Neridronate for transient osteoporosis of the hip in a child.

Transient osteoporosis of the hip (TOH) is usually reported in middle-aged men or during pregnancy as a benign self-limiting condition. Nevertheless, its impact on quality of life in terms of pain and disability is considerable. Also, it can lead to insufficiency fractures or, more rarely, evolve into osteonecrosis. This condition is anecdotally described in the pediatric age and very little is known about how it may affect the growing bone. We herein describe a case of TOH in a 10-year-old child treated at our pediatric rheumatology service and summarize the pediatric cases of TOH previously reported in literature. There are two points of interest in our case report, the first one being the unusual complication of TOH with a femoral physis fracture and the second the complete recovery after the off-label therapy with bisphosphonates. We suggest that interventional medical treatment could be considered in selected cases of juvenile TOH, to prevent any possible irreversible damage on the femoral physis. As far as we know, this is the first report of neridronate employment in children affected by TOH.

Non-nursing tasks as experienced by nurses: a descriptive qualitative study.

BACKGROUND: Different concepts have been used to date (e.g. non-nursing tasks, organizational work) to define tasks performed by clinical nurses other than nursing care. However, the true essence of nursing work is still poorly understood mostly because nurses are lacking an appropriate lexicon to describe their practice. AIMS: To describe non-nursing tasks as experienced by nurses, exploring antecedents and consequences as perceived in daily practice. METHODS: A descriptive qualitative study from 2015 to 2016. A purposeful sample of nurses was approached. Semi-structured interviews were used, and content analysis was performed on audio-recorded and verbatim-transcribed interviews. FINDINGS: A total of 22 nurses participated, the majority of whom were female (16; 72.7%) and their average age was 42.6 years. The concept of 'Non-nursing tasks' is limited in describing what nurses experience in daily practice; the concept of 'Being out of the nursing role' emerged as being fully descriptive of the nurses' experience and this can occur in two dimensions: outside and inside the role of other healthcare professions. The first dimension includes administrative work separating nurses from patients. The second dimension was reported to happen in proximity to patients but in three different directions towards professions requiring: (a) less education (e.g. healthcare assistants), (b) the same amount of education at university level (e.g. physiotherapists), and (c) higher education at university level as compared to nurses, thus performing activities expected by physicians. Antecedents of 'Being out of the nursing role' have been identified at the organizational, individual and educational levels; their consequences have been reported at the patient, professional and organizational levels. CONCLUSION: Nurses play various non-nursing roles, below, above and in the horizontal levels, both inside and outside other healthcare professionals' role, mainly as a result of their felt moral obligation to offer the best to their patients, the organization's demand to nurses and the imprinting of nursing education. IMPLICATIONS FOR NURSING/HEALTH POLICY: Strategies at the nursing professional and policy levels are needed aimed at (a) supporting nurses in optimizing their professional identity, (b) sharing their sense of moral obligation towards patients with other healthcare professionals, and (c) implementing models of care based on interprofessional cooperation.

Clinical dissection of childhood occipital epilepsy of Gastaut and prognostic implication.

BACKGROUND AND PURPOSE: Our aim was to describe the clinical and electrical features and the long-term evolution of childhood occipital epilepsy of Gastaut (COE-G) in a cohort of patients and to compare long-term prognosis between patients with and without other epileptic syndromes. METHODS: This was a retrospective analysis of the long-term outcome of epilepsy in 129 patients with COE-G who were referred to 23 Italian epilepsy centres and one in Austria between 1991 and 2004. Patients were evaluated clinically and with electroencephalograms for 10.1-23.0 years. The following clinical characteristics were evaluated: gender, patient age at seizure onset, history of febrile seizures and migraine, family history of epilepsy, duration and seizure manifestations, circadian distribution and frequency of seizures, history of medications including the number of drugs, therapeutic response and final outcome. RESULTS: Visual hallucinations were the first symptom in 62% and the only manifestation in 38.8% of patients. Patients were subdivided into two groups: group A with isolated COE-G; group B with other epileptic syndromes associated with COE-G. The most significant (P < 0.05) difference concerned antiepileptic therapy: in group A, 45 children responded to monotherapy; in group B only 15 children responded to monotherapy. At the end of follow-up, the percentage of seizure-free patients was significantly higher in group A than in group B. CONCLUSIONS: Childhood occipital epilepsy of Gastaut has an overall favourable prognosis and a good response to antiepileptic therapy with resolution of seizures and of electroencephalogram abnormalities. The association of typical COE-G symptoms with other types of seizure could be related to a poor epilepsy outcome.

