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Introduction/aims: Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is caused by RFC1 expansions. Sensory neuronopathy, polyneuropathy, and involvement of motor, autonomic, and cranial nerves have all been described with RFC1 expansions. We aimed to describe the electrodiagnostic features of patients with RFC1 expansions through multimodal electrophysiological investigations., Methods: Thirty-five patients, with a median age of 70 years, and pathologic biallelic repeat expansions in the RFC1 gene, were tested for motor and sensory nerve conduction, flexor carpi radialis (FCR) and soleus H-reflexes, blink reflex, electrochemical skin conductance, sympathetic skin response (SSR), and heart rate variability with deep breathing (HRV)., Results: Only 16 patients (46%) exhibited the full clinical CANVAS spectrum. Distal motor amplitudes were normal in 30 patients and reduced in the legs of five patients. Distal sensory amplitudes were bilaterally reduced in a non-length dependent manner in 30 patients. Conduction velocities were normal. Soleus H-reflexes were abnormal in 19/20 patients of whom seven had preserved Achilles reflexes. FCR H-reflexes were absent or decreased in amplitude in 13/14 patients. Blink reflex was abnormal in 4/19 patients: R1 latencies for two patients and R2 latencies for two others. Fourteen out of 31 patients (45%) had abnormal results in at least one autonomic nervous system test, either for ESC (12/31), SSR (5/14), or HRV (6/19)., Discussion: Less than half of the patients with RFC1 expansions exhibited the full clinical CANVAS spectrum, but nearly all exhibited typical sensory neuronopathy and abnormal H-reflexes. Involvement of small nerve fibers and brainstem neurons was less common., (© 2024 The Author(s). Muscle & Nerve published by Wiley Periodicals LLC.)

Children with Down syndrome (DS) show delayed acquisition of cognitive and functional skills compared to typically developing children. The objective of this study was to accurately describe early development of infants and young children (children hereafter) with DS based on a large recent sample. We carried out repeated measure analysis of the global development quotient (GDQ) and developmental age using data from the Assessment of Systematic Treatment with Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children (ACTHYF) study (NCT01576705). Because there was no statistically significant difference in the primary endpoint between active treatment and placebo, data from all treatment groups were pooled for post-hoc analysis. Data of 141 children with DS aged 6-18 months at inclusion were analyzed. Mean GDQ decreased over the study period, especially in the youngest age classes ([6-9] and [9-12] months), indicating that acquisition of skills occurred at a slower pace compared to typically developing children. Strongest deficits were observed for motor and hearing and language skills. Only GDQ at baseline correlated significantly with evolution of GDQ. Future studies should aim at elucidating the mechanisms underlying motor and language development. Early pharmacological interventions together with early childhood therapies might be necessary to improve the developmental trajectory of children with DS., (© 2021 Wiley Periodicals LLC.)

Down syndrome (DS) is a genetic neurodevelopmental disorder. In individuals with DS, a multidisciplinary approach to care is required to prevent multiple medical complications. The aim of this study was to describe the rehabilitation, medical care, and educational and social support provided to school-aged French DS patients with varying neuropsychological profiles. A mixed study was conducted. Quantitative data were obtained from a French multicentre study that included patients aged 4-20 years with diverse genetic syndromes. Qualitative data were collected by semi-structured face-to-face interviews and focus groups. Ninety-five DS subjects with a mean age of 10.9 years were included. Sixty-six per cent had a moderate intellectual disability (ID) and 18.9% had a severe ID. Medical supervision was generally multidisciplinary but access to medical specialists was often difficult. In terms of education, 94% of children under the age of six were in typical classes. After the age of 15, 75% were in medico-social institutions. Analysis of multidisciplinary rehabilitation conducted in the public and private sectors revealed failure to access physiotherapy, psychomotor therapy and occupational therapy, but not speech therapy. The main barrier encountered by patients was the difficulty accessing appropriate facilities due to a lack of space and long waiting lists. In conclusion, children and adolescents with DS generally received appropriate care. Though the management of children with DS has been improved considerably, access to health facilities remains inadequate., (Copyright © 2021. Published by Elsevier Masson SAS.)

