The Association between Patent Ductus Arteriosus and Perinatal Infection in A Group of Low Birth Weight Preterm Infants

Objective: Patent ductus arteriosus (PDA) is an extremely common occurrence in very premature infants. Untreated symptomatic PDA may be associated with chronic lung disease. PDA has a major role in neonatal mortality and morbidity. We compared the efficacy and safety of oral versus intravenous ibuprofen for the pharmacological closure of PDA in low birth weight (LBW) preterm infants. Methods: A randomized, single-blinded, controlled study was performed on premature neonates at the neonatal unit, University Hospital for Obstetrics and Gynecology “Koço Gliozheni”, Tirana, Albania from January 2010 to December 2012. The study enrolled 68 preterm infants with a confirmed and significant PDA. The preterm infants received either intravenous or oral ibuprofen randomly as an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 48 h. Findings : 36 patients were treated with oral ibuprofen and 32 with intravenous ibuprofen during this period. After the first course of the treatment, the PDA closed in 30 (83.3%) of the patients assigned to the oral ibuprofen group versus 23 (71.8%) of those enrolled in the intravenous ibuprofen group (P=0.355). 15 patiens needed a second treatment course and they all (100%) had clinical signs of infection and positive blood culture. There was no reopening of the ductus after the closure. Conclusion: Our data indicate that, for LBW infants, the rate of early ductal closure was comparable and the adverse effects were fewer with oral ibuprofen in comparison to the intravenous route. Association of PDA with perinatal infection has a negative impact in pharmacological closure of the ductus, increasing the need for a second course of treatment or for surgery.Key Words: Prematurity, Perinatal Infection, Patent Ductus Arteriosus, Oral Ibuprofen, Intravenous Ibuprofen     

A 3-base pair deletion,c.9711_9713del,in DMD results in intellectual disability without muscular dystrophy

We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue, Leu3238, in the brain-specific isoform Dp71 of dystrophin. Linkage analysis supported causality as the mutation was present in the 7.6 cM linkage interval on Xp22.11–Xp21.1 with a maximum positive LOD score of 2.41 (MRX85 locus). Molecular modeling predicts that the p.(Leu3238del) deletion results in the destabilization of the C-terminal domain of dystrophin and hence reduces the ability to interact with β-dystroglycan. Correspondingly, Dp71 protein levels in lymphoblastoid cells from the index patient are 6.7-fold lower than those in control cell lines (P=0.08). Subsequent determination of the creatine kinase levels in blood of the index patient showed a mild but significant elevation in serum creatine kinase, which is in line with impaired dystrophin function. In conclusion, we have identified the first DMD mutation in Dp71 that results in ID without muscular dystrophy.     

High flow cytometric scores identify adverse prognostic subgroups within the revised international prognostic scoring system for myelodysplastic syndromes

The estimation of survival of myelodysplastic syndromes (MDS) and risk of progression into acute myeloid leukaemia is challenging due to the heterogeneous clinical course. The most widely used prognostic scoring system (International Prognostic Scoring System [IPSS]) was recently revised (IPSS‐R). The aim of this study was to investigate the prognostic relevance of flow cytometry (FC) in the context of the IPSS‐R. Bone marrow aspirates were analysed by FC in 159 patients with MDS. A flow score was calculated by applying the flow cytometric scoring system (FCSS). Patients were assigned to IPSS and IPSS‐R risk groups. The FCSS correlated with the World Health Organization classification, IPSS and IPSS‐R risk groups. Mild flow cytometric abnormalities were associated with significantly better overall survival (OS) and lower risk of disease evolution. The presence of aberrant myeloid progenitors was associated with transfusion dependency and disease progression. Most importantly, the FCSS identified prognostic subgroups within the IPSS‐R cytogenetic good risk and low risk group. Flow cytometric analysis in patients with MDS provides additional prognostic information and is complementary to the IPSS‐R. The addition of a flow cytometric score next to the clinical parameters within the IPSS‐R is a further refinement of prognostication of patients with MDS.     

Psychosocial Correlates of Suicidal Ideation in Rural South African Adolescents

Suicide is a prevalent problem among young people in Southern Africa, but prevention programs are largely absent. This survey aimed to identify the behavioral and psychosocial correlates of suicidal ideation among adolescents in Limpopo. A two-stage cluster sample design was used to establish a representative sample of 591 adolescents. Bivariate correlations and multiple linear regression analyses were conducted. Findings show that suicidal ideation is prevalent among adolescents. The psychosocial factors perceived social support and negative feelings about the family and the behavioral factors forced sexual intercourse and physical violence by the partner were found to increase the risk of suicidal ideation. Depression mediated the relationship between these psychosocial and behavioral risk factors and suicidal ideation. This study increased our understanding of the psychosocial and behavioral predictors of adolescent suicidal ideation. The findings provide target points for future intervention programs and call for supportive structures to assist adolescents with suicidal ideation.     

