CHI3L1 and CHI3L2 overexpression in motor cortex and spinal cord of sALS patients.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by the degeneration and death of upper (UMN) and lower (LMN) motor neurons. In the last decade, it has been shown that Chitinases are an important prognostic indicator of neuro-inflammatory damage induced by microglia and astrocytes. MATERIALS AND METHODS: We analyzed microarray datasets obtained from the Array Express in order to verify the expression levels of CHI3L1 and CHI3L2 in motor cortex biopsies of sALS patients with different survival times. We also divided the sALS patients into smokers and non-smokers. In order to extend our analysis, we explored two additional microarray datasets, GSE833 and GSE26927, of post-mortem spinal cord biopsies from sALS patients. RESULTS: The analysis showed that CHI3L1 and CHI3L2 expression levels were significantly upregulated in the motor cortex of sALS patients, compared to the healthy controls. Moreover, their expression levels were negatively correlated with survival time. Interesting results were obtained when we compared the expression levels of Chitinases among smokers. We showed that CHI3L1 and CHI3L2 were significantly upregulated in sALS smokers compared to non-smokers. Furthermore, we found that four genes belonging to the Chitinases network (SERPINA3, C1s, RRAD, HLA-DQA1) were significantly upregulated in the motor cortex of sALS patients and positively correlated with Chitinases expression levels. Similar results were obtained during the exploration of the two-microarray dataset. CONCLUSIONS: This study suggests that CHI3L1 and CHI3L2 are associated with the progression of neurodegeneration in motor cortex and spinal cord of sALS patients.

Pollen-pistil interactions and early fruiting in parthenocarpic citrus.

BACKGROUND AND AIMS: An intense pollen-pistil interaction precedes fertilization. This interaction is of particular relevance in agronomically important species where seeds or fruits are the edible part. Over time some agronomically species have been selected for the ability to produce fruit without seeds. While this phenomenon is critical for commercial production in some species, very little is known about the events behind the production of seedless fruit. In this work, the relationship between pollen-pistil interaction and the onset of fruiting was investigated in citrus mandarin. METHODS: Pistils were sequentially examined in hand-pollinated flowers paying attention to pollen-tube behaviour, and to cytochemical changes along the pollen-tube pathway. To evaluate which of these changes were induced by pollination/fertilization and which were developmentally regulated, pollinated and unpollinated pistils were compared. Also the onset of fruiting was timed and changes in the ovary examined. KEY RESULTS: Conspicuous changes occurred in the pistil along the pollen-tube pathway, which took place in a basipetal way encompassing the timing of pollen-tube growth. However, these changes appear to be developmentally regulated as they happened in the same way and at the same time in unpollinated flowers. Moreover, the onset of fruiting occurred prior to fertilization and the very same changes could be observed in unpollinated flowers. CONCLUSIONS: Pollen-pistil interaction in citrus showed similarities with unrelated species and families belonging to other taxa. The uncoupling of the reproductive and fruiting processes accounts for the parthenocarpic ability of unpollinated flowers to produce fruit in citrus. However, the maintenance of a functional reproductive process reflects the potential to produce seeded fruits, providing a basis for the understanding of the production of seeded or unseeded fruits and further understanding of the process of parthenocarpy in other species.

Genetic characterization of an almond germplasm collection and volatilome profiling of raw and roasted kernels.

Almond is appreciated for its nutraceutical value and for the aromatic profile of the kernels. In this work, an almond collection composed of 96 Sicilian accessions complemented with 10 widely cultivated cultivars was phenotyped for the production of volatile organic compounds using a proton-transfer time-of-flight mass spectrometer and genotyped using the Illumina Infinium®18 K Peach SNP array. The profiling of the aroma was carried out on fresh and roasted kernels enabling the detection of 150 mass peaks. Sixty eight, for the most related with sulfur compounds, furan containing compounds, and aldehydes formed by Strecker degradation, significantly increased during roasting, while the concentration of fifty-four mass peaks, for the most belonging to alcohols and terpenes, significantly decreased. Four hundred and seventy-one robust SNPs were selected and employed for population genetic studies. Structure analysis detected three subpopulations with the Sicilian accessions characterized by a different genetic stratification compared to those collected in Apulia (South Italy) and the International cultivars. The linkage-disequilibrium (LD) decay across the genome was equal to r2 = 0.083. Furthermore, a high level of collinearity (r2 = 0.96) between almond and peach was registered confirming the high synteny between the two genomes. A preliminary application of a genome-wide association analysis allowed the detection of significant marker-trait associations for 31 fresh and 33 roasted almond mass peaks respectively. An accurate genetic and phenotypic characterization of novel germplasm can represent a valuable tool for the set-up of marker-assisted selection of novel cultivars with an enhanced aromatic profile.