Efficacy and tolerability of add-on lacosamide in children with Lennox-Gastaut syndrome.

OBJECTIVE: Available data on the efficacy of lacosamide in children with Lennox-Gastaut syndrome (LGS) are scarce and controversial. We present our experience with lacosamide therapy in children affected by LGS. MATERIAL AND METHODS: Medical charts of all children affected by LGS receiving oral lacosamide adjunctive therapy in six paediatric neurology centres were retrospectively evaluated. Efficacy was determined according to the frequency of countable seizures during the 4 weeks prior to treatment and the frequency in the last 4 weeks of observation. Patients whose seizure frequency was reduced by at least 50% were defined as responders. RESULTS: Eighteen children (mean age 12.3 years) were identified. After a mean follow-up period of 9 months, 33% of patients were responders. None of them was seizure-free during the study period. The overall seizure reduction rate was 29%. The percentage reductions from baseline in tonic seizures and drop-attacks rates were 31% and 20%, respectively. Adverse reactions occurred in 44% of patients. The drug was discontinued in four (22%) patients because of increased seizure frequency (three cases) and walking instability (another patient). CONCLUSIONS: A third of children with LGS were responders after lacosamide adjunctive therapy. Although caution is still necessary when the drug is used in children with LGS, our preliminary observations suggest that lacosamide might be effective and represent a possible therapeutic option in children affected by LGS.

Anticonvulsant drugs and hematological disease.

Many antiepileptic drugs (AEDs) are associated with hematological disorders that range from mild thrombocytopenia or neutropenia to anemia, red cell aplasia, until bone marrow failure. Fortunately, potentially fatal hematological disorders such as aplastic anemia are very rare. This review investigates hematological effects associated with classic and newer AEDs: a PubMed search indexed for MEDLINE was undertaken to identify studies in adults, children and animals using the name of all anticonvulsant drugs combined with the terms "hematological disease" and "hematological abnormalities" as key words. The most common hematological alterations occur with older AEDs than newer. Indeed, careful hematological monitoring is needed especially using carbamazepine, phenytoin and valproic acid. The pathogenetic mechanisms are still unknown: they seem to be related to an immunological mechanism, but drugs pharmacokinetics and pharmacodynamics interactions may also play an important role. Further research is needed to assess the real pathogenetic mechanism at the basis of hematological complications caused by AEDs.

Introducing the GRACEnet/REAP Data Contribution, Discovery, and Retrieval System.

Difficulties in accessing high-quality data on trace gas fluxes and performance of bioenergy/bioproduct feedstocks limit the ability of researchers and others to address environmental impacts of agriculture and the potential to produce feedstocks. To address those needs, the GRACEnet (Greenhouse gas Reduction through Agricultural Carbon Enhancement network) and REAP (Renewable Energy Assessment Project) research programs were initiated by the USDA Agricultural Research Service (ARS). A major product of these programs is the creation of a database with greenhouse gas fluxes, soil carbon stocks, biomass yield, nutrient, and energy characteristics, and input data for modeling cropped and grazed systems. The data include site descriptors (e.g., weather, soil class, spatial attributes), experimental design (e.g., factors manipulated, measurements performed, plot layouts), management information (e.g., planting and harvesting schedules, fertilizer types and amounts, biomass harvested, grazing intensity), and measurements (e.g., soil C and N stocks, plant biomass amount and chemical composition). To promote standardization of data and ensure that experiments were fully described, sampling protocols and a spreadsheet-based data-entry template were developed. Data were first uploaded to a temporary database for checking and then were uploaded to the central database. A Web-accessible application allows for registered users to query and download data including measurement protocols. Separate portals have been provided for each project (GRACEnet and REAP) at nrrc.ars.usda.gov/slgracenet/#/Home and nrrc.ars.usda.gov/slreap/#/Home. The database architecture and data entry template have proven flexible and robust for describing a wide range of field experiments and thus appear suitable for other natural resource research projects.

