bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Screening for the LRRK2 R1441C and G2019S Mutations in Parkinsonian Patients from Campania
Authors: De Rosa Anna , De Michele Giuseppe , Guacci Anna , Carbone Rosa , Lieto Maria , Peluso Silvio , Picillo Marina , Barone Paolo , Salemi Fabrizio , Laiso Antonio , Saccà Francesco , Tessitore Alessandro , Pellecchia Maria Teresa , Bonifati Vincenzo , Criscuolo Chiara
Published: December 2019

Background: PARK8 is the most common known mendelian form of Parkinson's Disease (PD). It is due to mutations in the leucine-rich repeat kinase 2 (LRRK2) gene and G2019S is considered the most frequent mutation in the Caucasian population, in particular in the Southern Europe and Mediterranean countries. Objective: We assessed the frequency of the G2019S and R1441C/H/G mutations in 513 (311 M and 202 F) unrelated PD patients from Campania, in Southern Italy. Methods: Three hundreds and thirty-six patients presented a sporadic disease, and 177 had a familial history of PD or tremor. Three hundreds and eighty cases originated from the province of Naples. We compared our LRRK2 mutation carriers to idiopathic PD patients matched for recruiting center, gender, age and age at onset. Results: Thirteen patients (8 M and 5 F) carried the R1441C mutation and 4 (3 M and 1 F) the G2019S mutation, all in heterozygous state. All carriers originated from the province of Naples. No carriers of the R1441H or R1441G mutations were found. The LRRK2 mutation carriers were clinically similar to idiopathic PD patients. The R1441C and G2019S mutations are not rare causes of PD in Campania, especially in the province of Naples and among the familial cases, where the overall mutation prevalence is 6.8%. Conclusions: The R1441C prevalence was higher than that of G2019S (2.5% vs 0.8%), underlining the importance of the geographical differencies in LRRK2 mutation frequency for molecular screening and genetic counseling of PD patients.
Physical Activity in Advanced Parkinson's Disease: Impact of Subthalamic Deep Brain Stimulation
Authors: Daneault Jean-François , Sadikot Abbas F. , Barbat-Artigas Sébastien , Aubertin-Leheudre Mylène , Jodoin Nicolas , Panisset Michel , Duval Christian
Published: December 2019

Background: Maintaining a physically active lifestyle promotes general health. Recent studies have demonstrated that patients with Parkinson's disease (PD) fail to meet the suggested levels of physical activity and that targeted interventions do not always improve this behavior. One validated treatment for motor symptoms in PD is subthalamic stimulation (STN DBS). Objective: Assess whether motor symptom improvement following STN DBS translated into increased physical activity behavior. Methods: Twenty patients with PD scheduled for bilateral STN DBS filled-out the Phone-FITT physical activity questionnaire and the SF-36 quality of life questionnaire prior to surgery and 6 to 9 months postoperatively. Data were compared to age- and gender-matched healthy controls. Results: Our results demonstrate that PD patients' quality of life is significantly lower than healthy controls. While STN DBS improves motor symptoms in the intermediate term, it only improves some aspects of quality of life related to physical function. Furthermore, STN DBS does not modify physical activity behavior measured by the Phone-FITT, whether for household or recreational activities. Conclusion: The current study demonstrates that the motor improvements observed after STN DBS do not lead to systematic improvements in all aspects of quality of life or increased levels of physical activity. This highlights the need to develop and implement intervention strategies to promote an active lifestyle in this population, even if clinical improvement is evident following surgery.
Saccadic Eye Movements are Related to Turning Performance in Parkinson Disease
Authors: Lohnes Corey A. , Earhart Gammon M.
Published: December 2019

Background. Persons with Parkinson disease (PD) experience difficulty turning, leading to freezing of gait and falls. We hypothesized that saccade dysfunction may relate to turning impairments, as turns are normally initiated with a saccade. Objective. Determine whether saccades are impaired during turns in PD and if characteristics of the turn-initiating saccade are predictive of ensuing turn performance. Methods. 23 persons with PD off medication and 19 controls performed 90 and 180 degree in-place turns to the right and left. Body segment rotations were measured using 3-D motion capture and oculomotor data were captured using a head-mounted eye tracking system and electrooculography. Total number of saccades and the amplitude, velocity, and timing of the first saccade were determined. Results. Turn performance (turn duration, number of steps to turn) was impaired in PD (p < 0.05). PD performed more saccades, and the velocity and timing of the first saccade was impaired for both turn amplitudes (p < 0.05). Amplitude of the first saccade was decreased in PD during 180 degree turns. Turn duration correlated with oculomotor function. Characteristics of the first saccade explained 48% and 58% of the variance in turn duration for 90 and 180 degree turns, respectively. Conclusions. Turning performance is impaired in PD and may be influenced by saccade dysfunction. An association between saccade function and turning performance may be indicative of the key role of saccades in initiating proper turning kinematics. Future work should focus on improving saccade performance during functional tasks and testing the effects of therapeutic interventions on related outcomes.
Generation of Ferric Iron Links Oxidative Stress to α-Synuclein Oligomer Formation
Authors: Levin Johannes , Högen Tobias , Hillmer Andreas S. , Bader Benedikt , Schmidt Felix , Kamp Frits , Kretzschmar Hans A. , Bötzel Kai , Giese Armin
Published: December 2019

