway resistance) correlated negatively with role domain (r = -0.49, p = .03). SNOT-22 score correlated negatively with several PCD-QOL domains (lower respiratory symptoms r = -0.77, p < .001; physical r = -0.72, p < .001; upper respiratory symptoms r = -0.66, p < .001). No correlations were found between spirometry values, LCI, 6MWT, and PCD-QOL. CONCLUSIONS: FOT suggested small airway dysfunction, and correlated negatively with several PCD-QOL domains. Nasal symptoms had strong negative correlations with PCD-QOL. Larger longitudinal studies will further elucidate factors affecting QOL in PCD.

The effect of inspiratory muscle training in PCD and CF patients: A pilot study.

BACKGROUND: Effective work of breathing and bronchial hygiene requires synergy of inspiratory and expiratory muscles. Inspiratory muscle training (IMT) is a part of pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD). There is some evidence of its efficacy in cystic fibrosis (CF) and, recently, in long COVID-19. We are not aware of studies on IMT in primary ciliary dyskinesia (PCD). Our aim was to assess the effect of IMT on respiratory muscle strength and pulmonary function in PCD and CF patients. METHODS: A single center pilot study. Spirometry, lung clearance index (LCI), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) were measured at baseline (visit 1), after a month of IMT with ®POWERbreathe (visit 2), and at follow-up (visit 3). RESULTS: The cohort included 27 patients (19 PCD, 8 CF); mean age 18.4 ± 9.8 years. After a month of IMT, there was a significant increase in MIP and MIP% (6.19-7.44, p = .015; and 81.85%-100.41%, p = .046, respectively), which was sustained at visit 3. Compliance ≥90% led to higher improvement in MIP. In sub-group analysis, improvement in MIP and MIP% remained significant for PCD patients (p = .026 and p = .049, respectively). No significant changes were found in spirometry, MEP or LCI. CONCLUSIONS: IMT was well-tolerated and led to improved inspiratory muscle strength in PCD patients. The clinical implication of improved MIP should be further investigated. Larger, long-term studies are needed to evaluate long-term effects of IMT on pulmonary function, respiratory muscle strength, pulmonary exacerbations, and quality of life.

The effect of nose clip on exercise-induced bronchoconstriction in adolescents.

BACKGROUND: Oral breathing is considered to increase hyper-responsiveness of the airways. Data on the need for nose clip (NC) during exercise challenge test (ECT) in children and adolescents is scarce. Ouraim was to evaluate the role of NC during ECT in children and adolescents. METHODS: A prospective, cohort study; children referred for ECT were evaluated on two separate visits, with and without a NC. Demographic, clinical data and measurements of lung functions were recorded. Allergy and asthma control were evaluated by Total Nasal Symptoms Score (TNSS) and Asthma Control Test (ACT) questionnaires. RESULTS: Sixty children and adolescents (mean age 16.7 ± 1.1 years, 38% Female,) performed ECT with NC and 48 (80%) completed visit 2 (ECT without NC), 8.7 ± 7.9 days after visit 1. Following exercise, 29/48 patients (60.4%) with NC had a decline of ≥12% in forced expiratory volume in the first second (FEV1 ) (positive ECT) compared to only 16/48 (33.3%) positive tests without NC (p = 0.0008). Test result was changed in 14 patients from positive ECT (with NC) to negative ECT (no NC) and in only one patient from negative to positive. The use of NC resulted in greater FEV1 decline (median 16.3% predicted, IQR 6.0-19.1% predicted vs. median 4.5% predicted, IQR 1.6-18.4% predicted, p = 0.0001), and better FEV1 increase after bronchodil at or inhalation compared to ECT without NC. Higher TNSS scores did not predict higher probability to positive ECT. CONCLUSIONS: The use of NC during ECT increases detection rate of exercise induced bronchoconstriction during ECT in the pediatric population. These findings strengthen the recommendation of nasal blockage during ECT in children and adolescents.

Functional capacity and quality of life in patients with vascular ring.