A case of isolated pachygyria with unusual clinical onset in the neonatal period.

Pachygyria is a malformation of the cerebral cortex characterized by an insufficient development of the gyri and cerebral sulci within the anomalies of neuronal migration. Clinically, can cause seizures, mental retardation and motor deficits. We report a rare clinical case of pachygyria in a newborn with persistent hypotonia and sub-clinical seizures in which early diagnosis was possible thanks to cranial magnetic resonance imaging.

Temperatures during flower bud development affect pollen germination, self-incompatibility reaction and early fruit development of clementine (Citrus clementina Hort. ex Tan.).

One of the key environmental factors affecting plant reproductive systems is temperature. Characterising such effects is especially relevant for some commercially important genera such as Citrus. In this genus, failure of fertilisation results in parthenocarpic fruit development and seedlessness, which is a much-prized character. Here, we characterise the effects of temperature on flower and ovary development, and on pollen-pistil interactions in 'Comune' clementine (Citrus clementina Hort. ex Tan.). We examine flower bud development, in vitro pollen germination and pollen-pistil interaction at different temperatures (15, 20, 25 or 30 °C). These temperatures span the range from 'cold' to 'hot' weather during the flowering season in many citrus-growing regions. Temperature had a strong effect on flower and ovary development, pollen germination, and pollen tube growth kinetics. In particular, parthenocarpic fruit development (indicated by juice vesicle growth) was initiated early if flowers were exposed to warmer temperatures during anthesis. Exposure to different temperatures during flower bud development also alters expression of the self-incompatibility reaction. This affects the point in the pistil at which pollen tube growth is arrested and confirms the role of sub- and supra-optimal temperatures in determining the numbers of pollen tubes reaching the ovary.

Induction of OAS gene family in HIV monocyte infected patients with high and low viral load.

BACKGROUND: The innate immunity plays a predominant role in the early control of HIV infection, before the induction of adaptive immune responses. The cytokine secretion operated by the CD4(+) T helper cells is able to induce a response in the innate immunity cells and significantly affect HIV-1 persistence and replication. One of the pathways activated by monocytes to restrain viral infection is the 2' -5' -oligoadenylate synthetase (OAS)/RNase L pathway. OAS is activated by dsRNA and IFNs to produce 2' -5' oligoadenylates, which are activators of RNase L. This enzyme degrades viral and cellular RNAs, thus restricting viral infection. MATERIALS AND METHODS: We analyzed a microarray dataset obtained from the NCBI Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) databank (accession number GSE18464) in order to verify the modulation of the OAS gene family in CD14 (+) monocytes isolated from 55 subjects, 22 with HIV-1 HVL (high viral load), and 22 with HIV-1 LVL (low viral load), as well as in 11 HIV-1 seronegative controls. We have validated the data on the expression levels of the OAS genes by performing real-time PCR on monocyte from a cohort of HIV infected patients (n = 20), with clinical characteristics similar to those of the patients recruited in the study present in the microarray. RESULTS: Microarray analysis showed that OAS gene family are significantly upregulated in monocyte of HIV-1 patients with HVL, as compared to LVL patients and to healthy donors. Furthermore, we showed a significant correlation between the OAS gene family and the log2 viral load and CD4 count. These results were confirmed by the in vitro validation. CONCLUSIONS: Data from this study suggest an involvement for the OAS gene family in the control of HIV-1 infection.

A new Chinese hamster ovary cell line expressing alpha2,6-sialyltransferase used as universal host for the production of human-like sialylated recombinant glycoproteins.

Chinese hamster ovary (CHO) cells are widely employed to produce glycosylated recombinant proteins. Our group as well as others have demonstrated that the sialylation defect of CHO cells can be corrected by transfecting the alpha2,6-sialyltransferase (alpha2,6-ST) cDNA. Glycoproteins produced by such CHO cells display both alpha2,6- and alpha2,3-linked terminal sialic acid residues, similar to human glycoproteins. Here, we have established a CHO cell line stably expressing alpha2,6-ST, providing a universal host for further transfections of human genes. Several relevant parameters of the universal host cell line were studied, demonstrating that the alpha2,6-ST transgene was stably integrated into the CHO cell genome, that transgene expression was stable in the absence of selective pressure, that the recombinant sialyltransferase was correctly localized in the Golgi and, finally, that the bioreactor growth parameters of the universal host were comparable to those of the parental cell line. A second step consisted in the stable transfection into the universal host of cDNAs for human glycoproteins of therapeutic interest, i.e. interferon-gamma and the tissue inhibitor of metalloproteinases-1. Interferon-gamma purified from the universal host carried 40.4% alpha2,6- and 59.6% alpha2,3-sialic acid residues and showed improved pharmacokinetics in clearance studies when compared to interferon-gamma produced by normal CHO cells.