Background: Synucleinopathies such as Parkinson's disease are characterized by the deposition of aggregated α-synuclein in affected brain areas. As genes involved in mitochondrial function, mitochondrial toxins, and age-related mitochondrial impairment have been implicated in Parkinson's disease pathogenesis, an increase in reactive oxygen species resulting from mitochondrial dysfunction has been speculated to induce α-synuclein aggregation. In vitro, pore-forming, SDS-resistant α-synuclein oligomers are formed in presence of ferric iron and may represent an important toxic particle species. Methodology/Principal findings: We investigated the interplay of reactive oxygen species, antioxidants and iron oxidation state in regard to α-synuclein aggregation using confocal single particle fluorescence spectroscopy, Phenanthroline spectrometry and thiobarbituric acid reactive substances assay. We found that the formation of α-synuclein oligomers in presence of Fe3+ is due to a direct interaction. In contrast, oxidizing agents and hydroxyl radicals generated in the Fenton reaction did not directly affect α-synuclein oligomerization. However, reactive oxygen species could enhance aggregation via oxidation of ferrous to ferric iron when iron ions were present. Conclusions/Significance: Our data thus indicate that oxidative stress affects α-synuclein aggregation via oxidation of iron to the ferric state. This provides a new perspective on the role of mitochondrial toxins and mitochondrial dysfunction in the pathogenesis of Parkinson's disease.
Colonic Neuropathology is Independent of Olfactory Dysfunction in Parkinson's Disease
Authors: Lebouvier Thibaud , Pouclet Hélène , Coron Emmanuel , Drouard Anne , N'Guyen Jean-Michel , Roy Monica , Vavasseur Fabienne , Bruley des Varannes Stanislas , Damier Philippe , Neunlist Michel , Derkinderen Pascal , Rouaud Tiphaine
Published: December 2019

Olfactory dysfunction (OD) and constipation are two frequent and early non-motor features of Parkinson's disease (PD). Colonic PD neuropathology, the putative cause of constipation, can be analyzed and quantified using routine colonic biopsies and parallels disease severity. The present study was aimed at investigating whether the severity of neuropathology in the colon in PD is related to OD. Twenty-six PD patients were included. Colonic neuropathology, i.e., the density of Lewy pathology and the number of submucosal neurons, was unrelated to OD as assessed using the University of Pennsylvania Smell Identification. This suggests that unlike colonic Lewy pathology, OD is unrelated to disease severity.
James Parkinson: The Man Behind the Shaking Palsy
Authors: Lewis Patrick A.
Published: December 2019

James Parkinson occupies a unique position in the history of Parkinson's disease. As the man responsible for originally identifying and describing the disease that he called the Shaking Palsy, his name is familiar to anybody with a connection with the disease – patients, carers, clinicians and members of the general public alike. This review summarises the life and career of one of the most recognizable names in neurology.
Changes in Sphingomyelin Level Affect Alpha-Synuclein and ABCA5 Expression
Authors: Kim Woojin Scott , Halliday Glenda M.
Published: December 2019

The pathological hallmark of Parkinson's disease (PD) is the presence of aggregated α-synuclein associated with lipids. Substantial evidence now exists to indicate that α-synuclein binds and interacts with regions of membranes that are enriched in lipids (lipid rafts). Lipids are transported around the brain by a group of proteins called ATP-Binding Cassette subfamily A (ABCA) transporters and in recent years there has been mounting evidence indicating that ABCA transporters regulate a number of neurodegenerative disease processes. Only recently a genome-wide association study reported that ABCA5 was genetically associated with a reduced risk for PD. However, very little is known about the role of lipids and ABCA5 in the pathological process of PD. In this study we investigate the impact of the lipid-raft lipid sphingomyelin on α-synuclein and ABCA5 expression. We also investigate in which primary human brain cells ABCA5 is expressed and whether the expression of ABCA5 is altered in PD brain. When SK-N-SH neuronal cells were treated with sphingomyelin the expression of both α-synuclein and ABCA5 was significantly increased, indicating sphingomyelin as a potential substrate for the ABCA5 transporter. ABCA5 was strongly expressed in neurons and moderately in microglia, with only weak expression observed in astrocytes and oligodendrocytes. The expression of ABCA5 was significantly elevated in PD brains compared to age- and gender-matched control brains, possibly as a protective response to the disease. These data provide new evidence indicating that lipid is important for α-synuclein pathology in PD.
Automated Assessment of Bradykinesia and Dyskinesia in Parkinson's Disease
Authors: Griffiths Robert I. , Kotschet Katya , Arfon Sian , Xu Zheng Ming , Johnson William , Drago John , Evans Andrew , Kempster Peter , Raghav Sanjay , Horne Malcolm K.
Published: December 2019