BACKGROUND: Vascular rings are congenital anomalies of the aortic arch that compress the trachea and esophagus and may require corrective surgery. Data about the long-term effects of vascular rings are scarce. We aimed to evaluate the long-term cardiorespiratory, exercise capacity, and quality of life of vascular ring patients. METHODS: A single center prospective study evaluating spirometry, echocardiography, six-minute walk test (6MWT), cardiopulmonary exercise testing (CPET), and quality of life questionnaire (SF36) in patients with a diagnosis of vascular ring, with or without corrective surgery. RESULTS: Twenty-seven patients participated (11.9 ± 6 years, 52% males). The most common diagnosis was double aortic arch (16 patients, 59%). Nineteen patients had corrective surgery (O) and 8 did not (NO). Pulmonary function tests were within normal range in both groups (FEV1 % predicted O = 87.6 ± 16.5, NO = 83 ± 10.8%). However, 11/27 had abnormal FEV1 , 5 had abnormal FVC, and 13 (48%) had flattening of the expiratory curve. 6MWD and oxygen uptake were similarly mildly reduced in both groups; (6MWD O = 80.1 ± 10.7% predicted, NO = 74.1 ± 10.9% and oxygen uptake O = 78.5 ± 23.2% predicted, NO = 73.4 ± 14.3%). Peak O2 pulse (V̇O2 /HR% predicted) was mildly reduced in the NO group (O = 88.4 ± 17.3%, NO = 75.8 ± 16.2%). Echocardiogram and SF36 scores were normal in all patients. CONCLUSIONS: Long-term evaluation of patients born with vascular rings revealed mild pulmonary impairment, reduction in 6MWD, and oxygen uptake. The NO group had also mild reduced peak O2 pulse. Larger, long-term studies assessing functional parameters in operated and non-operated patients are needed to assess disease/surgery limitation in patients with vascular rings. Clinical trial registration number: NCT04781738.

Vineland Adaptive Behavior Scale in a Cohort of Four ADNP Syndrome Patients Implicates Age-Dependent Developmental Delays with Increased Impact of Activities of Daily Living.

Activity-dependent neuroprotective protein (ADNP) is one of the lead genes in autism spectrum disorder/intellectual disability. Heterozygous, de novo ADNP mutations cause the ADNP syndrome. Here, to evaluate natural history of the syndrome, mothers of two ADNP syndrome boys aged 6 and a half and two adults aged 27 years (man and woman) were subjected to Vineland III questionnaire assessing adaptive behavior. The boys were assessed again about 2 years after the first measurements. The skill measures, presented as standard scores (SS) included domains of communication, daily living, socialization, motor skills and a sum of adaptive behavior composite. The age equivalent (AE) and growth scale values (GSV) encompassing 11 subdomains assess the age level at which the subject's raw score is found at a norm sample median and the individual temporal progression, respectively. The norm referenced standard scores age-matched, mean 100 ± 15 of the two children showed the lowest outcome in communication (SS: 20-30). Daily living skills presented SS of 50-60, with a possible potential loss of some activities as the child ages, especially in interpersonal relationships with people outside of the immediate family (boy A). In contrast, in socialization, both children were at the SS of 38, with some positive increase to SS of ~ 45 (interpersonal relations with family members and coping skills, depending on the particular individual), 2 years later. Interestingly, there was an apparent large difference in motor skills (gross and fine) at the young age, with subject B showing a relatively higher level of skills (SS: 70), decreasing to subject A level (SS: 40) 2 years later. Together, the adaptive behavior composite suggested a level of SS: 39-48 with B showing a potential increase (SS: 41-44) and A, a substantial decrease (SS: 48-39), suggesting a strong impact of daily living skills. Adults were at SS: 20, which is the lowest possible score. AE showed minor improvements for subject A and B, with all AE values being below 3 years. GSVs for subject A showed some improvement with age, especially in interpersonal, play and leisure, and gross motor subdomains. GSV for subject B showed minor improvements in the various subdomains. Notably, all subjects showed a percentile rank < 1 compared with age-matched norms except for subject B as to motor domain (2nd percentile) at the age of 6 years. In summary, the results, especially comparing SS and AEs between childhood and adulthood, implied a continuous deterioration of activities compared to the general population, encompassing a slower developmental process coupled to possible neurodegeneration, strongly supporting a great need for disease modifying medicinal procedures.