Rufinamide in refractory childhood epileptic encephalopathies other than Lennox-Gastaut syndrome.

BACKGROUND: To report on the first multicenter Italian experience with rufinamide as adjunctive drug in children, adolescents and young adults with refractory childhood-onset epileptic encephalopathies other than Lennox-Gastaut syndrome. METHODS: Thirty-eight patients (19 males, 19 females), aged between 4 and 34 (mean 13.7 ± 8.3, median 12.5), all affected by different types of childhood-onset refractory epileptic encephalopathies other than Lennox-Gastaut syndrome, were treated with rufinamide as adjunctive drug for a mean period of 11.4 months (range 3-26 months). RESULTS: Fifteen of 38 patients (39.5%) had a ≥ 50% seizure reduction in countable seizures. Complete seizure freedom was achieved in one of these patients (2.6%). Three patients (7.9%) had a 25-49% seizure reduction, whilst seizure frequency remained unchanged in 15 (39.5%) and increased in five patients (13.1%). Eleven patients (28.9%) reported adverse side effects. Vomiting was reported in five patients (13.1%); drowsiness, decreased appetite and irritability with migraine manifested in other four patients. They were transient and mild in all cases. CONCLUSION: Rufinamide may be an effective and well-tolerated adjunctive drug for the treatment of refractory childhood-onset epileptic encephalopathies other than Lennox-Gastaut syndrome. Rufinamide was most effective in patients with drop-attacks and (bi)frontal spike-wave discharges.

Brenneria salicis Associated with Watermark Disease Symptoms on Salix alba in Italy.

From 1999 to 2010, withering of white willow was observed on trees growing along roads or irrigation canals in Torino, Alessandria, and Vercelli provinces of Italy, with incidence varying from 15, 25, and 30%, respectively. In spring and autumn 2008, six samples from withering branches with bark cankers were collected. On the bark surface near the cankers, iridescent traces of dried ooze were found. Tissues immediately below the cankers were dark with water-soaked, olive-colored edges. In some cases, the xylem appeared affected. Small fragments taken from the affected tissue on both edges of bark alterations and darkened vessels were crushed into mortars with sterile saline. Ten-fold serial dilutions (10-1, 10-2) were also performed. Aliquots of 0.1 ml were plated on nutrient agar and incubated at 25°C for 4 days. Bacterial colonies were ivory to white, circular, and bright, with a diameter of ~2 mm. Isolates were negative for Gram staining, presence of arginine dehydrolase, oxidase, phenylalanine deaminase, urease, hydrolysis of gelatin and starch, nitrate reduction, acidity from d-arabinose, cellobiose, lactose, maltose, trehalose, xylose, and pectinolytic activity on potato slices; positive for the presence of catalase and levan, fermentative metabolism of glucose, acid production from aesculin, l-arabinose, dextrose, d-galactose, inositol, d-mannitol, α-methylglucoside, raffinose, salicin and sucrose, H2S production from cysteine, and bright yellow pigment production on autoclaved potato tissue. They were not fluorescent on King's medium B and did not induce hypersensitivity reaction on tobacco leaf. Similar results were obtained with Brenneria salicis control strain, LMG 6089, except for acid production from α-methylglucoside (negative) and l-arabinose (negative). Acid production from α-methylglucoside has been reported for the Japanese strains of B. salicis, which do not produce acidity from inositol (4). Genomic DNA was extracted (1) from three isolates, and PCR reactions were performed with Es1A and Es4B primers (2) that amplify a 553-bp fragment from the 16S rDNA of B. salicis. The isolates showed a PCR product of expected size, like the positive control LMB 6089. On the basis of colony features, biochemical tests, and the PCR assay, we conclude that the isolates belong to B. salicis, a pathogen reported in Belgium, Germany, Great Britain, the Netherlands, Hungary, Japan, and New Zealand (2,3) but, as well as watermark disease symptoms, never previously reported in Italy. In summer 2009, pathogenicity tests were performed by inoculating young, white willow plants with B. salicis suspensions of ~1 to 2 × 109 CFU/ml placed with a syringe at the intersection of 1-year-old branches on the trunk. However, a year later, no symptoms of disease have been noted on the inoculated plants. According to the literature, pathogenicity tests rarely lead to the expected results because the bacterium can survive for many years in latent form, breaking out only when proper environmental conditions occur (3). Also the tests with B. salicis LMG 6089 gave negative results. Further investigation is necessary to clarify the relationships between this bacterium and the environment in causing withering of white willows in Piedmont. References: (1) W. P. Chen and T. T. Kuo. Nucleic Acids Res. 21:2260, 1993. (2) L. Hauben et al. Appl. Environ. Microbiol. 64:3966, 1998. (3) M. Maes et al. Environ. Microbiol. 11:1453, 2009. (4) Y. Sakamoto et al. Plant Pathol. 48:613, 1999.