Effect of glucose priming on insulin response in the premature infant.

Our paper deals with premature infants in the first twenty-four hours of life and reports the effect of a preinfusion of glucose on glucose administration. Glucose infusion (2.5 gm.) resulted in a slight elevation of serum insulin. When this administration of glucose was preceded by a two-hour infusion of glucose, there was a striking increase in serum insulin.

Effect of priming of amino acids on insulin and growth hormone response in the premature infant.

Glucose, alpha-amino nitrogen, serum insulin, and HGH were studied in preterm infants during the first 24 hours of life. Glucose infusion (1.25 gm.) resulted in a slight elevation of serum insulin. When this amount of glucose was infused during the last 30 minutes of a two-and-a-half-hour infusion of a mixture of essential amino acids, there was a rapid and striking increase in serum insulin. However, this increase was not associated with a faster glucose disposal rate. The administration of this mixture of amino acids doubled the basal level of alpha-amino nitrogen, and during the first two hours, before glucose infusion, it caused a significant rise of serum insulin and HGH. In both cases glucose caused an increase of HGH secretion that was not significantly different in the two groups of infants.

Presenting symptoms and signs after whiplash injury: the influence of accident mechanisms.

OBJECTIVE: To assess the relationship between accident mechanisms and initial findings after whiplash injury. DESIGN: Cohort study. SETTING: Outpatient department, Department of Neurology, University of Berne, Switzerland. PATIENTS: A population-based sample of 137 consecutive patients referred by primary care physicians. Fractures or dislocations of the cervical spine, head trauma, and preexisting neurologic disorders were exclusion criteria. MAIN OUTCOME MEASURES: Patients were interviewed and examined within 7.2 days (SD, 3.9 days) after trauma. Analyzed accident features were position in the car, use of seat belt, head restraint and its point of head contact, damage to seat, head position and state of preparedness at the moment of impact, and type of collision. Analyzed symptoms were intensity and onset delay of post-traumatic head and neck pain; pain in the shoulders, back, and anterior neck; symptoms of neurologic dysfunction according to presumed origin--cranial nerve or brainstem, radicular or myelopathic; and a score of multiple symptoms. Analyzed signs were neck muscle tenderness and restricted neck movement, and signs of cranial nerve, brainstem, or radicular dysfunction. RESULTS: Passenger position in the car, use of seat belt, and the presence of a head restraint showed no significant relationship with findings. Rotated or inclined head position at the moment of impact was associated with a higher frequency of multiple symptoms (p = 0.045 and 0.008) with more severe symptoms and signs of musculoligamental cervical strain (p = 0.048 and 0.038) and of neural, particularly radicular (p = 0.031 and 0.019), damage. Unprepared occupants had a higher frequency of multiple symptoms (p = 0.031) and more severe headache (p = 0.046). Rear-end collision was associated with a higher frequency of multiple symptoms (p = 0.006), especially of cranial nerve or brainstem dysfunction (p = 0.00003). CONCLUSION: Three features of accident mechanisms were associated with more severe symptoms: an unprepared occupant; rear-end collision, with or without subsequent frontal impact; and rotated or inclined head position at the moment of impact.

Dextrocardia with and without situs viscerum inversus in two sibs.

We described two sibs born to consanguineous Sicilian parents who died of severe congenital heart malformation. Both had dextrocardia; however, only the girl had situs viscerum inversus. At necropsy she was found to have a right spleen and right pulmonary isomerism (three lobes in each lung, as commonly found in the asplenia syndrome). This observation, together with other literature reports, suggest that isolated dextrocardia, situs viscerum inversus, and the asplenia-polysplenia complex may be different end results of a unique dysmorphogenetic process involving the embryonic midline.

Evaluation of transdermal theophylline pharmacokinetics in neonates.