Immunity waning after COVID vaccine booster vs. infection-better than expected.

BACKGROUND: Rapid decline in antibody-titres after BNT162b2 mRNA COVID-19 vaccine was reported; thus, a booster dose, and recently a second booster were approved. The study aims to discuss immunogenicity throughout the pandemic, especially after booster dose. METHODS: A prospective study conducted in EMMS-Nazareth hospital, Israel. Anti-SARS-CoV-2 IgG antibody titres were monitored every 5 weeks starting from the vaccine's second dose. To detect symptomatic and asymptomatic infections, nasopharyngeal swabs for COVID-19 PCR were obtained bi-weekly, and on suggestive symptoms. Third dose of the vaccine was suggested for all participants 5 months after the second one. A comparison was made between those who received three doses (booster-group), and those who were infected after having two doses (infection-group) or three doses (booster-infection) group. RESULTS: One-hundred participants were included; 66 finished 14 months of follow-up, out of whom 40 received a third dose, 10 received only two doses-all were infected (mean time for infection 5 ± 12.15 weeks before the designated booster), and 12 received three doses and were infected. The mean titres of these three groups 7 months after the designated booster dose (regardless of receiving it) were 1756 ± 2279; 3483 ± 3016 and 6925 ± 3720 BAU/mL, respectively. The booster group had high titres 7 months after the booster dose, comparable to two months after the second dose (p = .69); The booster-infected group had even higher titres. CONCLUSION: Immunogenicity decline rate after the booster dose is slower than the second dose. Timing of second booster in general population is still to be determined; neutralizing-antibody titres might be helpful.

The effect of probiotic administration on metabolomics and glucose metabolism in CF patients.

BACKGROUND AND OBJECTIVES: Cystic fibrosis (CF)-related diabetes (CFRD) affects 50% of CF adults. Gut microbial imbalance (dysbiosis) aggravates their inflammatory response and contributes to insulin resistance (IR). We hypothesized that probiotics may improve glucose tolerance by correcting dysbiosis. METHODS: A single-center prospective pilot study assessing the effect of Vivomixx® probiotic (450 billion/sachet) on clinical status, spirometry, lung clearance index (LCI), and quality of life (QOL) questionnaires; inflammatory parameters (urine and stool metabolomics, blood cytokines); and glucose metabolism (oral glucose tolerance test [OGTT]), continuous glucose monitoring [CGM], and homeostasis model assessment of IR (HOMA-IR) in CF patients. RESULTS: Twenty-three CF patients (six CFRD), mean age 17.7 ± 8.2 years. After 4 months of probiotic administration, urinary cysteine (p = 0.018), lactulose (p = 0.028), arabinose (p = 0.036), mannitol (p = 0.041), and indole 3-lactate (p = 0.046) significantly increased, while 3-methylhistidine (p = 0.046) and N-acetyl glutamine (p = 0.047) decreased. Stool 2-Hydroxyisobutyrate (p = 0.022) and 3-methyl-2-oxovalerate (p = 0.034) decreased. Principal component analysis, based on urine metabolites, found significant partitions between subjects at the end of treatment compared to baseline (p = 0.004). After 2 months of probiotics, the digestive symptoms domain of Cystic Fibrosis Questionnaire-Revised improved (p = 0.007). In the nondiabetic patients, a slight decrease in HOMA-IR, from 2.28 to 1.86, was observed. There was no significant change in spirometry results, LCI, blood cytokines and CGM. CONCLUSIONS: Changes in urine and stool metabolic profiles, following the administration of probiotics, may suggest a positive effect on glucose metabolism in CF. Larger long-term studies are needed to confirm our findings. Understanding the interplay between dysbiosis, inflammation, and glucose metabolism may help preventing CFRD.