SARS-CoV-2 mRNA vaccine BNT162b2 triggers a consistent cross-variant humoral and cellular response.

As the SARS-CoV-2 pandemic continues to rage worldwide, the emergence of numerous variants of concern (VOC) represents a challenge for the vaccinal protective efficacy and the reliability of commercially available high-throughput immunoassays. Our study demonstrates the administration of two doses of the BNT162b2 vaccine that elicited a robust SARS-CoV-2-specific immune response which was assessed up to 3 months after full vaccination in a cohort of 37 health care workers (HCWs). SARS-CoV-2-specific antibody response, evaluated by four commercially available chemiluminescence immunoassays (CLIA), was qualitatively consistent with the results provided by the gold-standard in vitro neutralization assay (NTA). However, we could not observe a correlation between the quantity of the antibody detected by CLIA assays and their neutralizing activity tested by NTA. Almost all subjects developed a SARS-CoV-2-specific T-cell response. Moreover, vaccinated HCWs developed a similar protective neutralizing antibodies response against the EU (B.1), Alpha (B.1.1.7), Gamma (P.1), and Eta (B.1.525) SARS-CoV-2 variants, while Beta (B.1.351) and Delta (B.1.617.2) strains displayed a consistent partial immune evasion. These results underline the importance of a solid vaccine-elicited immune response and a robust antibody titre. We believe that these relevant results should be taken into consideration in the definition of future vaccinal strategies.

Levetiracetam monotherapy for childhood occipital epilepsy of gastaut.

OBJECTIVES: The aim of this open label pilot study was to evaluate the efficacy and tolerability of levetiracetam (LEV) as 'de novo' monotherapy in children and adolescents with late onset childhood occipital epilepsy-Gastaut type (COE-G). MATERIAL AND METHODS: Twelve patients suffering from COE-G were enrolled in this prospective study. The age of seizures onset ranged from 6.1 to 16.2 years with a peak of frequency at mean (+/-SD) 10.54 +/- 2.77 years. Therapy with LEV was started at 10 mg/kg/day and, after titration, the final dose was generally achieved within 4 weeks and ranged from 20.7 to 45.2 mg/kg/day. RESULTS: At the 6 month evaluation, 11 (91.6%) of the 12 patients studied were seizure free, and one (8.3%) showed four additional episodes. Electroencephalography (EEG) activity was normal in six (54.5%) patients, unchanged in two (18.1%) children, and in four (33.3%) patients sporadic occipital abnormalities persisted. At the 12-month evaluation all patients were completely seizure free. Four patients (33.3%) continued to show some EEG abnormalities, while eight (72.8%) patients had normal EEG. At the 18-month evaluation all patients were seizure free and 10 patients (83.3%) showed a complete normalization of EEG abnormalities. DISCUSSION: Monotherapy with LEV was effective and well tolerated in patients with COE-G. Nevertheless, prospective, large, long-term double-blind studies are needed to confirm these findings.

