Conventional fascial technique versus mesh repair for advanced pelvic organ prolapse: Analysis of recurrences in treated and untreated compartments.

117 women with severe pelvic organ prolapse (POP; stage > 2) were enrolled to elucidate a 24-month outcome of POP surgery, using conventional or mesh repair with 3 techniques. 59 patients underwent conventional repair and 58 underwent mesh repair. Two types of mesh were used: a trocar-guided transobturator polypropylene (Avaulta, Bard Inc.) and a porcine dermis mesh (Pelvisoft, Bard Inc.). Women with recurrences, who underwent previous unsuccessful conventional repair, were randomised. Primary outcome was the evaluation of anatomic failures (prolapse stage > 1) in treated and untreated compartments. Anatomic failure was observed in 11 of 58 patients (19%; CI 8.9-29) in the mesh group and in 16 of 59 patients (27.1%; p value = 0.3) in the conventional group. 9 of 11 failures in the mesh group (15.5%; CI 6.2-24.8) were observed in the untreated compartment (de novo recurrences), 14.3% in Pelvisoft and 16.7% in Avaulta arm, while only 1 recurrence in the untreated compartment (1.7%) was observed in the conventional group (odds ratio 10.6, p = 0.03).

Low dose of fine particulate matter (PM2.5) can induce acute oxidative stress, inflammation and pulmonary impairment in healthy mice.

Air pollution is associated with morbidity and mortality induced by respiratory diseases. However, the mechanisms therein involved are not yet fully clarified. Thus, we tested the hypothesis that a single acute exposure to low doses of fine particulate matter (PM2.5) may induce functional and histological lung changes and unchain inflammatory and oxidative stress processes. PM2.5 was collected from the urban area of São Paulo city during 24 h and underwent analysis for elements and polycyclic aromatic hydrocarbon contents. Forty-six male BALB/c mice received intranasal instillation of 30 µL of saline (CTRL) or PM2.5 at 5 or 15 µg in 30 µL of saline (P5 and P15, respectively). Twenty-four hours later, lung mechanics were determined. Lungs were then prepared for histological and biochemical analysis. P15 group showed significantly increased lung impedance and alveolar collapse, as well as lung tissue inflammation, oxidative stress and damage. P5 presented values between CTRL and P15: higher mechanical impedance and inflammation than CTRL, but lower inflammation and oxidative stress than P15. In conclusion, acute exposure to low doses of fine PM induced lung inflammation, oxidative stress and worsened lung impedance and histology in a dose-dependent pattern in mice.

Beyond the expected: Identifying broad research priorities of researchers and the cystic fibrosis community.

The Cystic Fibrosis Foundation (CFF) supports research programs aimed at improving care and building a successful drug development pipeline. To ensure its research agenda meets the needs of the community it serves, the CFF sought community input into clinical research prioritization for topics not well-known as already being addressed by CFF-funded research. In 2018, clinical researchers, adults with CF, and family members were surveyed about a broad range of research topics that are perceived to receive less attention. We compared responses from researchers (n = 19) and community members (n = 135) and found groups aligned on their top three research priorities: 1) respiratory microorganism detection and treatment, 2) mental health, and 3) reducing treatment burden. We also explored whether or not those priorities align with the CFF research portfolio. Cognizance of researcher and community priorities can help inform clinical research endeavors to improve the health and well-being of people affected by CF.

Cognitive profile in Duchenne muscular dystrophy boys without intellectual disability: The role of executive functions.

The aim of our prospective observational study was to assess profiles of cognitive function and a possible impairment of executive functions in a cohort of boys with Duchenne muscular dystrophy without intellectual and behavior disability. Forty Duchenne boys (range of age: 6 years to 11 years and 6 months) were assessed by Wechsler Intelligence scale and battery of tests including tasks assessing working memory and executive functions (inhibition and switching, problem solving and planning). In our cohort some aspects of cognitive function were often impaired. These included multitasking, problem solving, inhibition and working memory necessary to plan and direct goal oriented behavior. Our results support the suggestion that aspects of cognitive function could be impaired even in boys without intellectual disability and support the hypothesis that executive functions may play an important role in specific aspects of cognitive impairment in Duchenne muscular dystrophy.

Prediction of high on-treatment platelet reactivity in clopidogrel-treated patients with acute coronary syndromes.