Effect of ArtemiC in patients with COVID-19: A Phase II prospective study.

Despite intensive efforts, there is no effective remedy for COVID-19. Moreover, vaccination efficacy declines over time and may be compromised against new SARS-CoV-2 lineages. Therefore, there remains an unmet need for simple, accessible, low-cost and effective pharmacological anti-SARS-CoV-2 agents. ArtemiC is a medical product comprising artemisinin, curcumin, frankincense and vitamin C, all of which possess anti-inflammatory and anti-oxidant properties. The present Phase II placebo-controlled, double-blinded, multi-centred, prospective study evaluated the efficacy and safety of ArtemiC in patients with COVID-19. The study included 50 hospitalized symptomatic COVID-19 patients randomized (2:1) to receive ArtemiC or placebo oral spray, twice daily on Days 1 and 2, beside standard care. A physical examination was performed, and vital signs and blood tests were monitored daily until hospital discharge (or Day 15). A PCR assessment of SARS-CoV-2 carriage was performed at screening and on last visit. ArtemiC improved NEWS2 in 91% of patients and shortened durations of abnormal SpO2 levels, oxygen supplementation and fever. No treatment-related adverse events were reported. These findings suggest that ArtemiC curbed deterioration, possibly by limiting cytokine storm of COVID-19, thus bearing great promise for COVID-19 patients, particularly those with comorbidities.

Insular cortex neurons encode and retrieve specific immune responses.

Increasing evidence indicates that the brain regulates peripheral immunity, yet whether and how the brain represents the state of the immune system remains unclear. Here, we show that the brain's insular cortex (InsCtx) stores immune-related information. Using activity-dependent cell labeling in mice (FosTRAP), we captured neuronal ensembles in the InsCtx that were active under two different inflammatory conditions (dextran sulfate sodium [DSS]-induced colitis and zymosan-induced peritonitis). Chemogenetic reactivation of these neuronal ensembles was sufficient to broadly retrieve the inflammatory state under which these neurons were captured. Thus, we show that the brain can store and retrieve specific immune responses, extending the classical concept of immunological memory to neuronal representations of inflammatory information.

COVID-19 vaccine - Long term immune decline and breakthrough infections.

BACKGROUND: Since the introduction of BNT162b2 mRNA COVID-19 vaccine by Pfizer in late 2020, efficacy and immunogenicity waning of COVID-19 vaccines was reported, and decision making regarding a booster remains a top priority worldwide, a decision that should be made based on breakthrough infection rate and antibody titer decline overtime. METHODS: We conducted a 5-month longitudinal prospective study involving vaccinated healthcare personnel, who were tested monthly for antibody titer, and sampled biweekly and on clinical indication for SARS-COV-2 polymerase chain reaction (PCR), to determine antibody decline and breakthrough infection. RESULTS: 100 participants were recruited to the study. Antibody titer reached the climate after one month of the second dose of the vaccine, and declined rapidly thereafter: the median antibody levels were 895; 22,266; 9,682; 2,554 and 1,401 AU/ml in the day of the second dose, and in one month interval thereafter, respectively. In other words, four months after vaccination, the mean antibody level was 6% of the peak levels. During the study period, 4 breakthrough infections were diagnosed, 2 of which were asymptomatic, and the remaining two were mild cases; sharp elevation of antibody titer was seen after infection. CONCLUSION: Antibody titer drops rapidly one month after the second dose of the vaccine. All infections within the study period were mild or asymptomatic, after which titer elevations were seen.

Optogenetic activation of local colonic sympathetic innervations attenuates colitis by limiting immune cell extravasation.

