ASSESSMENT OF NEONATAL AND MATERNAL COMPLICATIONS IN PREGNANT WOMEN WITH GESTATIONAL DIABETES IN THE IRANIAN POPULATION.

Context: Gestational diabetes mellitus (GDM) is one of the most common complications during pregnancy. It is also a growing problem worldwide and is associated with many maternal and fetal complications during and after pregnancy. Objective: This study aimed to investigate the neonatal and maternal complications of gestational diabetes in the Iranian population of pregnant women. Design: This prospective cohort study was carried out on the health assessment data of pregnant women in the age range of 18-45 years who were referred to health centers affiliated with Mashhad University of Medical Sciences, Mashhad, Iran, from March 2019 to September 2020. Subjects and Methods: Overall, 2,500 pregnant women with GDM and 7,700 healthy pregnant women were enrolled in the GDM and healthy groups, respectively. Individuals' data were recorded in an electronic health record system (SINA System) and were later collected and analyzed. Results: Significant between-group differences were observed in terms of cesarean delivery risk, hypertension, fetal macrosomia, preeclampsia, preterm birth, fetal birth weight, and neonatal icterus in GDM and non-GDM groups. However, no significant differences were found in terms of stillbirth, and low birth weight between the two groups. Based on the logistic regression model, GDM significantly increased the risk of cesarean delivery, fetal macrosomia, and neonatal icterus. Conclusions: The fetal macrosomia leading to the cesarean delivery, and neonatal icterus were determined as the significant complications of GDM in the Iranian population. These results can provide valuable insight into healthcare planning.

A multicenter, observational, prospective study of self- and parent-reported quality of life in adolescent multiple sclerosis patients self-administering interferon-ß1a using RebiSmart™-the FUTURE study.

Besides the impact of disease per se, the use of immunomodulatory therapies in adolescents with relapsing-remitting multiple sclerosis (RRMS) may have an effect on quality of life (QL). The FUTURE (Quality of liFe in adolescent sUbjecTs affected by mUltiple sclerosis treated with immunomodulatoRy agEnt using self-injecting device) study was designed to evaluate the changes in QL of Italian adolescents with RRMS receiving treatment with IFN-ß1a (Rebif; 22 µg), administered subcutaneously three times weekly using the RebiSmart™ electronic autoinjection device over a 52-week period. Fifty adolescents with RRMS were enrolled and 40 completed the study. Changes from baseline to end of treatment (EoT) in adolescent self-reported and parent-reported QL were assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL), which has been validated for use in pediatric MS and for which an Italian version is available. The adolescent self-reported total PedsQL4.0 score and all of its subscales tended to increase from baseline to EoT, the only exception being "Emotional functioning." In parent-reported measures, the total PedsQL4.0 score increased significantly from baseline to EoT (+ 5.27 points, p = 0.041). Significant increases were also evident for parent-reported "Psychosocial health summary score" (+ 5.90 points; p = 0.015) and "School functioning" (+ 7.84 points; p = 0.029). Our results indicate that adolescents with RRMS using the electronic injection device RebiSmart™ for self-administration of Rebif® can experience long-term improvements in QL.

Cortical lesions in children with multiple sclerosis.

OBJECTIVE: Double inversion recovery (DIR) sequences have improved the detection of cortical lesions (CLs) in adult patients with multiple sclerosis (MS). We evaluated the presence and frequency of CLs in pediatric patients with relapsing-remitting MS (RRMS) in comparison to adult patients with MS with the same clinical phenotype. METHODS: Using a 3.0-T scanner, brain DIR, dual-echo, and 3-dimensional T1-weighted scans were acquired from 24 pediatric patients with RRMS, 15 adult patients with RRMS, and 10 pediatric healthy controls. CLs and white matter (WM) lesions were identified, and their volumes measured. Brain gray matter and WM volumes were also calculated. Between-group comparisons were performed using χ(2), Mann-Whitney, and analysis of variance tests. Poisson regressions for count data were used to model the number of lesions of the 2 groups of patients. RESULTS: Compared to adults, pediatric patients had shorter disease duration and lower disability. WM lesion number and volume did not differ between pediatric and adult patients with MS. CLs were detected in 2 (8%) pediatric and 10 (66%) adult patients. Median CL volume was lower in pediatric than adult patients with RRMS (p = 0.0003). Regression analysis showed that pediatric patients had a lower number of CLs than adults (p = 0.0003), after adjusting for age, gender, Expanded Disability Status Scale score, and disease duration. CONCLUSION: CLs are rare in pediatric patients with MS. Since pediatric patients with MS have a clinical onset closer to the biological onset of the disease than adult patients with MS, our findings indicate that CL formation is likely not to be an initial event in this disease.