There is a need for objective measures of dyskinesia and bradykinesia of Parkinson's disease (PD) that are continuous throughout the day and related to levodopa dosing. The output of an algorithm that calculates dyskinesia and bradykinesia scores every two minutes over 10 days (PKG: Global Kinetics Corporation) was compared with conventional rating scales for PD in PD subjects. The algorithm recognises bradykinesia as movements made with lower acceleration and amplitude and with longer intervals between movement. Similarly the algorithm recognises dyskinesia as having movements of normal amplitude and acceleration but with shorter periods without movement. The distribution of the bradykinesia and dyskinesia scores from PD subjects differed from that of normal subjects. The algorithm predicted the clinical dyskinesia rating scale AIMS with a 95% margin of error of 3.2 units compared with the inter-rater 95% limits of agreement from 3 neurologists of −3.4 to +4.3 units. Similarly the algorithm predicted the UPDRS III score with a margin of error similar to the inter-rater limits of agreement. Improvement in scores in response to changes in medication could be assessed statistically in individual patients. This algorithm provides objective, continuous and automated assessment of the clinical features of bradykinesia and dyskinesia in PD.
Knowledge about adverse drug reactions reporting among healthcare professionals in Nepal
Authors: KC Santosh , Tragulpiankit Pramote , Edwards I. Ralph , Gorsanan Sarun
Published: December 2019

OBJECTIVE: To investigate the knowledge about ADRs and ADR reporting among healthcare professionals working at four regional pharmacovigilance centers (RPCs) of Nepal. METHODS: It was a cross sectional study, done by a survey using a validated self-administered structured questionnaire. The questionnaire was distributed to 450 healthcare professionals working at four RPCs. RESULTS: The overall response rate was 74%. Only 53% and 38% of respondents knew about the existence of National Pharmacovigilance Centre (NPC) and RPC, respectively. Among the respondents, 29% and 33% did not know what a Type A and Type B ADR was. Similarly, 30% and 45% were not aware of the common types of ADRs or the thalidomide tragedy. Only, 9% knew about Uppsala Monitoring Centre (UMC) and only 10% answered correctly about the Naranjo algorithm as a causality assessment tool for ADRs. Of the respondents, only 19% knew about spontaneous reporting system and only 18% were aware about its drawbacks. The overall mean score on knowledge about ADR among healthcare professionals was 7.64 ± 2.38 out of the maximum possible score of 12. Whereas, the overall mean score of knowledge about ADR reporting was 3.95 ± 1.78 out of maximum possible score of 11. CONCLUSION: Healthcare professionals working at four RPCs of Nepal have some knowledge about ADRs themselves but limited knowledge about ADR reporting. There is an urgent need of action to be taken by RPCs at the regional level and NPC at the national level to improve knowledge and ADR reporting by healthcare professionals.
Medication administration errors among paediatric nurses in Lagos public hospitals: An opinion survey
Authors: Oshikoya K.A. , Oreagba I.A. , Ogunleye O.O. , Senbanjo I.O. , MacEbong G.L. , Olayemi S.O.
Published: December 2019

OBJECTIVE: There is paucity of data on paediatric medicine administration error (MAE) in developing countries. This study aimed to investigate the experience of MAEs among paediatric nurses working in public hospitals in Lagos, Nigeria. DESIGN: A confidential, self-reporting questionnaire was the instrument for the study. SETTING: Public hospitals in Lagos, Nigeria with established paediatric services and departments. PARTICIPANTS: Paediatric nurses. METHODS: The questionnaire was administered to 75 nurses working in public hospitals in Lagos to obtain information on the experience of medication errors during their entire career, as well as to know their views on the nature of MAEs and the contributing factors. RESULTS: Fifty nurses responded to give a response rate of 66.7%. All the participants were females with a mean ± s.d age of 35.3 ± 10.7 years. Thirty two (64%) had committed at least one medication error over the course of their career. Wrong dose error (24; 48%) and wrong timing of medicine administration (20; 40%) were the MAEs frequently committed by the participants. The consequences of the errors included shock (23; 46%), restlessness (21; 42%), disorientation (11; 22%), and respiratory depression (10; 20%). Increased workload (26; 52%) and not double checking medicine doses (12; 24%) were the major factors the nurses perceived to be contributing to MAEs. Only 15(30%) nurses had reported MAEs to their superiors. Fear of intimidation, retribution or being punished (11; 22%) and lack of policies in place to report errors (13; 26%) were the two major barriers to reporting MAEs. Half (50%) of the nurses indicated that policies were available in their work places to prevent medication errors. CONCLUSIONS: Medication administration errors were frequently committed by the participants and resulted in some inconsequential effects, morbidity and deaths. Appropriate measures should be implemented to prevent future occurrences of MAEs.
Effect of infection control strategy on knowledge, attitude and practice towards hepatitis B transmission and prevention in vulnerable populations
Authors: Al-Tawil M.M. , El-Gohary E.E. , El-Sayed M.H.
Published: December 2019

BACKGROUND: Health care workers (HCWs) and hematological patients needing blood/ blood product transfusion are particularly vulnerable to blood born infections (BBI) including viral hepatitis. OBJECTIVE: To evaluate knowledge, attitude and practice (KAP) of these target groups regarding viral hepatitis B (HBV) transmission and its change with implementing infection control policy and procedures. METHODS: An anonymous questionnaire with closed questions was used to evaluate KAP including vaccination status in 2 target groups, in Children Hospital, Ain Shams University, Cairo, Egypt: 184 nurses and 210 children and adolescents with blood diseases. One year after instituting infection control as a part of hospital procedures, the same questionnaire was reused to evaluate KAP towards HBV. RESULTS: Baseline knowledge regarding HBV transmission, sequelae and preventive measures, was poor in both groups. Among nurses, only 62% wore gloves on withdrawing or giving blood to patients, 43.5% routinely washed hands between patients and 37.5% reported exposure after sharp injury. Only 38% of patients and 40% of nurses received HBV vaccination. Targeted infection control policy and procedures significantly improved KAP regarding HBV in both groups. Vaccination coverage significantly increased and reached 88.7% for nurses and 72% for patients. CONCLUSIONS: Hospital based infection control units with established policy and procedures against BBI significantly improved KAP towards HBV including a significant increase in vaccination intake.
All I have is a void: Women's perceptions of the benefits and side effects of ECT
Authors: Ejaredar Maede , Hagen Brad
Published: December 2019