The sympathetic nervous system is composed of an endocrine arm, regulating blood adrenaline and noradrenaline, and a local arm, a network of fibers innervating immune organs. Here, we investigated the impact of the local arm of the SNS in an inflammatory response in the colon. Intra-rectal insertion of an optogenetic probe in mice engineered to express channelrhodopsin-2 in tyrosine hydroxylase cells activated colonic sympathetic fibers. In contrast to systemic application of noradrenaline, local activation of sympathetic fibers attenuated experimental colitis and reduced immune cell abundance. Gene expression profiling showed decreased endothelial expression of the adhesion molecule MAdCAM-1 upon optogenetic stimulation; this decrease was sensitive to adrenergic blockers and 6-hydroxydopamine. Antibody blockade of MAdCAM-1 abrogated the optogenetic effect on immune cell extravasation into the colon and the pathology. Thus, sympathetic fibers control colonic inflammation by regulating immune cell extravasation from circulation, a mechanism likely relevant in multiple organs.

Factors associated with complicated pneumonia in children.

INTRODUCTION: Community acquired pneumonia (CAP) is a leading cause of morbidity in children, despite advances in health care and anti-pneumococcal vaccine. Complicated pneumonia accounts for a significant burden with prolonged hospitalization. Finding risk factors for complicated pneumonia may help in tailoring management. We aimed to identify risk factors for developing complicated pneumonia and need for intervention. METHODS: A retrospective single tertiary center study. Children admitted with a diagnosis of CAP and/or complicated pneumonia (parapneumonic effusion, empyema, necrotizing pneumonia, and lung abscess) on January 2001-March 2020 were included. Demographic, clinical, and laboratory parameters were collected using MDclone, a data acquisition tool. Risk factors for complicated pneumonia (on admission or during hospitalization) and risk for intervention were analyzed. RESULTS: A total of 6778 children with pneumonia were included; 323 arrived at the Emergency Department with complicated pneumonia while 232 developed a complication during hospitalization. Risk factors for complicated pneumonia (on admission or during hospitalization) were Arab ethnicity, cardiac disease, increased age, and CRP and low O2 Sat (OR = 2.236 p < .001, OR = 4.376 p < .001, OR = 1.131 p < .001, OR = 1.065 p < .001 and OR = 0.959 p = .029, respectively). O2 Sat was lower, while fever and CRP were higher in patients with complicated pneumonia requiring intervention. CONCLUSIONS: Identifying children at risk for complicated pneumonia may help in decision-making in the Emergency Department and during hospitalization. The increased risk of the Arab population for complicated pneumonia requires further understanding. Addressing the underlying socioeconomic and ethnic health inequities may help to decrease the disease burden in this population.

Understanding the interplay between factors that influence bone mineral density in CF.

BACKGROUND AND OBJECTIVES: Multiple factors affect bone mineral density (BMD) in cystic fibrosis (CF). Our aim was to perform comprehensive analyses of parameters potentially contributing to BMD. METHODS: A prospective single-center study assessing BMD, and correlations with multiple parameters including pancreatic status, lung functions, 6-minute walk test (6MWT), clinical score (modified Shwachman-Kulczycki [SK] score), vitamin D, nutritional intake, hand grip strength (HGS), habitual physical activity (smart watches), and quality of life (SF-36 questionnaire). RESULTS: Forty CF patients, mean age 18.3 ± 8.1 years, forced expiratory volume in 1 second 74.7% ± 17.9% predicted. Fifteen (37.5%) and 11 (27.5%) had osteopenia and osteoporosis, respectively. BMD was similar in pancreatic sufficient (pancreatic sufficient [PS], n = 15) and insufficient (pancreatic insufficient [PI], n = 25); median hip z score -1.5 ((-2.7)-(+0.2)) vs -1.5 ((-3.5)-(+0.7)), P = .79; spine -0.8 ((-2.2)-(+2)) vs -1.2 ((-4.4)-(+1.5)), P = .39 in PS vs PI, respectively. BMD correlated with HGS (r = .72, P < .001 hip; r = .52, P = .001 spine) and fat-free mass index (r = .81, P < .001 hip; r = .63, P < .001 spine). BMD z score correlated weakly with SK score and moderately with SF-36 general health. Data from smart watches, nutrition questionnaires, and 6MWT did not correlate with BMD. In a multivariate model, age and SK score predicted spine z score BMD. CONCLUSIONS: A substantial number of CF patients have low BMD. Similar rates in PS and PI suggest that other factors, such as disease severity, may contribute to low BMD. SK and age, which can easily be obtained even with limited resources, were the best predictors of low BMD. Further larger multicenter studies are warranted to evaluate the contribution of multifactorial etiologies to low BMD in CF.

