Clarifying main nutritional aspects and resting energy expenditure in children with Smith-Magenis syndrome.

Our study aims to define resting energy expenditure (REE) and describe the main nutritional patterns in a single-center cohort of children with Smith-Magenis syndrome (SMS). REE was calculated using indirect calorimetry. Patients' metabolic status was assessed by comparing measured REE (mREE) with predictive REE (pREE). Patients also underwent multidisciplinary evaluation, anthropometric measurements and an assessment of average energy intake, using a 3-day food diary, which was reviewed by a specialized dietitian. Twenty-four patients (13 M) were included, the median age was 9 years (IC 95%, 6-14 years), 84% had 17p11.2 deletion, and 16% had RAI1 variants. REE was not reduced in SMS pediatric patients, and the mREE did not differ from the pREE. In patients with RAI1 variants (16%, n = 3/24), obesity was more prevalent than those with 17p11.2 deletion (100% vs 38%). Lower proteins intake and higher total energy intake were reported in obese and overweight patients, compared to healthy weight children. No significant difference was found between males and females in energy or macronutrient intake. CONCLUSIONS: In SMS, the onset of obesity is not explained by REE abnormalities, but dietary factors seem to be crucial. Greater concern should be addressed to patients with RAI1 variants. A better understanding of the molecular mechanisms causing obesity in SMS patients could set the basis for possible future targeted therapies. WHAT IS KNOWN: • More than 90% of SMS patients after the age of 10 are overweight or obese. WHAT IS NEW: • Onset of overweight and obesity in SMS pediatric patients is not explained by abnormal resting energy expenditure. • The development of syndrome-specific dietary guidelines for SMS patients should be of utmost relevance and are highly needed.

Predicting the clinical trajectory of feeding and swallowing abilities in CHARGE syndrome.

To date, the feeding and oral-motor abilities of patients with CHARGE syndrome (CS) have not been longitudinally assessed. This study aims to investigate the level of these abilities at different ages and evaluate how they evolve during growth. We retrospectively analysed oral-motor features of 16 patients with molecularly confirmed CS (age range 4-21 years old; mean 11 years; SD 6 years; median 10 years). Nearly 100% of CS new-borns had weak sucking at birth, and half of them demonstrated poor coordination between breathing and swallowing. Over time, the percentages of children with tube feeding dependence (60% at birth) faced a slow but steady decrease (from 33% at 6 months, 25% at 12 months, to 13% at school age) in tandem with the decreasing risk of aspiration. The ability of eating foods requiring chewing was achieved at school age, after the acquisition of an adequate oral sensory processing. A mature chewing pattern with a variety of food textures was not achieved by more than half of patients, including those requiring artificial enteral nutrition. Most patients started prolonged oral-motor treatments with speech language therapists in early childhood. CONCLUSIONS: Although feeding and swallowing disorders are constant features in CS patients, a slow and gradual development of feeding abilities occurs in most cases. Rehabilitation plays a key role in overcoming structural and functional difficulties and attaining appropriate eating skills. WHAT IS KNOWN: • Feeding problems and swallowing dysfunction have been noted in CHARGE syndrome. • The involvement of multiple factors, including structural problems in the mouth, throat, or esophagus, and neurological impairment, make feeding a complicated task in CHARGE individuals. WHAT IS NEW: • Dysphagia gradually improves in most CHARGE children over time, though with a wide interindividual variability. • The percentages of children with tube feeding dependence decrease over time from 60% at birth to 33% at 6 months and 13% at school age.

Drooling outcome measures in paediatric disability: a systematic review.