Smith-Magenis syndrome (SMS), characterized by dysmorphic features, neurodevelopmental disorder, and sleep disturbance, is due to an interstitial deletion of chromosome 17p11.2 (90%) or to point mutations in the RAI1 gene. In this retrospective cohort, we studied the clinical, cognitive, and behavioral profile of 47 European patients with SMS caused by a 17p11.2 deletion. We update the clinical and neurobehavioral profile of SMS. Intrauterine growth was normal in most patients. Prenatal anomalies were reported in 15%. 60% of our patients older than 10 years were overweight. Prevalence of heart defects (6.5% tetralogy of Fallot, 6.5% pulmonary stenosis), ophthalmological problems (89%), scoliosis (43%), or deafness (32%) were consistent with previous reports. Epilepsy was uncommon (2%). We identified a high prevalence of obstipation (45%). All patients had learning difficulties and developmental delay, but ID range was wide and 10% of patients had IQ in the normal range. Behavioral problems included temper tantrums and other difficult behaviors (84%) and night-time awakenings (86%). Optimal care of SMS children is multidisciplinary and requires important parental involvement. In our series, half of patients were able to follow adapted schooling, but 70% of parents had to adapt their working time, illustrating the medical, social, educative, and familial impact of having a child with SMS., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Prader-Willi syndrome (PWS) is a rare genetic neurodevelopmental disorder with a characteristic behavioural phenotype. A multidisciplinary approach to care is required to prevent multiple medical complications in individuals affected by PWS. The aim of this study was to describe the rehabilitation, medical care, educational and social support provided to school-aged French PWS patients with varying neuropsychological profiles. Data were obtained from a French multicentre study that included patients aged 4-20 years with diverse genetic syndromes. Nineteen PWS subjects with a mean age of 9.2 years were included. The mean full-scale intellectual quotient (IQ) was 58 (Wechsler scale). There were frequent dissociations between verbal and performance IQ that were not associated with a specific profile. We also observed lower autonomy and communication scores (5.3 years and 5.9 years equivalent, respectively, Vineland scale), the absence of hyperactivity (Conners scale), and the presence of behavioural abnormalities (CBCL scale). Multidisciplinary medical supervision was generally coordinated by the paediatric endocrinologist and did not always include follow-up with all of the recommended specialists, in particular with a paediatric psychiatrist. Analysis of multidisciplinary rehabilitation conducted in public and private-sector establishment revealed failings in psychological support, occupational therapy and dietary follow-up. Regarding education, most children younger than 10 years were in normal schools, while older individuals were often cared for in medico-social institutions. In conclusion, children and adolescents with PWS generally received appropriate care. Though there have been considerable improvements in the management of children with PWS, reference centres should continue reinforcing the coordination of multidisciplinary supervision., (Copyright © 2020. Published by Elsevier Masson SAS.)

Purpose: To determine whether folinic acid (FA) and thyroxine, in combination or alone, benefit psychomotor development in young patients with Down syndrome (DS)., Methods: The Assessment of Systematic Treatment With Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children (ACTHYF) was a single-center, randomized, double-blind, placebo-controlled phase 3 trial in DS infants aged 6-18 months. Patients were randomly assigned to one of four treatments: placebo, folinic acid (FA), L-thyroxine, or FA+L-thyroxine, administered for 12 months. Randomization was done by age and sex. The primary endpoint was adjusted change from baseline in Griffiths Mental Development Scale global development quotient (GDQ) after 12 months., Results: Of 175 patients randomized, 143 completed the study. The modified intention-to-treat (mITT) population included all randomized patients who did not prematurely discontinue due to elevated baseline thyroid stimulating hormone (TSH). Baseline characteristics in the mITT were well balanced between groups, with reliable developmental assessment outcomes. Adjusted mean change in GDQ in the mITT showed similar decreases in all groups (placebo: -5.10 [95% confidence interval (CI) -7.84 to -2.37]; FA: -4.69 [95% CI -7.73 to -1.64]; L-thyroxine: -3.89 [95% CI -6.94 to -0.83]; FA+L-thyroxine: -3.86 [95% CI -6.67 to -1.06]), with no significant difference for any active treatment group versus placebo., Conclusion: This trial does not support the hypotheses that thyroxine and/or folinic acid improve development of young children with DS or are synergistic. This trial is registered with ClinicalTrials.gov number, NCT01576705.