Short-term sleep deprivation in mice induces B cell migration to the brain compartment.

Increasing evidence highlight the involvement of immune cells in brain activity and its dysfunction. The brain's immune compartment is a dynamic ensemble of cells that can fluctuate even in naive animals. However, the dynamics and factors that can affect the composition of immune cells in the naive brain are largely unknown. Here, we examined whether acute sleep deprivation can affect the brain's immune compartment (parenchyma, meninges, and choroid plexus). Using high-dimensional mass cytometry analysis, we broadly characterized the effects of short-term sleep deprivation on the immune composition in the mouse brain. We found that after 6 h of sleep deprivation, there was a significant increase in the abundance of B cells in the brain compartment. This effect can be accounted for, at least in part, by the elevated expression of the migration-related receptor, CXCR5, on B cells and its ligand, cxcl13, in the meninges following sleep deprivation. Thus, our study reveals that short-term sleep deprivation affects the brain's immune compartment, offering a new insight into how sleep disorders can affect brain function and potentially contribute to neurodegeneration and neuroinflammation.

The Effect of a 30-Min Water-Pipe Smoking Session on Cognitive Measures and Cardio-Pulmonary Parameters.

INTRODUCTION: One session of water-pipe tobacco smoking (WPS) can increase carboxyhemoglobin (COHb) to levels comparable to those reported in carbon monoxide poisoning, which may cause memory impairment and confusion. METHODS: A prospective study evaluating healthy volunteers pre- and post-30 min of WPS session. Primary outcome parameters were executive cognitive measures [digit span test and Paced Auditory Serial Addition Test (PASAT)]. The effect of repeated cognitive testing 30 min apart without WPS was evaluated in age- and sex-matched healthy volunteers. Secondary outcome parameters included cardio-pulmonary, COHb, serum nicotine, and cytokine changes. RESULTS: Thirty-five subjects aged 25.6 ± 4.5 years smoked water-pipe for a 30-min session. Control group included 20 subjects aged 25.2 ± 5.1 years. Digit span test median score decreased after WPS (16 and 15, respectively, p = .003), insignificant decrease in controls. Median PASAT score increased after WPS (49 and 52, respectively, p = .009); however, a much larger significant increase was observed in controls (p ≤ .001). One WPS session resulted in significant increases in heart and respiratory rates and significant decrease in FEF25-75%. Post WPS, median COHb levels increased (from 2.2% to 10.7%, p < .0001) as did median serum nicotine levels (from 1.2 to 26.8 ng/mL, p < .0001). Serum cytokines levels: IL-2 and IL-6 increased (p < .0001 for each), and IL-10 and IL-5 decreased (p < .0001 and p = .04, respectively). CONCLUSIONS: One session of WPS resulted in significant negative effects on cognitive executive measures, significant increases in COHb and serum nicotine levels, and significant changes in serum cytokines. Our findings call for increasing awareness towards the possible consequences of cognitive alterations following a 30-min session of WPS. IMPLICATIONS: One 30-min session of water-pipe smoking resulted in negative effects on executive cognitive measures, increased carboxyhemoglobin and serum nicotine, and significant changes in serum cytokine levels. This study adds to the accumulating evidence on the harmful effects of water-pipe smoking, a growing epidemic, and calls for awareness of its possible consequences of acute cognitive alterations.

Factors predicting length of stay in bronchiolitis.