Drooling, or sialorrhea, is a common condition in patients with cerebral palsy, rare diseases, and neurodevelopmental disorders. The goal of this review was to identify the different properties of sialorrhea outcome measures in children. Four databases were analysed in search of sialorrhea measurement tools, and the review was performed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement. The COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist was used for quality appraisal of the outcome measures. The initial search yielded 891 articles, 430 of which were duplicates. Thus, 461 full-text articles were evaluated. Among these, 21 met the inclusion criteria, reporting 19 different outcome measures that encompassed both quantitative measures and parent/proxy questionnaires.   Conclusions: Among the outcome measures found through this review, the 5-min Drooling Quotient can objectively discriminate sialorrhea frequency in patients with developmental disabilities. The Drooling Impact Scale can be used to evaluate changes after treatment. The modified drooling questionnaire can measure sialorrhea severity and its social acceptability. To date, the tests proposed in this review are the only tools displaying adequate measurement properties. The acquisition of new data about reliability, validity, and responsiveness of these tests will confirm our findings. What is Known: • Although sialorrhea is a recognized problem in children with disabilities, especially those with cerebral palsy (CP), there is a lack of confidence among physicians in measuring sialorrhea. What is New: • Few sialorrhea measures are available for clinicians that may guide decision-making and at the same time have strong evidence to provide confidence in the results. • A combination of both quantitative measures and parent/proxy questionnaires might provide an adequate measurement of sialorrhea in children.

Mortality in septic patients treated with vitamin C: a systematic meta-analysis.

BACKGROUND: Supplementation of vitamin C in septic patients remains controversial despite eight large clinical trials published only in 2020. We aimed to evaluate the evidence on potential effects of vitamin C treatment on mortality in adult septic patients. METHODS: Data search included PubMed, Web of Science, and the Cochrane Library. A meta-analysis of eligible peer-reviewed studies was performed in accordance with the PRISMA statement. Only studies with valid classifications of sepsis and intravenous vitamin C treatment (alone or combined with hydrocortisone/thiamine) were included. RESULTS: A total of 17 studies including 3133 patients fulfilled the predefined criteria and were analyzed. Pooled analysis indicated no mortality reduction in patients treated with vitamin C when compared to reference (risk difference - 0.05 [95% CI - 0.11 to - 0.01]; p = 0.08; p for Cochran Q = 0.002; I2 = 56%). Notably, subgroup analyses revealed an improved survival, if vitamin C treatment was applied for 3-4 days (risk difference, - 0.10 [95% CI - 0.19 to - 0.02]; p = 0.02) when compared to patients treated for 1-2 or > 5 days. Also, timing of the pooled mortality assessment indicated a reduction concerning short-term mortality (< 30 days; risk difference, - 0.08 [95% CI - 0.15 to - 0.01]; p = 0.02; p for Cochran Q = 0.02; I2 = 63%). Presence of statistical heterogeneity was noted with no sign of significant publication bias. CONCLUSION: Although vitamin C administration did not reduce pooled mortality, patients may profit if vitamin C is administered over 3 to 4 days. Consequently, further research is needed to identify patient subgroups that might benefit from intravenous supplementation of vitamin C.

Screening program for latent tuberculosis infection in asylum seekers - a single center experience in Pavia, Italy.

BACKGROUND: The management of Latent Tuberculosis Infection is crucial in fighting Tuberculosis worldwide, and particularly in low incidence European Countries. While guidelines for the management of Tuberculosis in newly arrived immigrants have been issued by the European Center for Disease Control and Prevention and by the National Health Authorities in Italy, these are not widely implemented yet at local level. STUDY DESIGN: We report our program for the screening of Latent Tuberculosis Infection and active Tuberculosis in asylum seekers, jointly implemented by Public Health Authorities and the Infectious Diseases Department of a tertiary care, teaching hospital in Northern Italy. METHODS: We reviewed records of the asylum seekers who were screened at our center via Tuberculin Skin Test and/or Interferon Gamma Release Assay plus chest X-ray and either treated with Isoniazid Preventive Treatment or for active Tuberculosis Disease in case of positive results. RESULTS: We screened 726 migrants, mostly males (97.3%) and from Sub-Saharan Africa (82.2%) and found a high adherence rate for both screening (98.2%) and Isoniazid Preventive Treatment (90.1%). In addition, we found seven cases of active Tuberculosis. CONCLUSIONS: Latent Tuberculosis Infection screening and treatment proved feasible in our program, which should be systematically implemented in asylum seekers reaching Europe.