The use of microbial source tracking (MST) marker genes has grown in recent years due to the need to attribute point and non-point fecal contamination to specific sources. Quantitative microbial risk assessment (QMRA) is a modeling approach used to estimate health risks from exposure to feces-contaminated water and associated pathogens. A combination of these approaches [quantitative MST (qMST) and QMRA] can provide additional pathogen-related information for prioritizing and addressing health risks, compared to reliance on conventional fecal indicator bacteria (FIB). To inform expansion of this approach, a review of published qMST-QMRA studies was conducted to summarize the state of the science and to identify research needs. The reviewed studies primarily aimed to identify what levels of MST marker genes in hypothetical recreational waterbodies would exceed the United States Environmental Protection Agency (USEPA) risk benchmarks for primary contact recreators. The QMRA models calculated relationships between MST marker gene(s) and reference pathogens based on published data in the literature. The development of a robust, accurate relationship was identified as an urgent research gap for qMST-QMRA. This metric requires additional knowledge to quantify the relationship between MST marker genes and the degree of variability in decay of pathogens as a dynamic function of environmental conditions and combinations of fecal sources at multiple spatial and temporal scales. Improved characterization of host shedding rates of host-associated microorganisms (i.e., MST marker genes), as well as fate and transport of these microorganisms and their nucleic acids, would facilitate expansion of this approach to other exposure pathways. Incorporation of information regarding the recovery efficiency, and host-specificity of MST marker genes into QMRA model parameters, and the sensitivity analysis, would greatly improve risk management and site-specific water monitoring criteria., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

CrAssphage are recently-discovered DNA bacteriophages that are prevalent and abundant in human feces and sewage. We assessed the performance characteristics of a crAssphage quantitative PCR (qPCR) assay for quantifying sewage impacts in stormwater and surface water in subtropical Tampa, Florida. The mean concentrations of crAssphage in untreated sewage ranged from 9.08 to 9.98 log 10 gene copies/L. Specificity was 0.927 against 83 non-human fecal reference samples and the sensitivity was 1.0. Cross-reactivity was observed in DNA extracted from soiled poultry litter but the concentrations were substantially lower than untreated sewage. The presence of the crAssphage marker was monitored in water samples from storm drain outfalls during dry and wet weather conditions in Tampa, Florida. In dry weather conditions, 41.6% of storm drain outfalls samples were positive for the crAssphage marker and the concentrations ranged from 3.60 to 4.65 log 10 gene copies/L of water. After a significant rain event, 66.6% of stormwater outlet samples were positive for the crAssphage marker and the concentration ranged from 3.62 to 4.91 log 10 gene copies/L of water. The presence of the most commonly used Bacteroides HF183 marker in storm drain outfalls was also tested along with the crAssphage. Thirteen samples (55%) were either positive (i.e., both markers were present) or negative (i.e., both markers were absent) for both the markers. Due to the observed cross-reactivity of this marker with DNA extracted from poultry litter samples, it is recommended that this marker should be used in conjunction with additional markers such as HF183. Our data indicate that the crAssphage marker is highly sensitive to sewage, is adequately specific, and will be a valuable addition to the MST toolbox., (Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.)

Introduction: The diagnostic sensitivity of repetitive nerve stimulation (RNS) in patients with myasthenia gravis (MG) varies as a function of the number of muscles or the choice of muscles studied., Methods: By exploring 12 muscles bilaterally, we evaluated the global sensitivity of RNS at rest, the sensitivity in different clinical forms, and the sensitivity of different combinations of muscles studied., Results: The global sensitivity of RNS was 82%, and specificity was 100%. The sensitivity in the MG subgroups was as follows: ocular (O) = 67%; oculobulbar (OB) = 86%; and generalized (G) = 89%. The most sensitive muscles were the anconeus in group O, orbicularis oculi (OO) or nasalis in group OB, and the trapezius in group G. Maximum sensitivity was obtained by exploring OO, trapezius, and anconeus bilaterally., Conclusions: We recommend bilateral exploration of at least 3 muscles, a facial muscle, trapezius, and anconeus. Muscle Nerve 55: 532-538, 2017., (© 2016 Wiley Periodicals, Inc.)