Theophylline may be administered by several routes, but problems are associated with neonatal dosing. The transdermal route may provide a safer and noninvasive method of administration, yet produce therapeutic concentrations in a consistent and reliable manner. To study the feasibility of this in the apnea of prematurity, stable neonates were administered a subtherapeutic transdermal dose for 24 hours in order to assess pharmacokinetics and bioavailability. This was followed with routine intravenous theophylline therapy according to institutional policy. Six of nine neonates had detectable serum theophylline concentrations that increased slowly after patch application. Mean (+/- SD) maximum serum concentration was 2.4 +/- 1.3 micrograms/ml, mean time to maximum serum concentration was 22 +/- 8.2 hours, and mean latency period was 8.0 +/- 4.9 hours. Mean total amount of theophylline delivered to the skin was 18.6 +/- 4.1 mg. Mean fractional absorption at 30 hours was 0.25 +/- 0.12. These data demonstrate that it is possible to produce systemic theophylline concentrations with a transdermal patch in preterm infants sufficient to study pharmacokinetics and bioavailability, and that transdermal delivery of therapeutic doses is technologically feasible.

Management of chronic subdural hematoma in patients treated with anticoagulation.

BACKGROUND: The diffusion of the surgical technique of cardiac valve replacement with metallic prostheses, as well as bypass graft in the arterial occlusive disease of the lower extremities, both requiring permanent oral anticoagulation, has increased the number of patients affected by chronic subdural hematoma that can be diagnosed at an earlier stage of this disease with the advent of the CT. METHODS: The records of seven patients with mean GCS = 14.2 and mean clinical grade = 1.85 affected by chronic subdural hematoma and in treatment with anticoagulants were examined retrospectively. All the patients underwent subtemporal craniectomy plus closed drainage or burrhole(s) plus closed drainage after immediate correction of hypocoagulability by administration of vitamin K and fresh frozen plasma and normalization of PA by calcium heparin. RESULTS: Outcome was good for all the patients except one who died because of cerebral herniation due to massive solid subdural hematoma during extracorporeal dialysis. Complications included: intracerebral hemorrhage, solid subdural hematoma, slow brain reexpansion, subdural collection reaccumulation and cerebral embolism. Three patients required re-operation. Mean duration of hospital stay was 18 days with range from 7 to 24 days. CONCLUSIONS: Basing on this retrospective study and the proposed pathophysiology, the guidelines for optimal management of this subgroup of patients are proposed. Recommendations include the immediate correction of hypocoagulability, the appropriate surgical technique and the cautious conversion to oral anticoagulation as well as the appropriate timing of such conversion.

Traumatic chronic subdural hematoma over 80 years. A preliminary prospective study.

Six very elderly patients (mean of age: 85 years with range from 80 to 95 years) with mean GCS = 12 and mean clinical grade = 2.5 affected by traumatic chronic subdural hematoma (CT mean maximum thickness = 2.8 +/- 0.46 cm with midline shift = 1.56 +/- 0.48 cm and absence of homolateral mesencefalic cistern in all case but one) underwent parietal or frontal craniectomy under temporalis muscle and 48-h closed subdural drain. There was no mortality as consequence of the operative procedure. In all the patients but one who died postoperatively from a preoperative midbrain infarction secondary to a transtentorial herniation, there was a progressive and slow clinical improvement in spite of residual markedly persistent fluid collection (CT mean maximum thickness 1.44 +/- 0.19 cm) with mass effect (CT mean midline shift = 0.5 +/- 0.17 cm) due to a some failure of the brain to re-expand. Impairment of hemodynamic reserve should be considered as important cause of failure of the brain re-expansion. Clinical and CT control within two months after discharge from hospital demonstrated further clinical improvement (mean GOS = 4.6) and resolution of subdural residual fluid collection. Basing on these results we recommend do not reoperate persistent subdural fluid collection if there is clinical improvement. The patient can be discharged from hospital or transferred to Geriatric Department where he can be clinically and CT evaluated. Only a clinical deterioration or an increase of residual subdural fluid collection provides clear indication to reoperative surgery.

[Characteristic aspects of the therapy of heart failure in infancy. Review of the literature and personal data]. / Aspetti peculiari della terapia dello scompenso cardiaco nell'infanzia. Revisione della letteratura e dati personali.

The treatment of congestive heart failure in view of its pathophysiology can be divided in 3 parts: cardiokinetic therapy, diuretic therapy and vasodilator therapy. For each therapeutic component we report the latest findings and underline the peculiar aspects in the newborn. Furthermore we outline the basis for a rational use of the various types of drugs and indicate the future therapeutic prospectives.

[Cardiac involvement in tuberous sclerosis in the first months of life: physiopathologic and clinical aspects of cardiac rhabdomyoma]. / Il coinvolgimento cardiaco nella sclerosi tuberosa nei primi mesi di vita: aspetti fisiopatologici e clinici dei rabdomiomi cardiaci.