Evolution and current state of global research on paediatric resuscitation: a systematic scientometric analysis.

BACKGROUND: Paediatric resuscitation is rare but potentially associated with maximal lifetime reduction. Notably, several nations experience high infant mortality rates even today. To improve clinical outcomes and promote research, detailed analyses on evolution and current state of research on paediatric resuscitation are necessary. METHODS: Research on paediatric resuscitation published in-between 1900 and 2019 were searched using Web of Science. Metadata were extracted and analyzed based on the science performance evaluation (SciPE) protocol. Research performance was evaluated regarding quality and quantity over time, including comparisons to adult resuscitation. National research performance was related to population, financial capacities, infant mortality rate, collaborations, and authors' gender. RESULTS: Similar to adult resuscitation, research performance on paediatric resuscitation grew exponentially with most original articles being published during the last decade (1106/1896). The absolute number, however, is only 14% compared to adults. The United States dominate global research by contributing the highest number of articles (777), Hirsch-Index (70), and citations (18,863). The most productive collaboration was between the United States and Canada (52). When considering nation's population and gross domestic product (GDP) rate, Norway is leading regarding population per article (62,467), per Hirsch-Index (223,841), per citation (2226), and per GDP (2.3E-04). Regarding publications per infant mortality rate, efforts of India and Brazil are remarkable. Out of the 100 most frequently publishing researchers, 25% were female. CONCLUSION: Research efforts on paediatric resuscitation have increased but remain underrepresented. Specifically, nations with high infant mortality rates should be integrated by collaborations. Additional efforts are required to overcome gender disparities.

Two case reports of fetal alcohol syndrome: broadening into the spectrum of cardiac disease to personalize and to improve clinical assessment.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) refers to a broad spectrum of disabilities, in infants and children, resulting from moderate to excessive prenatal alcohol exposure. Significant associations with alcohol exposure were already reported with congenital structural heart defects: i.e. ventricular septal defects, atrial septal defects, conotruncal defects. CASES PRESENTATION: We describe two cases of children with FASD, both admitted to the Center for Rare Diseases and Birth Defects of Policlinico Universitario Agostino Gemelli, in whom asymptomatic cardiac rhythm alterations were detected in absence of structural cardiovascular system anomalies or cardiac channelopathies. CONCLUSIONS: No other reports about cardiac rhythm anomalies in individuals affected by FASD are actually available from the literature. We would like to make an alert for clinician, given the possibility of finding anomalies of heart conduction and rhythm in children affected by FASD even without structural congenital heart disease.

Gender Disparities in Authorships of Alzheimer's Disease and Dementia Research Articles.

BACKGROUND: Alzheimer's disease and dementia are an increasing burden affecting more than 50 million patients worldwide. Hence, research has increased significantly in recent decades. It is recognized that female authors are systematically underrepresented in research in general. OBJECTIVE: In this article, we examine gender disparities in academic research on dementia and Alzheimer's disease in the last decade. METHODS: 104,858 male and female authorships from 37,961 original research articles were analyzed. The global and country-specific distribution of women across first, co, and last authorships was determined with the inclusion of a citation and productivity analysis. RESULTS: 42.1% of all authorships and 50.2% of the first, 42.2% of the co, and 32.8% of the last authorships were held by women. Women were less commonly cited, published fewer articles and were also less likely to secure prestigious authorships in articles with multiple authors compared with men. Distinct differences were observed among the countries. CONCLUSION: Substantial growth in the number of prestigious female authorships has been observed to date and is predicted to continue in the future, with an emphasis on the progressive representation of women and a diminishing gender gap.

Reproductive biology of Aechmea bracteata (Sw.) Griseb. (Bromelioideae: Bromeliaceae).