BACKGROUND: Recent reviews of the benefits and risks associated with electroconvulsive therapy (ECT) have often reported mixed and conflicting results. Although there are very few qualitative studies on ECT, qualitative research offers the advantage of in-depth explorations into how people perceive and experience ECT. OBJECTIVE: The objective of this qualitative study was to explore women's experiences and perceptions of the benefits and side effects associated with having ECT. METHODS: The authors used narrative inquiry and in-depth interviews to obtain nine women's accounts and stories of ECT, focusing particularly on their accounts of perceived benefits and side effects associated with ECT. RESULTS: Qualitative thematic analysis of the interviews with nine women resulted in four main themes emerging from the interviews: “it's sort of like housecleaning,” “I don't remember the wedding,” made me stupider,” and “putting them in a cage with a bear.” CONCLUSIONS: Three of the women were able to articulate some perceived benefit arising from ECT, although these women also acknowledged the benefits did not last more than two weeks. The majority of women complained of significant and persistent autobiographical memory loss, cognitive deficits, and fear of the procedure.
The validity of the Nordic patient safety culture questionnaire (TUKU)
Authors: Reiman Teemu , Silla Inmaculada , Pietikäinen Elina
Published: December 2019

BACKGROUND: Patient safety culture (PSC) has been postulated to have a significant influence on the quality of health care. OBJECTIVE: This study aims to evaluate the psychometric properties of the TUKU PSC questionnaire. METHODS: The questionnaire development was based on the view that patient safety constitutes not only the absence of adverse events, but also the presence of certain organizational attributes that enable safety. The TUKU questionnaire has two parts: a measure of psychological dimensions, and a measure of employees' perceptions of organizational functions. The TUKU questionnaire was validated using a sample of 1162 health care professionals from seven Finnish health care organizations. Two studies were carried out, one focusing on construct validity and the other on criterion validity. RESULTS: Regarding construct validity, the empirical model matched the theory quite well. The results of Study 2 concerning criterion validity were more ambiguous. Four of the organizational dimensions and two of the psychological dimensions were related to patient safety incidents occurring 16 months after administering the questionnaire. CONCLUSIONS: The study provided evidence on the key organizational dimensions that comprise patient safety culture and affect patient safety. The study further contributed towards validation of an instrument for measuring these dimensions.
Guidewire retention following central venous catheterisation: A human factors and safe design investigation
Authors: Horberry Tim , Teng Yi-Chun , Ward James , Patil Vishal , Clarkson P. John
Published: December 2019

BACKGROUND: Central Venous Catheterisation (CVC) has occasionally been associated with cases of retained guidewires in patients after surgery. In theory, this is a completely avoidable complication; however, as with any human procedure, operator error leading to guidewires being occasionally retained cannot be fully eliminated. OBJECTIVE: The work described here investigated the issue in an attempt to better understand it both from an operator and a systems perspective, and to ultimately recommend appropriate safe design solutions that reduce guidewire retention errors. METHODS: Nine distinct methods were used: observations of the procedure, a literature review, interviewing CVC end-users, task analysis construction, CVC procedural audits, two human reliability assessments, usability heuristics and a comprehensive solution survey with CVC end-users. RESULTS: The three solutions that operators rated most highly, in terms of both practicality and effectiveness, were: making trainees better aware of the potential guidewire complications and strongly emphasising guidewire removal in CVC training, actively checking that the guidewire is present in the waste tray for disposal, and standardising purchase of central line sets so that differences that may affect chances of guidewire loss is minimised. CONCLUSIONS: Further work to eliminate/engineer out the possibility of guidewires being retained is proposed.
Application of the IHI Global Trigger Tool in measuring the adverse event rate in a Turkish healthcare setting
Authors: Kurutkan Mehmet Nurullah , Usta Esra , Orhan Fatih , Simsekler M. C. Emre
Published: December 2019

BACKGROUND: The goal of this study was to measure an adverse event rate and determine the potential usefulness of the Institute for Healthcare Improvement's Global Trigger Tool (GTT). Besides using the GTT to measure the adverse event rate, a comparison was also made with the internal Voluntary Reporting Notification System (VRNS) to identify and compare the strengths and weaknesses of the two approaches. METHOD: Retrospective data were collected from reported patient safety incidents covering a one-year period at Duzce University Hospital, Turkey. Using a range of selection criteria, a total of 219 patient records were selected and then reviewed by a trained GTT team, to investigate the positive triggers in the content of the patient records. RESULTS: It was determined that adverse events per 1000 patient days totalled 80.72. Adverse events per 100 admissions were 29.39, and the rate of admissions with adverse events was 16.67%. The comparison between the GTT and the VRNS showed that the GTT is 19 times more sensitive than the VRNS in the adverse event evaluation process. CONCLUSION: This is the first published study of the rate of adverse events in a Turkish healthcare setting using the GTT. It was found that the GTT was applicable in this setting, yielding more accurate measurement of the adverse event rate. However, the content of the GTT should be adjusted regarding the standards and documentations used in the Turkish healthcare system to be more useful.
Drug safety and Health Canada
Authors: Lexchin Joel
Published: December 2019