Cardiac rhabdomyomas are frequent in association with tuberous sclerosis and they are the first symptoms of Bourneville disease in fetal and neonatal period. Clinical findings of cardiac rhabdomiomas are quite heterogeneous: asymptomatic, cardiac murmur, cardiomegaly, heart failure or arrhythmias. Echocardiography can determine site, dimensions, numbers and haemodynamic consequences of cardiac tumours and their clinical evolution at follow-up. In this study the Authors report clinical findings in 9 cases of cardiac rhabdomyomas in newborn infants: 3 has familiarity for tuberous sclerosis and two of these had prenatal echocardiographic diagnosis; in the other 6 cases diagnosis was casual (1 in fetal period). All patients with prenatal diagnosis were asymptomatic. In other cases 1 had extrasystolic arrhythmias and five had only cardiac murmurs. Echocardiographic follow-up (6 months to 5 years) showed regression of number and dimension of cardiac masses in all cases. In 7 cases cardiac rhabdomiomas were associated with tuberous sclerosis.

[Double phototherapy with Wallaby optic fibers versus conventional phototherapy. Case reports]. / Fototerapia doppia con fibre ottiche Wallaby versus fototerapia convenzionale. Contributo casistico.

The authors have valued the efficacy of the double phototherapy with fiberoptic Wallaby vs conventional phototherapy in 2 groups of term infants, without any complication at birth, utilized respectively as study group and control group. While conventional phototherapy produced a bilirubin reduction of 0.60 +/- 0.26% per hour (with a total reduction of 28.1 +/- 11.1%), the double phototherapy was statistically more effective (p < 0.05) then conventional phototherapy causing a bilirubin reduction of 0.73 +/- 0.28% (with a total reduction of 33.3 +/- 9.5%). At 24 hour after the interruption of the treatment 9 newborns of the study group (36%) and 7 of the control group (28%) presented a rebound effect (increase of the bilirubinemia more than 17 mumol/l), but without a statistical difference (p > 0.05). Our study shows that double phototherapy with Wallaby fiberoptic and conventional phototherapy represent a valid strategy in the treatment of the non haemolytic neonatal hyperbilirubinemia, because, compared to conventional phototherapy, double phototherapy is more effective and reduces the period of the treatment, showing a simple management of the jaundiced newborn.

[Kawasaki disease in Sicily: description of the first case with giant coronary aneurysm]. / La malattia di Kawasaki in Sicilia: descrizione del primo caso con aneurisma gigante delle coronarie.

A case of Kawasaki disease with early development of giant coronary artery aneurysm is reported. The delay in the diagnosis and consequently in the use of correct therapy has conditioned the outcome of the illness. We don't know the predictive factors of cardiac complications, but steroid treatment in our patient probably had an important role in the cardiac damage. The use of echocardiography in the evaluation of coronary aneurysm has confirmed the sensitivity, specificity and predictive value of this technique in detecting cardiac lesions.

[Physiopathologic and therapeutic aspects of persistent fetal circulation. Review of the literature and personal histological observations]. / Aspetti fisiopatologici e terapeutici della persistenza della circolazione fetale. Revisione della letteratura ed osservazioni istologiche personali.

Persistence of the fetal circulation (PFC) is a syndrome characterized by failure of the cardiocirculatory system to adapt successfully to postnatal life. Its typical feature is persisting right-left shunt across fetal channels which determines cyanosis refractory to oxygen treatment. PFC can simulate cyanotic congenital cardiopathy. It has two forms: a primitive form and secondary one due to various causes especially perinatal asphyxia. Both forms have a common pathogenesis consisting of hypertension of the pulmonary arterial circulation. This article reviews the physiology of the main prenatal and postnatal circulatory characteristics and the factors which regulate the pulmonary circulation. It also reports the latest findings on PFC physiopathology and treatment indicating the prognostic factors and future perspectives.

[CHARGE association: report of a clinical case with anal atresia and rectovaginal fistula]. / Associazione CHARGE: descrizione di un caso clinico con atresia anale e fistola retto-vaginale.

CHARGE association is a non-random constellation of Coloboma, Heart Disease, Atresia of the choana, Retarded mental development and growth, Genital hypoplasia, Ear anomalies and deafness. We report on a newborn with CHARGE association. In addition to the typical features our case presented anal atresia and rectovaginal fistula. Our patient had congenital cardiopathy and feeding problems and died at the age of 3 months. Most case of CHARGE association appear to have a primary defect of pharyngeal incoordination that cause aspiration of secretion that is an important cause of death in the nonsurvivors.