Individuals of Aechmea bracteata show inflorescences with red scape bracts and odourless, yellow, tubular diurnal flowers, with closely arranged sexual organs, producing a large amount of fruits. In order to investigate the reproductive system of this species, a suite of characters was assessed: phenology, floral morphology and biology, nectar production dynamics, and fruit and seed production and germination, as a result of controlled pollination crosses. The study was conducted during two flowering seasons in wild populations in Yucatán, Mexico. Results suggest an annual flowering pattern with one flowering peak; flowers were diurnal, showing partial dichogamy (protandry)-herkogamy, anthers and stigma become mature before floral aperture, which could lead to self-pollination, nectar is produced during anthesis, varying in volume and total sugar concentration during the day; fruits and seeds were produced in all experimental crosses (cross-pollination, obligated cross-pollination, assisted and unassisted selfing, geitonogamy and apomixis), as well as high percentage seed germination. Several species of Aechmea are reportedly self-compatible and autogamous, as suggested by results of selfing and non-assisted selfing crosses, but these results are negated by the presence of apomixis, indicating that the species is apomictic. This is the first report of this breeding system for subgenus Aechmea and the sixth for Bromeliaceae. Polyembryony is here suggested for the first time in this genus and family based on the fact that more seeds were recorded that expected based on ovule numbers. Finally, when performing experimental crosses, estimating reproductive success based on number of seeds is a better approach than number of fruits, due to the effect of pseudogamy.

Transcriptomic analysis of nickel exposure in Sphingobium sp. ba1 cells using RNA-seq.

Nickel acts as cofactor for a number of enzymes of many bacteria species. Its homeostasis is ensured by proteins working as ion efflux or accumulation systems. These mechanisms are also generally adopted to counteract life-threatening high extra-cellular Ni2+ concentrations. Little is known regarding nickel tolerance in the genus Sphingobium. We studied the response of the novel Sphingobium sp. ba1 strain, able to adapt to high Ni2+ concentrations. Differential gene expression in cells cultured in 10 mM Ni2+, investigated by RNA-seq analysis, identified 118 differentially expressed genes. Among the 90 up-regulated genes, a cluster including genes coding for nickel and other metal ion efflux systems (similar to either cnrCBA, nccCBA or cznABC) and for a NreB-like permease was found. Comparative analyses among thirty genomes of Sphingobium species show that this cluster is conserved only in two cases, while in the other genomes it is partially present or even absent. The differential expression of genes encoding proteins which could also work as Ni2+-accumulators (HupE/UreJ-like protein, NreA and components of TonB-associated transport and copper-homeostasis systems) was also detected. The identification of Sphingobium sp. ba1 strain adaptive mechanisms to nickel ions, can foster its possible use for biodegradation of poly-aromatic compounds in metal-rich environments.

Characterization of maize chitinase-A, a tough allergenic molecule.

Food allergies are recognized as an increasing health concern. Proteins commonly identified as food allergens tend to have one of about 30 different biochemical activities. This leads to the assumption that food allergens must have specific structural features which causes their allergenicity. But these structural features are not completely understood. Uncovering the structural basis of allergenicity would allow improved diagnosis and therapy of allergies and would provide insights for safer food production. The availability of recombinant food allergens can accelerate their structural analysis and benefit specific studies in allergology. Plant chitinases are an example of food allergenic proteins for which structural analysis of allergenicity has only partially been reported. The recombinant maize chitinase, rChiA, was purified from Pichia pastoris extracellular medium by differential precipitation and cation exchange chromatography. Enzyme activity was evaluated by halo-assays and microcalorimetric procedures. rChiA modeling was performed by a two-step procedure, using the Swiss-Model server and Modeller software. Allergenicity of rChiA was verified by immunoblot assays with sera from allergic subjects. rChiA is active in the hydrolysis of glycol chitin and tetra-N-acetylchitotetraose and maintains its activity at high temperatures (70°C) and low pH (pH 3). The molecule is also reactive with IgE from sera of maize-allergic subjects. rChiA is a valuable molecule for further studies on structure-allergenicity relationships and as a tool for diagnosing allergies.