Ticks and Lyme borreliosis in an alpine area in northeast Italy.

A 2-year study was conducted in a mountainous area of northeast Italy to evaluate the occurrence and distribution of ticks, as well as to assess the prevalence of the spirochaete Borrelia burgdorferi sensu lato. All ticks collected were Ixodes ricinus L. (Parasitiformes: Ixodidae). In general, most nymphs and adult ticks were collected from April to July. Tick density was highly variable among sites; however, two areas with different infestation levels were recognized. Prevalences of B. burgdorferi s.l. in nymphal stages were rather variable between sites; overall the prevalence of infected nymphs in the whole area was slightly higher than 20%. The prevalence of B. burgdorferi s.l. in nymphs does not seem to be correlated with nymph density. The correlation between the incidence of Lyme borreliosis (reported human cases/1000 inhabitants/year) and Borrelia prevalence in nymphs was not significant, although a significant correlation was found between borreliosis incidence and nymph density.

Selection of Apis mellifera workers by the parasitic mite Varroa destructor using host cuticular hydrocarbons.

The parasitic mite, Varroa destructor, is the most important threat for apiculture in most bee-keeping areas of the world. The mite is carried to the bee brood cell, where it reproduces, by a nurse bee; therefore the selection of the bee stage by the parasite could influence its reproductive success. This study investigates the role of the cuticular hydrocarbons of the European honeybee (Apis mellifera) in host-selection by the mite. Preliminary laboratory bioassays confirmed the preference of the varroa mite for nurse bees over pollen foragers. GC-MS analysis of nurse and pollen bees revealed differences in the cuticular hydrocarbons of the two stages; in particular, it appeared that pollen bees have more (Z)-8-heptadecene than nurse bees. Laboratory experiments showed that treatment of nurse bees with 100 ng of the pure compound makes them repellent to the varroa mite. These results suggest that the mite can exploit the differences in the cuticular composition of its host for a refined selection that allows it to reach a brood cell and start reproduction. The biological activity of the alkene encourages further investigations for the development of novel control techniques based on this compound.

Evidence of thalamic gray matter loss in pediatric multiple sclerosis.

OBJECTIVE: We used voxel-based morphometry (VBM) to assess the pattern of regional gray matter (GM) loss in patients with pediatric multiple sclerosis (MS) and its relation with the Expanded Disability Status Scale (EDSS) score, disease duration, and the extent of T2 lesion load (LL). METHODS: From 28 patients with pediatric relapsing-remitting MS (16 girls; mean age = 14.4 years, range = 7 to 16 years) and 21 matched controls, dual-echo and three-dimensional T1-weighted magnetization prepared rapid acquisition gradient echo sequences were acquired. T2 LL was measured using a local thresholding segmentation technique. Data were analyzed using an optimized VBM analysis and statistical parametric mapping. RESULTS: In pediatric patients with MS, mean brain T2 LL was 7.8 mL +/- 11.3. Intracranial volume did not differ between patients and controls. Compared to controls, patients with pediatric MS had significant GM loss in the thalamus, bilaterally, which was significantly correlated with T2 LL (r = -0.80 for the right thalamus, r = -0.74 for the left thalamus, p < 0.05, corrected for multiple comparisons). No correlation was found between thalamic GM loss, disease duration, and disability. CONCLUSIONS: In patients with pediatric multiple sclerosis (MS), differently from what happens in adult-onset MS, gray matter (GM) atrophy seems to involve the thalamus only, with sparing of the cortex and other deep GM nuclei. The correlation found between atrophy and T2 lesion load suggests transsynaptic and Wallerian degenerations as the most likely substrate of tissue loss in the thalamus of these patients.