The Food and Drugs Act theoretically gives Health Canada considerable authority in dealing with safety issues but there are also significant limitations in the legislation. Furthermore, the priorities of Health Canada are skewed in favour of rapid approval of new drugs at the expense of the postmarketing pharmacosurveillance system as judged by how much money and many personnel are allocated to each activity. Health Canada has explicitly rejected developing quantitative standards for evaluating its postmarketing pharmacosurveillance system. In addition to lacking standards in this area, it does not monitor whether or not its communications to professionals and the public have had the desired effect in terms of changing the way that drugs are prescribed and used. Health Canada continues to treat safety information that companies submit as confidential business information. What safety information it does release is insufficient to allow an adequate independent assessment of a drug’s safety. Progressive licensing is a new regulatory model that would allow Health Canada to retain control over a drug throughout the product's entire lifecycle. In its initial incarnation progressive licensing would have actually further strengthened Health Canada’s reliance on the industry for information and would have worked to enhance regulatory secrecy.
Perceptions of Adult ADHD
Authors: Noury Joanna Le , Tatineni Ranjit Kumar , Healy David
Published: December 2019

A survey was carried out of all consultant psychiatrists and a sample of senior healthcare professionals in North Wales to establish attitudes towards Adult ADHD following the recent publication of NICE guidelines on the condition. Although the sample size was relatively small (N = 50 consultants) it should be noted that 100% completion rate was achieved which was supplemented with responses from twelve senior ward staff.The survey results showed an increasing appreciation of the possible prevalence of Adult ADHD. Considerable variation was observed between consultants in different specialist areas, with child and adolescent mental health consultants showing more consistent beliefs and adult mental health consultants showing a shift in recognition of Adult ADHD. This survey aimed to map changing attitudes towards Adult ADHD. From a therapeutic perspective it makes sense to recognise the reality of the condition. However it should also be acknowledged that perceptions of the prevalence of such conditions may in part be tied into effective marketing.
Acceptability of an education computer multimedia on safe use of medication in patients and family members
Authors: See Lai-Chu , Peng Pei-I. , Lin Na-Ling , Lai Hui-Ju , Chang Yi-Hua , Jean Wen-Chyi , Wang Chao-Hui
Published: December 2019

Background: Programs for improving safety in medication often ignore the patient’s perspective although patients are usually the victims of medication errors. Therefore, educating patients or family members to participate in safety prevention on medication use during care delivery is essential. The aim was to develop a computer education multimedia on patient’s safe use of medication, and evaluate its acceptability and short-term effect. Methods: The one group pre- and post-training design was used in outpatient or inpatient setting at Chang Gung Memorial Hospital, where located at northern Taiwan. A questionnaire about the past and future practice of medication use, and their satisfaction towards the multimedia was asked. Results: One hundred twenty two participants were enrolled. The score of pretest were higher in family members than that in the patients (p = 0.0152). After showing the education multimedia, significant increase on the posttest was seen in both the patients (0.43 ± 0.6, p < 0.0001) and the family members (0.32 ± 0.6, p < 0.0001). Overall satisfaction was 98.2%. Conclusion: Our education multimedia had short-term effect on raising the participants’ awareness towards the safe use of medication. Their satisfaction of the multimedia was very high.
Rapid synthesis of some medicinally important hexahydro-s-triazine	derivatives incorporating benzothiazole
Authors: Pareek Pawan K. , Mithlesh  , Pareek Deepak , Chaudhary Manish , Pareek Arun , Kant Ravi , Ojha Kishan G.
Published: December 2019

A series of 2,4,6-trisubstituted 1,3,5-tris (benzothiazol-2-yl) hexahydro-1,3,5-triazine derivatives (3) have been synthesized by condensation of substituted benzothiazoles with 2,4,6-trisubstituted 1,3,5-trioxane by conventional as well as microwave irradiation (solvent free and solid support) methods. All compounds were tested for antiproliferative activity and entomological activity. The microwave irradiation technique gives better yield and reaction completion in a shorter period of time. Among solid supported microwave irradiation better yields are obtained with acidic alumina as compared to silica, neutral alumina and basic alumina.The results of biological activities prompted us that change in substitution pattern in benzothiazolyltriazine derivatives may cause marked effect on their antiproliferative activity.
Synthesis and structural characterization of triorganotin(IV)	methoxyacetates: Correlation of $^{13}$C CPMAS NMR	spectroscopy with single crystal structure
Authors: Amini Mostafa M. , Azadmehr Amirreza , Najafi Ezzatollah , Hadipour Nasser , Chen Chung-Der , Chen Chun-Jung
Published: December 2019