Dystonia in Costello syndrome.

BACKGROUND: Costello Syndrome is a rare multiple congenital anomaly disorder caused by de novo heterozygous mutations in the v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS) gene. Recent studies seem to support apparent autosomal dominant inheritance and somatic mosaicism and an association with advanced parental age. Abnormal hand posture has been reported as a typical feature of Costello Syndrome but the pathophysiology of this is unclear. METHODS: We evaluated and described posture and movement in six consecutive subjects with genetically proven Costello Syndrome, in order to better characterize the phenomenology of the associated postural abnormalities and any related motor abnormalities. We also evaluated motor cortex plasticity by applying Paired Associative Stimulation. RESULTS: All the patients presented the typical postural abnormalities reported in Costello Syndrome, in particular the ulnar deviation of fingers. The latter was reducible and not fixed. In addition, patients exhibited more explicit dystonic features of the face, limbs and trunk and altered sensorimotor plasticity consistent with generalized dystonia. CONCLUSIONS: These findings suggest that dystonia may underlie the abnormal postures described in Costello Syndrome patients.

Enhanced human brain associative plasticity in Costello syndrome.

Costello syndrome (CS) is a rare multiple congenital anomaly disorder which is caused by germline mutations in the v-Ha-ras Harvey rat sarcoma viral oncogene homologue (HRAS) proto-oncogene. Experimental data suggest perturbing effects of the mutated protein on the functional and structural organization of networks of cerebral cortex and on the activity-dependent strengthening of synaptic transmission known as long term potentiation (LTP). In five patients with molecularly proven diagnosis of CS and in a group of 13 age-matched control subjects we investigated activity-dependent synaptic plasticity. To this end, we used a paired associative stimulation (PAS) protocol, in which left ulnar nerve stimuli were followed by transcranial magnetic stimulation (TMS) pulses to right cortical hand area, and recorded motor evoked potentials (MEPs) by single pulse TMS from left first dorsal interosseus (FDI) muscle before and after PAS. In 4 out of 5 CS patients and in a subgroup of nine control subjects we also evaluated the time course and the topographical specificity of PAS after-effects. In these two subgroups, MEPs were measured before, immediately after and 30 min after PAS in the left FDI and left abductor pollicis brevis (APB). While the PAS protocol led to a 65% increase of the FDI MEP amplitude in controls, the LTP-like phenomenon was significantly more pronounced in CS patients, with motor responses increased by 230%. In addition, CS patients showed a similar MEP increase in both muscles while control subjects showed a slight increase in APB and only immediately after PAS. We hypothesize that the extremely enhanced PAS after-effects could be due to the influence of HRAS activity on the susceptibility of synapses to undergo LTP.

Wolf-Hirschhorn syndrome with improvement of renal function.

Wolf-Hirschhorn syndrome (WHS) is a chromosomal disorder characterized by partial deletion of the short arm of chromosome 4. We describe a girl with a de novo unbalanced traslocation t(4;7)(p16.2;p22), associated with a mild version of a classical WHS phenotype. She did not present major urinary tract abnormalities but had parenchymal hyperechogenicity at renal ultrasound at the birth with normal renal scintigraphy. She had also a reduction of GFR with elevated levels of blood urea nitrogen and serum potassium until the age of 6 months. We followed the patient with periodic clinical examination and laboratory and radiological investigations and observed at the age of 5 years a normal renal ultrasound without parenchymal hyperechogenicity.

Visual function in Noonan and LEOPARD syndrome.

The aim of the study was to assess various aspects of visual and visuoperceptual function in patients with Noonan syndrome (NS) or LEOPARD syndrome (LS) with mutations affecting the PTPN11, SOS1 and RAF1 genes. Twenty-four patients were assessed with a battery of tests assessing visual function including ophthalmological and orthoptic evaluation and age appropriate behavioural visual tests, including measures of crowding acuity (Cambridge crowding cards), and stereopsis (TNO test). Twenty-one subjects were also assessed with the visuo-motor integration (VMI) test. Twenty of the 24 patients (83%) had abnormalities of visual function on at least one of the tests used to assess visual function or on ophthalmological examination, and 7 of 21 (33%) also had abnormalities on VMI. Ocular movements and stereopsis were most frequently abnormal (50% and 79%, respectively). Our results suggest that visual and visuoperceptual abilities are commonly impaired in patients with Noonan and LEOPARD syndrome and they are probably related to a multifactorial etiology.