Treatment of early-onset multiple sclerosis with intramuscular interferonbeta-1a: long-term results.

The objective was to evaluate the safety, tolerability and effectiveness of intramuscular (IM) interferon beta-1a (IFNbeta-1a; Avonex, Biogen) 30 mg once a week in patients with onset of symptoms of multiple sclerosis (MS) in childhood or adolescence. Patients with a diagnosis of definite MS according to McDonald's criteria, relapsing course according to Lublin's criteria, onset of symptoms of MS before 16 years of age, and who had received IM IFNbeta-1a therapy before 16 years of age were eligible for the study if they had a pretreatment and treatment duration of at least 6 months. Clinical and laboratory evaluations were performed every 3 months. A total of 52 patients were identified as receiving treatment with IM IFNbeta-1a 30 mg once a week before 16 years of age. Mean age at onset of symptoms of MS was 11.7+/-2.7 years, mean disease duration was 25.9+/-30.3 months, mean annualised relapse rate was 1.9+/-1.1 and mean Expanded Disability Status Scale (EDSS) score was 1.5+/-1.1. After a mean (+/-SD) treatment duration of 42.9+/-19.9 months, annualised relapse rate decreased to 0.4+/-0.5. Final EDSS score was 1.3+/-1.1. Adverse events were recorded for 35 (67%) patients (flulike syndrome, 33%; headache, 29%; myalgia, 21%; fever, 11%; fatigue, 6%; nausea and vomiting, 6%; and skin reaction, 4%); most were transient. IM IFNbeta-1a was effective and well tolerated in these paediatric patients with MS.

Disease-modifying drugs in childhood-juvenile multiple sclerosis: results of an Italian co-operative study.

OBJECTIVE: Immunomodulatory drugs (IDs) (interferon beta (IFNgamma) and glatiramer acetate (GA)) reduce relapse rate and disease progression in relapsing remitting multiple sclerosis (RRMS) but extensive data are not available on the effectiveness and tolerability of these drugs in childhood or adolescence. The aim of this study was to evaluate the impact of IFNbeta and GA in MS patients treated before 16 years of age. METHODS: A research group (Immunomodulatory Treatment of Early onset MS (ITEMS)) was promoted in Italy to collect a large series of patients affected by clinically definite and RRMS and treated with IDs before 16 years of age. Fifteen centres recognized subjects suitable for inclusion: 76 patients (52 females) were collected with a mean age at onset of 12.4 (SD 2.5) years, a mean disease duration of 18.6 (SD 14.7) and a relapse rate of 3.1 (SD 2.9). RESULTS: Results were evaluated in 65 (45 females) subjects with a pretreatment and a treatment duration >3 months: 38 were treated with IFNbeta-1a once weekly (Avonex), 18 with IFNbeta three times weekly (16 with Rebif, 2 with Betaferon) and nine with GA (Copaxone). The mean pretreatment period was respectively 20, 18 and 9.2 months. The treatment duration lasted respectively 23.3, 40.7 and 33.3 months. The mean annualized relapse rate decreased dramatically during the treatment: from 2.4 to 0.4 in the Avonex group, from 3.2 to 0.8 in the Rebif-Betaferon group and from 2.8 to 0.25 in the GA group. The mean final EDSS scores were respectively (in brackets the initial scores): 1.3 (1.4), 1.6 (1.8) and 0.6 (1.1). In the whole group, the final score was unchanged or reduced in all subjects except eight. Clinical side effects were recorded in 41/65 subjects (mainly in subjects treated with IFNbeta), abnormal laboratory findings were observed in 13/65 subjects: they were transient in most cases. IFNgamma was stopped in six cases: in four because of inefficacy and in two cases because of side effects. CONCLUSIONS: Sixty-five clinically definite MS subjects were treated during childhood or adolescence with IDs. The treatment reduced the relapse rate and the progression of the disease in most cases. Side effects were common in subjects treated with IFNbeta but were well tolerated in most cases.