Apoptosis and erythroid differentiation triggered by Bcr-Abl inhibitors in CML cell lines are fully distinguishable processes that exhibit different sensitivity to caspase inhibition.

Imatinib targets the Bcr-Abl oncogene that causes chronic myelogenous leukemia (CML) in humans. Recently, we demonstrated that besides triggering apoptosis in K562 cells, imatinib also mediated their erythroid differentiation. Although both events appear to proceed concomitantly, it is not known at present whether or not imatinib-induced apoptosis and differentiation are interdependent processes. Hence, we investigated the requirements for Bcr-Abl inhibitor-mediated apoptosis and erythroid differentiation in several established and engineered CML cell lines. Imatinib triggered apoptosis and erythroid differentiation of different CML cell lines, but only apoptosis exhibited sensitivity to ZVAD-fmk inhibition. Conversely, the p38 mitogen-activated protein (MAP) kinase inhibitor, SB202190, significantly slowed down erythroid differentiation without affecting caspase activation. Furthermore, imatinib and PD166326, another Bcr-Abl inhibitory molecule, triggered erythroid differentiation of K562 cell clones, nevertheless resistant to Bcr-Abl inhibitor-induced apoptosis. Finally, short hairpin RNA inhibitor (shRNAi) silencing of caspase 3 efficiently inhibited caspase activity but had no effect on erythroid differentiation, whereas silencing of Bcr-Abl mimicked imatinib or PD166326 treatment, leading to increased apoptosis and erythroid differentiation of K562 cells. Taken together, our findings not only demonstrate that Bcr-Abl inhibitor-mediated apoptosis and differentiation are fully distinguishable events, but also that caspases are dispensable for erythroid differentiation of established CML cell lines.

Efficacy and safety of felbamate in children under 4 years of age: a retrospective chart review.

BACKGROUND AND PURPOSE: To review our experience of the efficacy and tolerability of felbamate in children younger than 4 years. METHODS: We used a retrospective chart review to identify 53 children with seizures who were younger than 4 years. Efficacy was evaluated based on the occurrence of responsiveness, defined as seizure frequency reduction of more than 50% for a minimum period of 4 months. Tolerability was based on parent-reported side effects. RESULTS: Twenty-two (41%) patients resulted to be responders and 31 (59%) did not. By univariate analysis, those achieving seizure remission were probably much older, to have a shorter history of epilepsy and a lower frequency of seizures before felbamate therapy. The number of antiepileptic drugs (AEDs) used before felbamate therapy was the only significant predictor of the duration of response to felbamate, with a longer responsiveness to the drug seen in those who were placed under fewer than three AEDs before felbamate compared with those who had taken more than three (median, 16 months vs. 7 months; P < 0.0084). Side effects occurred in 30% of the subjects, but these did not require discontinuation of the drug. DISCUSSION: Felbamate is an effective medication for a wide range of epilepsy syndromes in children younger than 4 years. Although caution is necessary when the drug is used in children, felbamate might represent a possible option for the treatment of epilepsy in this age group.

CagA and VacA Helicobacter pylori antibodies in gastric cancer.

BACKGROUND: Infection with different genotypes of virulent Helicobacter pylori strains (cytotoxin-associated gene A [CagA]- and/or vacuolating cytotoxin A [VacA]-positive) can play a role in the development of atrophic gastritis, duodenal ulcer (DU) and gastric cancer (GC). OBJECTIVE: To determine whether patients with GC and H pylori-negative histological staining had previously been infected with H pylori CagA- and/or VacA-positive virulent strains. METHODS: Twenty-three GC patients with a mean (+/- SD) age of 68.14+/-9.8 years who tested H pylori-negative on histological staining took part in the study. Three control groups were included. The first group comprised 19 patients with past H pylori infection and DUs eradicated 10 years earlier, with a mean age of 58+/-18.2 years. H pylori-negative status for this group was determined every year with Giemsa staining, and follow-up testing occured 120+/-32 months (mean +/- SD) after therapy. The subsequent control groups included 20 asymptomatic children, with a mean age of 7+/-4.47 years, and with H pylori-negative fecal tests; the final group contained 30 patients without clinical symptoms of H pylori infection, with a mean age of 68+/-11.6 years, who tested H pylori-negative by histological staining. RESULTS: Prevalence of CagA and VacA seropositivity, respectively was 82.6% and 73.91% in GC patients; 84.2% and 84.2% in H pylori-negative DU patients; 25% and 5% in H pylori-negative children; and 36.6% and 16.6% in the patients without clinical symptoms on histological staining. CagA and VacA antibody positivity was not significantly different between GC patients and patients with DUs that had been eradicated 10 years earlier. Significant positivity was found between the children's group and the H pylori-negative (with past DUs) group (P<0.001). A statistically significant difference was found in age between groups (P<0.03). CONCLUSIONS: Patients with GC, even when H pylori-negative at the time of the present study, may have been infected by H pylori before the onset of the disease, as confirmed by CagA and VacA seropositivity. These data reinforce the hypothesis that H pylori may be a direct carcinogenic agent of GC.