Periodontal inflamed surface area and C-reactive protein as predictors of HbA1c: a study in Indonesia

Periodontitis may exert an infectious and inflammatory burden, evidenced by increased C-reactive protein (CRP). This burden may impair blood glucose control (HbA1c). The aim of our study was to analyze whether periodontitis severity as measured with the periodontal inflamed surface area (PISA) and CRP predict HbA1c levels in a group of healthy Indonesians and a group of Indonesians treated for type 2 diabetes mellitus (DM2). A full-mouth periodontal examination, including probing pocket depth, gingival recession, clinical attachment loss, plaque index and bleeding on probing, was performed in 132 healthy Indonesians and 101 Indonesians treated for DM2. Using these data, PISA was calculated. In addition, HbA1c and CRP were analyzed. A validated questionnaire was used to assess smoking, body mass index (BMI), education and medical conditions. In regression analyses, it was assessed whether periodontitis severity and CRP predict HbA1c, controlling for confounding and effect modification (i.e., age, sex, BMI, pack years, and education). In healthy Indonesians, PISA and CRP predicted HbA1c as did age, sex, and smoking. In Indonesians treated for DM2, PISA did not predict HbA1c. Periodontitis may impair blood glucose regulation in healthy Indonesians in conjunction with elevated CRP levels. The potential effect of periodontitis on glucose control in DM2 patients may be masked by DM2 treatment. Clinical relevance: periodontitis may impair blood glucose control through exerting an inflammatory and infectious burden evidenced by increased levels of CRP.     

Deep brain stimulation of the forniceal area enhances memory functions in experimental dementia: The role of stimulation parameters

Deep brain stimulation (DBS) is currently being evaluated as a potential therapy in improving memory functions in Alzheimer’s disease. The target for DBS and the stimulation parameters to be used are unknown. Here, we implanted bilateral electrodes in the vicinity of the fornix, a key element of the memory circuitry, and applied DBS with different stimulation frequencies and amplitudes in an experimental model of dementia. Rats received scopolamine, a muscarinic acetylcholine receptor antagonist, to mimic memory impairment. Rats were then tested in the object location task with the following conditions: (i) with attachment of stimulation cable (off stimulation), and (ii) with DBS at various amplitudes (50 μA, 100 μA and 200 μA), 100 μs pulse width and 100 Hz or 10 Hz stimulation frequency. DBS reversed the memory impairing effects of scopolamine when compared to sham rats. We found that the fornix is not sensitive to the frequency of stimulation, but rather to current levels. With the most optimal stimulation parameter, we found no side-effects on anxiety levels and general motor activity. These findings identify the fornix as a key region in controlling spatial memory functions. DBS of this region, using tailored stimulation parameters, has the potential to improve memory functions in conditions characterised by memory impairment.     

CD34 marks angiogenic tip cells in human vascular endothelial cell cultures

The functional shift of quiescent endothelial cells into tip cells that migrate and stalk cells that proliferate is a key event during sprouting angiogenesis. We previously showed that the sialomucin CD34 is expressed in a small subset of cultured endothelial cells and that these cells extend filopodia: a hallmark of tip cells in vivo. In the present study, we characterized endothelial cells expressing CD34 in endothelial monolayers in vitro. We found that CD34-positive human umbilical vein endothelial cells show low proliferation activity and increased mRNA expression of all known tip cell markers, as compared to CD34-negative cells. Genome-wide mRNA profiling analysis of CD34-positive endothelial cells demonstrated enrichment for biological functions related to angiogenesis and migration, whereas CD34-negative cells were enriched for functions related to proliferation. In addition, we found an increase or decrease of CD34-positive cells in vitro upon exposure to stimuli that enhance or limit the number of tip cells in vivo, respectively. Our findings suggest cells with virtually all known properties of tip cells are present in vascular endothelial cell cultures and that they can be isolated based on expression of CD34. This novel strategy may open alternative avenues for future studies of molecular processes and functions in tip cells in angiogenesis.     

Prognostic scoring system for peripheral nerve repair in the upper extremity

So far, predictive models with individualized estimates of prognosis for patients with peripheral nerve injuries are lacking. Our group has previously shown the prognostic value of a standardized scoring system by examining the functional outcome after acute, sharp complete laceration and repair of median and/or ulnar nerves at various levels in the forearm. In the present study, we further explore the potential mathematical model in order to devise an effective prognostic scoring system. We retrospectively collected medical record data of 73 cases with a peripheral nerve injury in the upper extremity in order to estimate which patients would return to work, and what time was necessary to return to the pre‐injury work. Postoperative assessment followed the protocol described by Rosén and Lundborg. We found that return to pre‐injury work can be predicted with high sensitivity (100%) and specificity (95%) using the total numerical score of the Rosén and Lundborg protocol at the third follow‐up interval (TS3) as well as the difference between the TS3 and the total score at second follow‐up interval (TS2). In addition, the factors age and type of injured nerve (median, ulnar, or combined) can determine the time of return to work based on a mathematical model. This prognostic protocol can be a useful tool to provide information about the functional and social prospects of the patients with these types of injuries. © 2012 Wiley Periodicals, Inc. Microsurgery, 2013.