BACKGROUND: About 40% of clopidogrel-treated patients display high platelet reactivity (HPR). Alternative treatments of HPR patients, identified by platelet function tests, failed to improve their clinical outcomes in large randomized clinical trials. A more appealing alternative would be to identify HPR patients a priori, based on the presence/absence of demographic, clinical and genetic factors that affect PR. Due to the complexity and multiplicity of these factors, traditional statistical methods (TSMs) fail to identify a priori HPR patients accurately. The objective was to test whether Artificial Neural Networks (ANNs) or other Machine Learning Systems (MLSs), which use algorithms to extract model-like 'structure' information from a given set of data, accurately predict platelet reactivity (PR) in clopidogrel-treated patients. METHODS: A complete set of fifty-nine demographic, clinical, genetic data was available of 603 patients with acute coronary syndromes enrolled in the prospective GEPRESS study, which showed that HPR after 1month of clopidogrel treatment independently predicted adverse cardiovascular events in patients with Syntax Score >14. Data were analysed by MLSs and TSMs. ANNs identified more variables associated PR at 1month, compared to TSMs. RESULTS: ANNs overall accuracy in predicting PR, although superior to other MLSs was 63% (95% CI 59-66). PR phenotype changed in both directions in 35% of patients across the 3 time points tested (before PCI, at hospital discharge and at 1month). CONCLUSIONS: Despite their ability to analyse very complex non-linear phenomena, ANNs or MLS were unable to predict PR accurately, likely because PR is a highly unstable phenotype.

Widespread Focal Cortical Alterations in Autism Spectrum Disorder with Intellectual Disability Detected by Threshold-Free Cluster Enhancement.

BACKGROUND AND PURPOSE: In the past decades, a large body of work aimed at investigating brain structural anomalies accrued in autism spectrum disorder. Autism spectrum disorder is associated with intellectual disability in up to 50% of cases. However, only a few neuroimaging studies were conducted in autism spectrum disorder with intellectual disability, and none of them benefited from a nonsyndromic intellectual disability control group. MATERIALS AND METHODS: We performed a voxelwise investigation of the structural alterations in 25 children with autism spectrum disorder with intellectual disability by comparing them with 25 typically developing children and 25 nonsyndromic children with an intellectual disability. Besides a classic voxel-based morphometry statistical approach, the threshold-free cluster enhancement statistical approach was adopted. RESULTS: Classic voxel-based morphometry results did not survive family-wise error correction. The threshold-free cluster enhancement-based analysis corrected for family-wise error highlighted the following: 1) widespread focal cortical anomalies and corpus callosum alteration detected in autism spectrum disorder with intellectual disability; 2) basal ganglia and basal forebrain alteration detected both in autism spectrum disorder with intellectual disability and in nonsyndromic intellectual disability; and 3) differences in the frontocingulate-parietal cortex between autism spectrum disorder with intellectual disability and nonsyndromic intellectual disability. CONCLUSIONS: The present study suggests that the frontocingulate-parietal cortex may be the eligible key region for further investigations aiming at detecting imaging biomarkers in autism spectrum disorder with intellectual disability. The detection of structural alterations in neurodevelopmental disorders may be dramatically improved by using a threshold-free cluster enhancement statistical approach.

Neuropsychological testing may predict early progression of asymptomatic adrenoleukodystrophy.

OBJECTIVES: To investigate the correlation between neuropsychological and MRI findings in children with the childhood cerebral (CCALD) and asymptomatic forms of X-linked adrenoleukodystrophy (ALD) and to identify early cognitive markers that may predict disease progression in asymptomatic children with ALD. BACKGROUND: The few published neuropsychological studies on CCALD suggest a correlation between the pattern of cognitive deficit and lesion site; however, neuropsychological performance in asymptomatic children with ALD has not been investigated. METHODS: The authors assessed cognitive function and cerebral MRI findings in seven CCALD and eight asymptomatic ALD children. RESULTS: The CCALD children's cognitive skills were severely compromised, especially Wechsler and executive functions. Visual perception, short-term memory, and language were generally preserved, except that naming was severely impaired. All had extensive posterior white matter deterioration. The asymptomatic children had relatively intact neuropsychological performance, but their verbal fluency was compromised and naming severely impaired. All except one had mild white matter alterations. For all the children, the majority of neuropsychological test performance correlated significantly with extent of white matter lesions. CONCLUSIONS: The pattern of cognitive deterioration in children with CCALD and the significant correlation of neuropsychological test performance with extent of white matter lesions indicate a white matter dementia similar to that observed in adults with demyelinating diseases. The deficits found in asymptomatic children, despite their normal intelligence, suggest that careful neuropsychological investigation can identify early signs of malfunction. These may be markers of disease progression useful for selecting children for bone marrow transplant, although this will require confirmation by prospective longitudinal studies.

Intrathecal methotrexate affects cognitive function in children with medulloblastoma.