Background: Currently the uptake of the influenza vaccine amongst Australian hospital staff remains low. While some staff members choose not to receive the vaccine, others may feel decisional conflict around whether to receive the vaccine or not. Having access to information that is personalized to the staff members' concerns may alleviate this conflict. Our study aimed to explore the attitudes of hospital staff towards an online decision aid (DA), which focuses on influenza and the vaccine. We were also interested to examine whether they accepted the new tool and whether they had any suggestions for improvements., Methods: Forty-one semi-structured interviews were undertaken with a range of hospital staff from two major public hospitals in Sydney and Melbourne, Australia in 2013. Emails and posters were used to inform staff members about the study. Thematic analysis was performed to explore the attitudes of hospital staff towards the DA., Results: Our participants were well aware of the time/location of the staff vaccination clinics, however very few reported attending or receiving any educational material about the disease or the vaccine. Amongst those who did receive material, they felt that the messages were "dumbed down". There was a mostly positive response to the DA from participants, however they felt that unless it was included as part of mandatory training or orientation, it would be difficult to get staff to use the tool., Conclusions: Previous studies have established that education is an important component of an influenza vaccination program. We believe that the decision aid offers an alternative approach to delivering balanced information to staff members, which may reduce workload burdens on administrators and drive up rates.

We retrospectively analyzed three patients with pure motor neuronopathy followed for more than four years in our center. The patients presented a rapidly progressive lower motor neuron syndrome (LMNS) over the course of a few weeks leading to a severe functional impairment. The neurological symptoms preceded the diagnosis of a breast adenocarcinoma and a thymoma in the first two patients, one of them with anti-CV2/CRMP5 antibodies. Cancer was not detected in the third patient who had circulating anti-Hu antibodies. A final diagnosis of paraneoplastic syndrome was made after investigations for alternative causes of lower motor neuron syndrome. Early diagnosis, combined treatment of the underlying cancer, and immunomodulatory treatment led to neurological improvement of the disease in two out of the three cases in which the cancer was diagnosed. Cases of subacute LMNS with rapid progression may occur as an expression of a paraneoplastic neurological syndrome. Identification of these syndromes is important, as the treatment of underlying malignancy along with immunomodulatory treatment may result in a favorable long-term outcome of these potentially fatal diseases., (Copyright © 2015 Elsevier B.V. All rights reserved.)

It is crucial to assess patients' understanding of and readiness to participate in infection control programs. While 80% of hospital patients reported that they were willing to help hospital staff with infection prevention, many felt that they would not feel comfortable asking a healthcare worker to sanitize his or her hands.

We report on a 6-year-old child with a de novo 1.6 Mb deletion in the 3q26.31q26.32 region identified by SNP array, involving only one relevant gene: TBL1XR1. The girl shows non-specific, mild to moderate intellectual deficiency but no autistic behavior. Point mutations in TBL1XR1 have recently been implicated in three patients with intellectual disability (ID) and autistic features. Our report supports that haploinsufficiency for TBL1XR1 could be implicated in non-ASD autosomal dominant ID., (© 2014 Wiley Periodicals, Inc.)

Aim: To compare technical feasibility and complications of radiologically arm port device implantation using arm venography exclusively (API-Group B) with chest port placement using cephalic vein cutdown (CVC-Group A), in advanced consecutive head and neck cancer patients (HNP)., Methods: Port device placement was attempted in 225 consecutive HNP. Decision for inclusion in Group A or B was made first by the availability of the surgeon/radiologist to perform the procedure, second by contraindications of each technique. Patient transfer from one group to the other was recorded as well as technical feasibility, complications and device specific duration in this retrospective study., Results: Technical success was statistically higher in Arm Port Group (99.1%) compared to Chest Port Group (75.2%). Device specific duration rate of the whole population was 53% (95%CI) [0.47-0.60] at 6 months, 44.1% (95%CI) [24.4-37.8] at 12 months and 8% (95%CI) [4.4-14.5] at 24 months. Median follow-up was 5.55 months (range: 0.032-9.6] in Group A versus 5.90 months [range: 0.06-27.6] (p=ns) in Group B. Complication rate was 15.9% in Group A versus 8.9% in Group B corresponding to a complication rate per patient-implantation-days of 0.66/1000 patient-days (A) versus 0.42/1000 patient-days (B). Premature port device explantation rate was 4.4% (A) versus 5.4% (B). Axillary and subclavian venous thrombosis was the main complication and occurred in 12 Group A patients and three Group B patients. Venous thrombosis rate was 0.37/1000 patient-days (A) and 0.13/1000 patient-days (B) (p=0.03)., Conclusions: A few data exist about device insertion in HNP in whom venous cervical access is contraindicated. This comparative study demonstrates that both implantation techniques are safe and effective. The higher technical success rate with 0% heavy sedation, the lower venous thrombosis rate in the API group, and the 5.3% (A-B) patient transfer rate argue in favour of arm port placement in HNP. Indications for API include patients with an ipsilateral major pectoralis-myocutaneous flap, with radiodermatitis, tumour recurrence in the neck and upper chest, or with respiratory impairment.