The triorganotin(IV) derivatives of methoxyacetic acid, methoxyacetatotriphenyltin(IV) (1), methoxyacetatomethyldiphenyltin(IV) (2), and methoxyacetatotriphenyltin(IV) (3) were synthesized by the reaction of methoxyacetic acid with Ph $_{3}$ SnCl, Ph $_{2}$ MeSnI, and Me $_{3}$ SnCl, respectively, with the aid of potassium iso-propoxide. Compounds 1–3 were characterized by elemental analysis, mass spectrometry, infrared spectroscopy (IR), and $^{1}$ H, $^{13}$ C, $^{119}$ Sn NMR, and $^{13}$ C CPMAS NMR. The molecular structures of the three complexes were determined by single-crystal X-ray diffraction. Crystallography shows that all three complexes adopt polymeric trans-C $_{3}$ SnO $_{2}$ trigonal bipyramidal structures with the oxygen atoms occupying axial positions. The X-ray structures reveal two independent, non-symmetric, but essentially identical molecules in the crystallographic asymmetric unit of 1 and 3, in which they link to each other by a bridged methoxyacetato ligand. The $^{13}$ C CPMAS NMR spectroscopy of 1 and 3, with two sets of signals for the groups linked to tin, is consistent with the two independent trigonal bipyramids in the asymmetric unit. The prepared compounds show much higher solubility in ethanol in comparison to acetate derivatives.
Prenatal alcohol exposure and its repercussion on newborns
Authors: Baña A. , Tabernero M.J. , Pérez-Muñuzuri A. , López-Suárez O. , Dosil S. , Cabarcos P. , Bermejo A. , Fraga J.M. , Couce M.L.
Published: December 2019

BACKGROUND: Alcohol consumption during pregnancy, even when moderate, implies a risk of impaired neurodevelopment, physical impairments and malformations. Its early identification is essential for establishing preventive measures to diminish disabilities among newborns. METHODS: To determine the frequency of consumption of substance use in pregnant women, we have used the techniques of gas chromatography/mass spectrometry and liquid chromatography/tandem mass spectrometry to detect drugs and markers of chronic consumption of alcohol in meconium. We performed a prospective study during a period of 10 months among 110 infants in our hospital, assessing anthropometry, neuromuscular development and determination of toxic substances in urine and meconium. Furthermore, meconium analysis identified fatty acid ethyl esters (FAEEs) and ethyl glucuronide (Etg). We also conducted a survey regarding the obstetric history, toxic habits, and employment status of the mothers. RESULTS: According to early detection markers analyzed in meconium (FAEE >1000 ng/g and/or Etg >50 ng/g meconium), 34.65% of pregnant women consumed alcohol during pregnancy, and 17% were positive for both markers. Within the positive cases, 50% of those exceeding a FAEE's value of 5000 ng/g in meconium had low birth-weight children. Only 5/110 mothers (4.5%) admitted to occasional alcohol consumption during pregnancy. Nobody admitted to frequent intake. The cocaine test was positive in three cases; two of them were positive for alcohol as well. CONCLUSION: As expected, many screening devices do not accurately capture use during pregnancy and supplemental methods such as meconium analysis of biomarkers of chronic alcohol consumption may be warranted.
Changes in hematocrit following a blood transfusion does not influence the risk for necrotizing enterocolitis: A case-control study
Authors: Lawrence S.M. , Nandyal R. , Hallford G. , Anderson M. , Hart N.
Published: December 2019

OBJECTIVE: Transfusion Associated Necrotizing Enterocolitis (TANEC) is defined as the onset of necrotizing enterocolitis (NEC) within 48 hours of receiving a blood transfusion in preterm neonates. We wanted to determine if hematocrit changes following blood transfusions were associated with disease development. PATIENTS AND METHODS: This is a case-control analysis of inborn neonates ≤32 weeks' gestational age, from January 1, 2007 and December 31, 2010, who were diagnosed with Bell stage II or greater NEC. Those meeting TANEC criteria were identified and an analysis completed to determine if beginning or ending hematocrit values were associated with an increased risk for disease development. RESULTS: Nineteen of forty-nine (39%) infants with NEC met the criteria for TANEC. We found no differences in gestational age at birth or birth weight in our experimental groups. The degree of illness including PDA, IVH, central line use, and respiratory support 48 hours prior to disease onset was also similar between groups. Those with TANEC had higher modified Bell staging of NEC and were more likely to be receiving full enteric feeds at the time of NEC onset. No statistically significant differences were found in hematocrit levels prior to or following the blood transfusion closest to NEC onset in the TANEC group, as compared to classic NEC (CNEC) or control infants. CONCLUSION: The onset of NEC following transfusion occurs with a frequency that invites investigation regarding causation. Our data indicates no association between the beginning and ending hematocrit values and TANEC in our patient population.
Serum apelin in early-onset neonatal sepsis: Is it diagnostic?
Authors: Gad G.I. , Ismail R.I.H. , El-Masry S.A. , Gouda H.R.
Published: December 2019