BACKGROUND: Cognitive impairment occurs after malignant brain tumor treatment in children, following brain radiotherapy and systemic and intrathecal chemotherapy. OBJECTIVES: 1) To compare two groups of children who underwent surgery for cerebellar medulloblastoma with their cousins and siblings, assessing intelligence, executive function, attention, visual perception, and short-term memory. Both groups were treated with the same combined radiotherapy-chemotherapy, but differed in that only one group received intrathecal methotrexate (MTX+). 2) To relate these measures to MRI findings (leukomalacia). RESULTS: The two groups performed worse than their control subjects in all tests. The MTX+ group younger than 10 years performed significantly worse in all tests, particularly executive ones. The group older than 10 years performed significantly worse only in short-term memory. Younger patients without MTX performed significantly worse than controls only in some neuropsychological measures; there were no differences between older patients and control subjects. Only in the MTX+ group was there a direct correlation between extent of leukomalacia and performance in some tests. CONCLUSIONS: The administration of intrathecal methotrexate to children with medulloblastoma worsens the cognitive deficits induced by chemotherapy and radiotherapy. The use of intrathecal methotrexate in the treatment of medulloblastoma and other malignancies should be reassessed.

Language deficits in a child with omolateral (left) temporo-basal and cerebellar lesions.

We report the case of an 8-year-old boy with two distinct brain lesions, probably hamartomas or low grade gliomas: one in the left basal temporal region, with involvement of the fusiform gyrus, the other in the white matter of the left cerebellar hemisphere. Both lesions were diagnosed at seven, when NMR was performed because of partial complex seizure. A mild delay in the first language acquisition and a long-lasting difficulty in word retrieval were reported. On neuropsychological testing, language was impaired more in production tasks than in comprehension ones, with severe deficit in word finding. The etiological role of the two different lesions is discussed in relation to experimental evidence of the existence of a distinct language area in the basal temporal region (fusiform gyrus).

Late effects of unilateral brain lesions sustained before and after age one.

Forty-eight children with unilateral cerebral lesions, incurred before or after the first year of life, were given the Wechsler Intelligence Scale for Children, with an average delays of 4 and 8 1/2 yr for the late and early injuries, respectively. Thirty-one of their siblings were chosen as controls. Results are as follows: early and late right-hemisphere lesions significantly lower only Performance IQ. Early left lesions impair equally Verbal and Performance IQ, while late left-hemisphere lesions do not significantly affect Verbal or Performance IQ relative to controls.

Influenza circulating strains in Argentina exhibit differential induction of cytotoxicity and caspase-3 in vitro.

BACKGROUND: Human influenza infections are a significant cause of morbidity worldwide. Though damage to the respiratory epithelium and has been related to apoptosis, which occurs subsequent to influenza virus infection, little information is available regarding cell cytotoxicity of human strains. OBJECTIVE: To study cytotoxicity performed in vitro by various circulating strains in Argentina. The study sample consisted of three vaccine strains (H1N1, H3N2, and B) administered during 1999-2000 in South America and three strains isolated from clinical samples, one, NAC (H1N1) obtained from an adult inpatient with human pneumonia; and the other two (T) and (T2) (H3N2) with influenza syndrome. Viral antigen was detected by an immunofluorescence test, conducted prior to viral isolation in MDCK cells. Strains were subtyped by the hemmaglutination inhibition test. Cytotoxic properties were determined by lactate dehydrogenase reaction (LDH), crystal violet staining and Hoechst staining. Caspase-3 activity, morphological changes of apoptosis, and viral yields were measured in MDCK infected cells. RESULTS AND CONCLUSIONS: Cells infected by each of the strains exhibited apoptosis morphology by Hoechst staining and caspase-3 activity was high for both H1N1 strains. Further, high levels of LDH activity were detected for NAC and H3N2 strains tested, indicating the possible role of different viral proteins or functions on cell cytotoxicity. The NAC strain, isolated from human pneumonia and antigenically related to A/New Caledonia /20/99 (H1N1), was the highest cytotoxic strain and an excellent inducer of caspase-3 activity. In turn, no parameter was related to different viral yields. We conclude that human strains studied in this paper may be useful tools in the characterization of molecular determinants involved in viral cytopathogenicity.

The cerebellar contribution to language and sequential functions: evidence from a child with cerebellitis.

We report the case of a 4 years and 2 months old girl, whose development was normal before she suffered from severe viral cerebellitis. When she recovered from the acute phase, a complete loss of speech was evident, although language comprehension was not impaired. Mutism disappeared after about two weeks, giving way to the aphonic utterance of a few words. After three months, her speech was slow and monotonous, without phonetic disturbances. She could only produce very simple and incomplete sentences in both spontaneous and constrained situations and she was able to maintain discourse sequentiality only under continuous guidance. No deficit in single-word recognition or naming was detected. Her sentence reproduction was good, while verbal fluency was very poor when no cue was given, but was normal with category cues. Her intelligence was within the normal range, but activities requiring programming, particularly those involving sequencing, were very defective. The patient's impairment is attributed to the failure of the cerebellar-frontal loops to activate strategies involved in processing and programming verbal and sequential functions.

Visuospatial judgment: a cross-national comparison.