INTRODUCTION: Despite advances in medical knowledge, the treatment of viral bronchiolitis is mainly supportive. Antiviral therapies are being investigated in clinical trials. Identifying population-attributable risk factors for RSV hospitalization may help prioritizing targeted treatment. AIM: To utilize MDClone, a data acquisition tool, to examine factors associated with the risk of hospitalization and length of stay (LOS) in bronchiolitis. METHODS: A single tertiary medical center retrospective study. Infants discharged with a diagnosis of bronchiolitis between January 2001 and March 2019 were included. Demographic, clinical, laboratory, microbiologic parameters and co-morbidities were collected. Correlations with the risk of hospitalization and LOS were examined. RESULTS: A total of 4793 infants with bronchiolitis, 3851 (80.3%) previously healthy, were seen; 975 visited emergency room only; 3311 were hospitalized in pediatric wards and 507 required pediatric intensive care unit. O2 saturation, age and fever correlated with the risk of hospitalization (OR = 0.703, p < 0.0001, OR = 0.4, p = 0.024 and OR = 2.388, p < 0.0001, respectively). Saturation, fever, gestational age and birth weight correlated with LOS (r = -0.283, p = 0.000; r = 0.16, p = 0.000; r = -0.12, p = 0.00; and r = -0.117, p = 0.00, respectively). Rates of hospitalization were higher (81.1% vs. 75.6%, p = 0.0008) and LOS was longer (median 2.97 vs. 2.73 days, p < 0.001) in Arabs than in Jews. In a multivariate model, saturation, fever, gestational age and age predicted LOS. Saturation and ethnicity predicted LOS for previously healthy infants. Prematurity and cardiac anomalies increased LOS (p = 0.016 and p < 0.0001, respectively). CONCLUSIONS: Population-based data may enable predicting disease severity and LOS in bronchiolitis. Focusing on children at greatest risk may aid targeting new therapies.

Exercise capacity in patients with cystic fibrosis vs. non-cystic fibrosis bronchiectasis.

BACKGROUND: Bronchiectasis is associated with morbidity, low exercise capacity and poor quality of life. There is a paucity of data on exercise capacity using cardiopulmonary exercise test (CPET) in non-cystic fibrosis (CF) bronchiectasis. Our aim was to compare exercise capacity using CPET in CF and non-CF bronchiectasis patients. METHODS: Cross-sectional retrospective/prospective controlled study assessing CPET using cycle ergometer. Exercise parameters and computed tomography (CT) findings were compared. Results: Hundred two patients with bronchiectasis and 88 controls were evaluated; 49 CF (age 19.7 ± 9.7 y/o, FEV1%predicted 70.9 ± 20.5%) and 53 non-CF (18.6 ± 10.6 y/o, FEV1%predicted 68.7 ± 21.5%). Peak oxygen uptake (peak [Formula: see text]) was similar and relatively preserved in both groups (CF 1915.5±702.0; non-CF 1740±568; control 2111.0±748.3 mL/min). Breathing limitation was found in the two groups vs. control; low breathing reserve (49% in CF; 43% non-CF; 5% control) and increased [Formula: see text] (CF 31.4±4.1, non-CF 31.7±4.1 and control 27.2 ± 2.8). Oxygen pulse was lower in the non-CF; whereas a linear relationship between peak [Formula: see text] vs. FEV1 and vs. FVC was found only for CF. CT score correlated with [Formula: see text] and negatively correlated with [Formula: see text] and post exercise oxygen saturation (SpO2). CONCLUSIONS: CPET parameters may differ between CF and non-CF bronchiectasis. However, normal exercise capacity may be found unrelated to the etiology of the bronchiectasis. Anatomical changes in CT are associated with functional finding of increased [Formula: see text] and decreased SpO2. Larger longitudinal studies including cardiac assessment are needed to better study exercise capacity in different etiologies of non-CF bronchiectasis. TRIAL REGISTRATION: ClinicalTrials.gov, registration number: NCT03147651.