OBJECTIVE: To evaluate the diagnostic value of serum apelin in early-onset neonatal sepsis in full term neonates. Apelin is a proinflammatory adipocyte-derived factor that participates in vascular wall inflammation. STUDY DESIGN: Case-control study was conducted on 60 full term neonates, 30 cases with early-onset neonatal sepsis and 30 healthy matched controls. Complete blood counts, C-reactive protein, blood cultures, plasma lactate, and serum apelin concentrations (measured by enzyme-linked immunosorbent assay) were determined initially at the time of sepsis diagnosis and 4 days after starting treatment for cases. Only basal serum apelin concentrations were measured for control group. RESULTS: Apelin was detected in all neonates and concentrations were positively correlated to sepsis scores, plasma lactate and CRP. Neonates with sepsis had significantly elevated concentrations (8 folds increase) of serum apelin concnetration as compared to controls [median (IQR): 65.16(46.90) and 7.969(11.36) pg/ml, respectively]. Moreover initial serum apelin concentration measured in cases with culture proven neonatal sepsis was significantly higher than those with negative-culture clinical sepsis (mean ± SD: 73.53 ± 31.77 and 45.22 ± 5.9 respectively, p = 0.0001). The best cutoff value of serum apelin to diagnose early-onset neonatal sepsis was 30.225 pg/ml with a sensitivity of 100% and a specificity of 97%. CONCLUSION: Serum apelin may have a diagnostic value in early-onset neonatal sepsis.
Unusual case of pericardial tamponade due to umbilical venous	catheterization in a newborn with congenital chylothorax: Case report and	review of the literature
Authors: Mueller Andreas , Franz Axel , Bartmann Peter , Heep Axel
Published: December 2019

Pericardial tamponade occurs rarely as severe complication of umbilical venous catheterization. We describe a preterm infant with congenital hydrothorax and mild hydrops fetalis who required umbilical venous catheterization for inotropic support and parenteral nutrition. The correct position of the UVC was verified by echocardiography and chest x-ray. The infant developed respiratory failure because of an increasing right sided pleural effusion at day 4 resulting in a mediastinal shift to the left side. During drainage of the pleural effusion the infant suddenly presented with decreasing blood pressure and subsequent bradycardia requiring resuscitation. Immediate transthoracic echocardiography revealed a cardiac tamponade due to pericardial effusion and pericardiocentesis was successfully performed promptly. The patient's conditions stabilized and he was discharged from hospital at 6 weeks postnatal age without apparent sequelae. Cardiac tamponade may occur despite correct position of the umbilical venous catheter. In our case the mediastinal shift presumably caused the atrial perforation by the catheter.
Hypoxic-ischemic encephalopathy in preterm infants
Authors: Schmidt John W. , Walsh William F.
Published: December 2019

Objective: To determine both the incidence of perinatal hypoxic ischemic encephalopathy (HIE) in a group of preterm infants 32–36 weeks gestational age at a single center and the outcomes of these patients.

Study design: The number of infants 32–36 weeks gestational age without major congenital anomalies born at Vanderbilt University Hospital between January 1, 2002 and June 30, 2008 was determined and a retrospective chart review was performed on those infants with a 5-minute Apgar score of less than 6. Infants were considered to have experienced perinatal HIE if they met all of the following criteria:

5-minute Apgar score less than 6

Cord or initial patient blood pH less than 7.00 or base deficit greater than 15 (mmol/L)

Evidence of encephalopathy at or shortly after birth (seizures, hypotonia)

History of a sentinel event at the time of delivery

No other cause of encephalopathy (sepsis, hypermagnesemia, hemorrhage, hyponatremia, drug induced)

Preterm infants with 5-minute Apgar score less than 6 not meeting all of the criteria were considered not to have had perinatal HIE. A poor outcome was defined as death, or cerebral palsy, or neurodevelopmental impairment, or bilateral deafness, or bilateral blindness. If no follow-up data was available, the patient was recorded as being alive at discharge and considered to be normal.

Results: Between January 1, 2002 and June 30, 2008 there were 1,325 infants 32–36 weeks gestational age born at Vanderbilt University Medical Center. The incidence of perinatal HIE in these patients was 12/1325 (0.9%). 58.33% of these patients suffered poor outcomes.

Conclusion: With a similar incidence and experience of adverse sequelae as the term infant, preterm infants 32–36 weeks in gestation with perinatal HIE should be considered for future randomized controlled studies for treatment of this potentially devastating injury.
Bladder pressure and intra-abdominal hypertension in sick neonates
Authors: Gerstmann Dale R. , Null, Jr. Donald M.
Published: December 2019

Objective: To define the range of intra-abdominal pressure (IAP) in sick neonates using surrogate measurements of bladder pressure.

Methods: Neonatal intensive care unit (NICU) patients requiring an indwelling urinary catheter were enrolled in the study. A bladder pressure monitoring system was attached to the catheter and measurements recorded every 2–4 h.

Results: Data were collected on 30~neonates. Median birth weight, gestational age, and duration of study were 2580 g, 37 wk, and 5.5 d, respectively. 1219 measurements were obtained with median (interquartile range)= 8 (3–10) mmHg and 90th percentile =13 mmHg. 18 neonates (60%) required abdominal surgery and 85% of IAP values > 90th percentile occurred post operatively (p< 0.001). 72% (13/18) of post operative patients had IAP > 90th percentile compared to 18% (2/12) of non surgical patients (p=0.008).