Computerized detection of clustered microcalcifications: a modular approach with non-linear filters.

The ideal computerized mammogram processing system still needs to be developed. In order to achieve maximum flexibility we suggest a modular scheme, dividing the processing sequence into functionally autonomous modules. This paper provides a general scheme for detection and/or automated recognition of microcalcifications. Some modules that perform ROI selection are introduced, using special non-linear filters designed for microcalcification detection. A first type of filter selects pixels with specific statistical local features, as compared to the local mean. Among these, only pixels satisfying particular constraints on the local standard deviation are kept. Another type of filter then checks the local mean values of gradient components, so that sharp variations, unrelated to small close objects, can be eliminated. The scheme thus applies different non-linear filters in combination, making precise identification of clustered microcalcifications possible. This modular approach seems greatly to simplify system maintenance and consistency, as well as affording a comparison of different processing techniques and parameters.

Classifying complications of interventional procedures: a survey of practicing radiologists.

PURPOSE: To determine the variability of radiologists' classification of complications from interventional procedures. MATERIALS AND METHODS: Fifteen test cases were selected from a database of morbidity and mortality cases that occurred in our department during the past 2 years. Ten cases were selected randomly, and five were chosen because of classification difficulties within our department. A survey with the case descriptions was presented to 145 SCVIR members via the World Wide Web and 48 were distributed to participants at a statewide angiography club meeting. Participants were asked to complete a short assessment of the their clinical background and to classify each case as "no complication," "minor complication," or "major complication." RESULTS: Thirty-eight percent (74 of 193) of the surveys were completed. Seventy percent (52 of 74) of the respondents were affiliated with an academic program, 12% (nine of 74) were affiliated with private practice groups, and 18% (13 of 74) claimed both academic and private affiliation. The consensus rate in classifying the complications for the randomly selected cases varied from 50% to 95%, with a median of 69%, and the consensus rate in classifying the selected cases varied from 46% to 95%, with a median of 85%. The lowest consensus rates occurred when (i) a significant procedural event was followed by a normal outcome, (ii) when a procedure was aborted, and (iii) when a significant event occurred but did not prolong hospital stay. CONCLUSION: Current criteria for reporting complications are associated with moderate rates of disagreement among interventional radiologists.

Neurite extension occurs in the absence of regulated exocytosis in PC12 subclones.

We have investigated the process leading to differentiation of PC12 cells. This process is known to include extension of neurites and changes in the expression of subsets of proteins involved in cytoskeletal rearrangements or in neurosecretion. To this aim, we have studied a PC12 clone (trk-PC12) stably transfected with the nerve growth factor receptor TrkA. These cells are able to undergo both spontaneous and neurotrophin-induced morphological differentiation. However, both undifferentiated and nerve growth factor-differentiated trk-PC12 cells appear to be completely defective in the expression of proteins of the secretory apparatus, including proteins of synaptic vesicles and large dense-core granules, neurotransmitter transporters, and neurotransmitter-synthesizing enzymes. These results indicate that neurite extension can occur independently of the presence of the neurosecretory machinery, including the proteins that constitute the fusion machine, suggesting the existence of differential activation pathways for the two processes during neuronal differentiation. These findings have been confirmed in independent clones obtained from PC12-27, a previously characterized PC12 variant clone globally incompetent for regulated secretion. In contrast, the integrity of the Rab cycle appears to be necessary for neurite extension, because antisense oligonucleotides against the neurospecific isoform of Rab-guanosine diphosphate-dissociation inhibitor significantly interfere with process formation.