Two samples of American and Italian 8 to 12 year-old children were compared for their performance on the Judgment of Spatial Orientation Test. No group difference emerged and, consequently, the same normative standards for performance can be applied in both countries. In both groups males performed better than females.

Stereotactically guided transfrontal removal of intraventricular midline tumors in children. Neurosurgical and neuropsychological considerations.

Five children with supratentorial intraventricular midline cerebral tumors were operated on using a stereotactically guided transfrontal approach. Assisted by a three-dimensional graphic reconstruction of cerebral anatomy, the surgeon was able to reach and remove the lesion with minimal damage to healthy parenchyma. Neurosurgical and neuropsychological evaluation of the results suggests that this surgical approach is a valid alternative to the transcallosal route. This image-based intraoperative guidance is as effective as landmark-oriented surgery, which requires section of the corpus callosum, possibly leading to neuropsychological deficits, particularly in the pediatric age group.

Radiosurgery for cerebral AVMs in children and adolescents: the neurobehavioral outcome.

Eight patients, ranging in age from 9 to 18 years, were treated for arteriovenous malformations using gamma knife radiosurgery and were evaluated an average of 6 years after treatment to record potential effects of radiosurgery on cognitive and neuropsychological performance. Tests for general intelligence, nonverbal intelligence, memory and its components, and attention performance were administered to patients and compared with test results of age-matched siblings or first cousins. No statistically significant difference was found between the performance of patients and controls in any of the tests administered. Additionally, a specially designed questionnaire completed by the patients, their parents, and their teachers revealed that the patients' emotional and relational behavior was stable and unchanged after treatment. No correlation was found between the neurocognitive test performance and the lesion volumes irradiated, but the lesion site was found to contribute to the type of deficit recorded after treatment. The less invasive nature of the radiosurgical approach, combined with the brevity or absence of hospitalization, presumably contributed to the patients successful physical, mental, and emotional recovery.

Carbamazepine withdrawal in children with previous symptomatic partial epilepsy: effects on neuropsychologic function.

Neurocognitive performance was evaluated in seven children with symptomatic partial epilepsy prior to, and at least 12 months after, discontinuation of carbamazepine. The patients treated with carbamazepine monotherapy were seizure-free for at least 2 years and without electroencephalographic anomalies for at least 1 year. Results indicated that carbamazepine at therapeutic levels does not affect intellectual, memory, or attentional functions, or more complex frontal functions. Nevertheless, after therapy withdrawal scores on frontal function tests used in this study improved significantly. This suggests that these functions could have been better without carbamazepine therapy. The fact that carbamazepine decreases neuron membrane excitability and could reduce the information circuity, particularly in the frontal areas, is offered as a possible explanation. Further studies on larger samples using the same design are required to validate these results.

Papillitis as an onset sign of Leber's hereditary optic neuropathy: a case report.

Leber's hereditary optic neuropathy is a maternally transmitted disease resulting from a point mutation in mitochondrial (mt) DNA. In this report we describe a case of Leber's disease with typical clinical findings but atypical ophthalmoscopic presentation. A 14-year-old boy developed severe loss of vision acuity in the left eye, with only partial recovery, followed 4 months later by the same symptoms in the right eye. Fundoscopic examination showed hyperemic papilla on the right eye and optic disc pallor on the left eye. Polymerase chain reaction analysis of lymphocytic mt-DNA revealed a point mutation at 11778. Leber's disease should be considered in young patients (not always male) with sudden visual loss and simple papillary involvement at fundoscopic examination but without the typical telangiectatic microangiopathy.

Discontinuation of phenobarbital in children: effects on neurocognitive behavior.

Neurocognitive performances were evaluated in 9 children with different types of epilepsy prior to and at least 6 months after discontinuation of phenobarbital. The patients treated with phenobarbital monotherapy were seizure free for at least 2 years, without electro-encephalographic anomalies for at least 1 year. Results indicated that phenobarbital at low therapeutic doses causes attentional and memory deficits, reversible after therapy discontinuation. Further research utilizing the same design is needed on larger samples in order to confirm our results.

A case of 3-methylglutaconic aciduria misdiagnosed as cerebral palsy.

3-Methylglutaconic aciduria is a rare hereditary metabolic disorder characterized by increased urinary excretion of 3-methylglutaconic and 3-methylglutaric acids. Four clinical forms are recognized. This study presents the case of a 5-year-old male with type IV 3-methylglutaconic aciduria, initially diagnosed as "static encephalopathy." The slow evolution and other clinical characteristics, together with cerebral magnetic resonance imaging (MRI) findings, eventually directed the diagnosis to organic aciduria that was confirmed by urine test. This study proposes that the clinical criteria for childhood cerebral palsy should be rigorously respected; neuroimaging studies, particularly MRI, should be conducted to confirm the diagnosis, especially in atypical cases.