Conclusions: Measuring IAP in sick neonates can be done as part of neonatal intensive care. The time of highest risk for elevated IAP appears to be in the post-operative period.
Spontaneous perforation of Meckel's diverticulum in an extremely premature baby
Authors: Anay K. , Ramesh N. , Peter R. , Varadarajan K.
Published: December 2019

A 24 3/7 weeks gestation infant weighing 740 grams developed intestinal perforation. A perforated Meckel's diverticulum was revealed at exploratory laparotomy. This is the first reported case of Meckel's diverticulum presenting with perforation at this gestation in the United Kingdom. In the past 25 years, there are only 8 published cases of perforated Meckel's diverticula in neonatal age group.
Visible blood in the stool in a neonatal intensive care unit
Authors: Cordero L. , Giannone P.J. , Valentine C.J. , Coley B.D. , Nankervis C.A.
Published: December 2019

Background: Visible blood in the stool (VBS) and the appearance of gas within the bowel wall on radiographs, pneumatosis intestinalis, are the two major signs used to diagnose necrotizing enterocolitis (NEC). We experienced a four-fold increase in the incidence of VBS that was not associated with additional morbidities. Objective: To identify three new different diagnostic entities that would have been otherwise labeled as NEC. Methods: In this retrospective study we collected data on all neonates recognized with VBS; all of them had abdominal radiographs. Neonates were classified into three groups; 1) Benign pneumatosis coli (Pcoli) group (n = 46): included neonates with VBS and pneumatosis intestinalis on radiographs but no other clinical or laboratory abnormalities, 2) Classic NEC group (n = 39): included neonates with VBS and pneumatosis intestinalis, that was associated with clinical instability and/or laboratory abnormalities, and 3) Isolated VBS group (n = 46): included neonates with VBS without radiographic pneumatosis, clinical signs, or laboratory abnormalities. Results: Group 1 infants were of older gestational age when compared to Group 2 infants; the majority (89%) of the Benign Pcoli neonates was ≥34 weeks, whereas the majority (79%) of Classic NEC neonates was ≤33 weeks. The median postnatal age at the time of VBS was 7, 13 and 8 days for the three groups, respectively. Surgery (n = 13) and death (n = 6) were reported only in Classic NEC group. In the Isolated VBS group, the recognized blood was attributed to viral gastroenteritis (n = 3), anal fissure (n = 6), swallowed maternal blood (n = 9), and milk protein intolerance (n = 9), while the etiology was undetermined in 19 neonates. Conclusion: Although risk for surgery and mortality were high in Classic NEC, all neonates who presented with Benign Pneumatosis Coli or Isolated VBS had benign course and they all survived. Clinical and laboratory findings at the time of presentation of VBS are essential to differentiate these three diagnostic entities, and could possibly help avoidance of prolonged fasting and use of antibiotics.
The inverse association between gastroschisis and gestational hypertension
Authors: Payne N.R. , Pfleghaar K.M. , Blauer C. , Finkelstein M. , Olsen S.
Published: December 2019

Objective: Examine the relationship between maternal gestational hypertension (GH) and gastroschisis. Study design: This retrospective, observational study used a local dataset of 30 300 NICU patients and 3 429 498 U.S. birth certificate records to examine the prevalence of GH using univariate and logistic regression. Since body mass index (BMI) was not available in the data, we used Monte Carlo simulation of BMI followed by logistic regression to estimate the influence of this missing variable in the birth certificate data. Results: In the local dataset, maternal GH was lower in mothers of gastroschisis cases compared to the mothers of all other NICU admissions (0/188 vs. 4 351/30 112 [14.5%], p < 0.001). Adjusting for covariates, the odds ratio (OR) for GH among mothers of gastroschisis patients was 0.04 (95% confidence interval [CI] = 0.01–0.28, p = 0.001). In birth certificate data, GH was lower in mothers of gastroschisis cases compared to all others (22/927 [2.4%] vs. 144 521/3 428 571 [4.2%], p = 0.005). Adjustment for covariates and simulated BMI also showed a lower prevalence of GH in mothers of gastroschisis cases (OR = 0.58, 95% CI = 0.35–0.94, p = 0.005). Conclusion: Women delivering a live-born infant with gastroschisis may have a decreased prevalence of GH. This unique observation warrants additional confirmatory studies. Such studies might provide insight into both GH and gastroschisis.
Neonatal morbidity in preterm infants after preterm premature rupture of membranes
Authors: Siebert S. , Jakob M. , Gembruch U. , Bartmann P. , Heep A.
Published: December 2019

Objective: To assess neonatal mortality and morbidity after preterm premature rupture of membranes (PPROM) before 24 weeks of gestation. Study design: Retrospective study including live born infants with PPROM before 24 weeks of gestation born at Bonn University Hospital 1994–2002 with a gestational age <23 ± 2 weeks. Results: 69 neonates with PPROM at a median gestational age of 21 weeks were studied. Median latency period to delivery was 53 days, median gestational age at delivery was 27 ± 4 weeks. Overall postnatal survival was 72.5%. In 30.4% chorioamnionitis was diagnosed at birth. 44.9% developed primary sepsis. 69.6% showed respiratory distress syndrome, 14.5% had lung hypoplasia. In 34% of neonates surviving the first month, bronchopulmonary dyplasia was diagnosed. Intraventricular hemorrhage of all grades appeared in 37.7%. Rates of necrotizing enterocolitis (7.2%) and joint contractions (11.6%) were low. Conclusion: Rates of chorioamnionitis, pulmonary and cerebral complications were high in children with PPROM before 24 weeks of gestation.