Development of a standard set of microsatellite reference alleles for identification of grape cultivars.

In order to investigate the comparability of microsatellite profiles obtained in different laboratories, ten partners in seven countries analyzed 46 grape cultivars at six loci (VVMD5, VVMD7, VVMD27, VVS2, VrZAG62, and VrZAG79). No effort was made to standardize equipment or protocols. Although some partners obtained very similar results, in other cases different absolute allele sizes and, sometimes, different relative allele sizes were obtained. A strategy for data comparison by means of reference to the alleles detected in well-known cultivars was proposed. For each marker, each allele was designated by a code based on the name of the reference cultivar carrying that allele. Thirty-three cultivars, representing from 13 to 23 alleles per marker, were chosen as references. After the raw data obtained by the different partners were coded, more than 97% of the data were in agreement. Minor discrepancies were attributed to errors, suboptimal amplification and visualization, and misscoring of heterozygous versus homozygous allele pairs. We have shown that coded microsatellite data produced in different laboratories with different protocols and conditions can be compared, and that it is suitable for the identification and SSR allele characterization of cultivars. It is proposed that the six markers employed here, already widely used, be adopted as a minimal standard marker set for future grapevine cultivar analyses, and that additional cultivars be characterized by means of the coded reference alleles presented here. The complete database is available at http://www.genres.de/eccdb/vitis/ Cuttings of the 33 reference cultivars are available on request from the Institut National de la Recherche Agronomique Vassal collection (didier.vares@ensam.inra.fr).

Neuromyelitis optica in a child with atypical onset and severe outcome.

We report on a seven-year-old boy with inflammatory relapsing-remitting CNS disease, involving the optic nerves and spinal cord, with increasingly severe sequelae after each relapse. Clinical course, neuroimaging and laboratory findings were consistent with neuromyelitis optica. Biopsy of leptomeninges and underlying nervous tissue showed increased vascularization and thickened hyalinized vessel walls, reported as suggestive for neuromyelitis optica. Clinical features at onset were atypical, rendering the case highly unusual and the diagnosis tentative.

Prospective study of multiple sclerosis with early onset.

Fifty-four subjects (36 females and 18 males) affected by clinically definite multiple sclerosis (MS) and with onset of the disease at 15 years of age or before were prospectively studied in five Italian MS centres. Female/male ratio was 4.7 in subjects with age > or = 12 years, suggesting a role of hormonal changes in triggering MS onset The mean follow-up duration was 10.9+/-5.6 years. The functional systems more frequently involved at onset were the pyramidal and brainstem (both in 28% of cases). The onset was monosymptomatic in 31 subjects (57%). The course was relapsing-remitting in 39 subjects (72%) and relapsing-progressive in 15 (28%). Disability was assessed by the Expanded Disability Status Scale (EDSS): the mean score after 8 years of follow up was 3.5 (+/-2.5). The score was <4 in 68% of cases, between 4 and 6 in 8% of cases, >6 in 24% of cases. Disability after 8 years was highly predicted by disability in the first year (p=0.008). There was a tendency to a worse prognosis in relation to the number of relapses in the first 2 years (p=0.08). The outcome was not influenced by the characteristics of symptoms at onset age and gender.

The human glycine receptor beta subunit gene (GLRB): structure, refined chromosomal localization, and population polymorphism.

The glycine receptor of the human CNS comprises ligand-binding alpha 1 and structural beta subunits encoded by the GLRA1 and GLRB genes, respectively. Screening of a human hippocampal cDNA library resulted in the identification of the novel subunit transcript beta B, differing in the 5'-UTR. Analysis of the genomic organization of GLRB showed that the coding region is distributed over nine exons, highly homologous to the GLRA1 gene. By in situ hybridization, the chromosomal localization of GLRB was refined to band 4q31.3. Based on the identical phenotypes of mouse lines carrying mutant alleles of the alpha 1 and beta subunit genes, GLRB was assumed to be a candidate gene for those cases of hyperekplexia that cannot be associated with mutations of GLRA1. Therefore, flanking intronic sequences were determined, and DNA samples from more than 30 index patients were subjected to SSCP screening of the entire GLRB coding region. A polymorphism in exon 8 was found both in the normal population and in families affected by hyperekplexia, although no coding mutation was detectable.