In early 2003 Severe Acute Respiratory Syndrome (SARS) became an international globe-travelling virus; it began this frequent flyer journey from mainland China, and travelled to 30 countries across the world. By the end of its worldwide journey it had killed over 800 people and infected over 8000. As part of Australia's response to contain the virus, screening of all arriving international passengers was introduced throughout all of Australia's international airports. This article is a reflection on the experiences that five infection control practitioners (ICPs) had with implementing and conducting this service at Sydney's Mascot International Airport., (© 2003 Australasian College for Infection Prevention and Control.)

Atypical prostatic leiomyoma is a very rare benign tumor. We report here a new case with a cytodensitometric analysis. The result of cytodensitometry is a polyploid tumor that is well correlated with the morphology of nuclear multilobulated cells of this tumor. The differential diagnosis is essentially the leiomyosarcoma which is characterized by the absence of mitotic activity.

Because NO is not very reactive in an oxygen-free buffer, a significant part of serotonin (5-HT) is transformed by NO in nondeaerated phosphate buffer, at pH 7.4, into (4-serotonyl)-4-serotonin, 4-nitrososerotonin, and 4-nitroserotonin. Dimerization and above all nitrosation occur through the HNO2 reaction in the pH 4-6 range, possibly via radical mechanism involving N2O3. 5-HT is readily a substrate for nitrosation by HNO2 or N2O3, whereas tyrosine was described as not very reactive under the same conditions. Peroxynitrite converts 5-HT to the (4-serotonyl)-4-serotonin and to the 4-nitro derivative. In order to evaluate whether such structural modifications could modulate the biological properties of 5-HT, arterial pressure was measured after i.v. bolus injection of these derivatives to anesthetized rats. Injections of the 4-nitroso- and 4-nitro-5-HT resulted in first a brief hypotensive response and did not give the subsequent hypertensive and hypotensive phases observed with 5-HT. Finally, when tested on some cloned rat 5-HT receptors stably transfected into LMTK- cells, both 4-nitroso and 4-nitro derivatives behaved as agonists and antagonists toward 5-HT1B and 5-HT2B receptors, respectively.

BOP-Cl was found to be an efficient coupling reagent for the introduction of thiopeptide bonds on imino acid residues (Pro, Sar). Boc-amino monothioacids were coupled at moderate temperature (0 degree C-RT) with fair yields and with retained optical purity. The mechanism of the coupling reaction is discussed.

The authors report their experience with follow-up cytohistological examination of subclinical thoracic lesions in oncology by transparietal puncture with CAT-scanning localization in 170 patients. They detail a few special points concerning the material used and their techniques, in view of reducing the most common incidents and of managing the most severe complications. They analyze their results in two groups of patients, one investigated in a context of known malignancy and the other, with no history of malignancy in whom bronchoscopy, bronchial lavage and brushing were negative. They found an overall sensitivity and specificity of 86% and 100%, respectively, in the diagnosis of malignant disease. The method showed an efficacy of 83.5%. For the two populations, sensitivity was 84% and 87% respectively, and efficacy was 82 and 85% respectively. Thus, the results were better in the patients who had never received anticancer therapy. They also observed significant differences depending on whether the targets were mediastinal, pleuropulmonary or parietal. While the rapid diagnostic information appears invaluable in both groups of patients, in contrast, the small volume of the specimens, which may be hemorrhagic, necrotic, with more or less extensive fibrosis of the stroma, and the immaturity of certain tumors, sometimes make it impossible for the pathologist to give a precise diagnosis of the tumor other than the benign or malignant structural character of the lesion. This represents a significant obstacle in hematology for affections which, although non surgical, nevertheless require precise identification of the lesion for effective therapy. The elaboration of more effective sampling material, repeated punctures and immunohistoenzymatic analysis techniques would probably further improve the results of the method.