Testing DAYCENT model simulations of corn yields and nitrous oxide emissions in irrigated tillage systems in Colorado.

Agricultural soils are responsible for the majority of nitrous oxide (N(2)O) emissions in the USA. Irrigated cropping, particularly in the western USA, is an important source of N(2)O emissions. However, the impacts of tillage intensity and N fertilizer amount and type have not been extensively studied for irrigated systems. The DAYCENT biogeochemical model was tested using N(2)O, crop yield, soil N and C, and other data collected from irrigated cropping systems in northeastern Colorado during 2002 to 2006. DAYCENT uses daily weather, soil texture, and land management information to simulate C and N fluxes between the atmosphere, soil, and vegetation. The model properly represented the impacts of tillage intensity and N fertilizer amount on crop yields, soil organic C (SOC), and soil water content. DAYCENT N(2)O emissions matched the measured data in that simulated emissions increased as N fertilization rates increased and emissions from no-till (NT) tended to be lower on average than conventional-till (CT). However, the model overestimated N(2)O emissions. Lowering the amount of N(2)O emitted per unit of N nitrified from 2 to 1% helped improve model fit but the treatments receiving no N fertilizer were still overestimated by more than a factor of 2. Both the model and measurements showed that soil NO(3)(-) levels increase with N fertilizer addition and with tillage intensity, but DAYCENT underestimated NO(3)(-) levels, particularly for the treatments receiving no N fertilizer. We suggest that DAYCENT could be improved by reducing the background nitrification rate and by accounting for the impact of changes in microbial community structure on denitrification rates.

2q24-q31 deletion: report of a case and review of the literature.

We report a patient with a de novo interstitial deletion of the long arm of chromosome 2 involving bands 2q24.3-q31.1. The patient shows postnatal growth retardation, microcephaly, ptosis, down-slanting palpebral fissures, long eyelashes and micrognathia. Halluces are long, broad and medially deviated, while the other toes are laterally deviated and remarkably short with hypoplastic phalanges. She also showed developmental delay, seizures, lack of eye contact, stereotypic and repetitive hand movements and sleep disturbances with breath holding. Prenatal and three independent postnatal karyotypes were normal. Array-CGH analysis allowed us to identify and characterize a "de novo" 2q interstitial deletion of about 10.4Mb, involving segment between cytogenetic bands 2q24.3 and 2q31.1. The deletion was confirmed by quantitative PCR. About 30 children with 2q interstitial deletion have been reported. The deletion described here is overlapping with 15 of these cases. We have attempted to compare the clinical features of our patient with 15 overlapping cases. The emerging phenotypes include low birth weight, postnatal growth retardation, mental retardation and developmental delay, microcephaly, and peculiar facial dysmorphisms. Peculiar long and broad halluces with an increased distance between the first and the second toe are ("sandal gap" sign) present in most of the described patients. The gene content analysis of the deleted region revealed the presence of some genes that may be indicated as good candidates in generating both neurological and dysmorphic phenotype in the patient. In particular, a cluster of SCNA genes is located within the deleted region and it is known that loss of function mutations in SCNA1 gene cause a severe form of epilepsy.