Intelligence outcome in children with shunted hydrocephalus of different etiology.

Children with shunted hydrocephalus of differing etiologies were assessed. There was a more selective loss of non-verbal than of verbal intelligence. The verbal and visuo-perceptual abilities were affected by different sets of variables. Variables related to the hydrocephalus had no effects, while associated supratentorial malformations significantly affected non-verbal functions.

Hemispheric specialization in children with unilateral epileptic focus, with and without computed tomography-demonstrated lesion.

We evaluated 24 testable children with unilateral epileptic foci, with and without radiologically demonstrable lesions, to determine if the normal pattern of cerebral dominance is changed by the presence of an epileptic focus. Verbal and figural stimuli were presented tachistoscopically to the right and left visual hemifields to investigate the specific abilities of the two hemispheres. Three blocks of stimuli consisting of two-letter patterns, three-letter patterns, and meaningful two-syllable words were used as verbal stimuli to assess the abilities of the left hemisphere. A test consisting of localizing a dot on a 3 x 3 matrix was used to assess the abilities of the right hemisphere. Six normal children were chosen as controls. In all groups, specialization of the epileptic hemisphere was lost. The presence or absence of a radiologically demonstrable lesion did not influence this pattern.

Hemifacial spasm in a child.

Hemifacial spasm in a 10-year-old child is herein reported. Computed tomography and angiography were normal. Magnetic resonance imaging showed an anomalous vascular structure, probably a redundant loop arising from AICA or PICA, which was identified at surgery. The spasm, presumably due to vascular compression at the root entry zone of the right facial nerve, promptly and completely remitted after surgical decompression, without functional deficits. Atypical clinical features, as well as pre- and postoperative neurophysiological findings supporting the microvascular compression theory, are discussed.

Combined treatment modality for medulloblastoma in childhood: effects on neuropsychological functioning.

8 long-surviving children, treated for medulloblastoma with combination radiotherapy and chemotherapy after surgery were examined in order to assess general intelligence, immediate attention and prolonged attention. Their siblings or first cousins were selected as controls. The children with medulloblastoma performed significantly worse than their peers, both in intelligence tests and attention tests. A trend towards a positive correlation between age at the start of treatment and IQs was confirmed in our study, while there was no evidence of a correlation between IQs and time elapsed from therapy. The role of chemotherapy, radiotherapy and their combination effect in producing neuropsychological sequelae is discussed.

Impairment of neuropsychological functions in children with medulloblastomas and astrocytomas in the posterior fossa.

Neuropsychological impairment after removal of posterior fossa tumors is a recurrent issue in child neuropsychology and neurosurgery. The aim of this study was to assess verbal and performance intelligence, as well as immediate and sustained attention, in children with medulloblastoma or astrocytoma operated on for total removal of the lesion. Surgical treatment of medulloblastoma was always followed by chemoradiotherapy. Siblings of both tumor groups (without a history of neurological disease, even suspected) were examined as controls. The results were as follows: the cognitive performances were significantly poorer than the controls in both groups; the children with medulloblastoma scored below normal. Attention deficits were present in both groups as well when the usual clinical tests were used. When assessed by means of computerized methodology, the same function was normal. Considering that both groups of children underwent the same surgical treatment and all had hydrocephalus, the severe intellectual impairment reported only in patients with medulloblastoma can be ascribed to chemoradiotherapy. In contrast, the attention deficits present in both groups could be ascribed to the proximity of lesions to the ascending activating system. Malfunctioning of the activating system seems to be bypassed by the computerized administration of stimuli, which supplies motivation and kindles attention.