Radiopaque marker colonic transit study in the pediatric population BSPGHAN Motility Working Group consensus statement.

Functional constipation (FC) is a common condition in childhood in the United Kingdom and worldwide. Various radiological approaches have been established for diagnostic purposes. The radiopaque marker study (ROMS) is universally accepted and used to assess colonic transit time (CTT) in children with FC. Despite being widely used, there is a lack of standardization with various technical protocols, reproducibility of different populations, the purpose for using investigation, variance in the number of markers used, the amount of study days and calculations, the need to empty the colon before performing the test, and whether to perform on medication or off, or the use of specific diets. As part of the British Society of Paediatric Gastroenterology, Hepatology and Nutrition (BSPGHAN) motility working group (MWG), we decided to explore further into the evidence, in order to provide guidance regarding the use of ROMS in dealing with FC in the pediatric population.

Extradural hematoma from trauma to midline skull tumour.

We present a case of extradural hematoma resulting from a relatively minor closed injury over the vertex where a plasma cell tumour had invaded the superior sagittal sinus. The patient underwent an emergency craniotomy and evacuation of the hematoma. Hemostasis and prevention of recollection of the hematoma were hampered by the erosion of the sagittal sinus making its direct repair impossible. This was achieved by hitching up the dura lateral to the sinus to become its lateral wall reinforced by hemostatic agents. The patient made a full recovery. Malignant tumours invading the dural venous sinuses and eroding the skull can cause life-threatening intracranial bleeding after relatively minor trauma.

Biological evaluation of complexes of cyclopentadienyl M(CO)3+ (M = Re, 99mTc) with high blood-brain barrier penetration potential as brain cancer agents.

To address the major medical need for effective chemotherapeutics/diagnostics for brain cancer, in this work three cyclopentadienyl M(CO)3+ (M = Re, 99mTc) complexes, which cross the blood-brain barrier (BBB) in high % and are designed to mimic the anticancer agent 2-phenylbenzothiazole, are in vitro and in vivo evaluated for anticancer action. The study includes cytotoxicity and uptake studies in cancer and healthy neuronal cell lines, mechanistic investigation of potential anticancer pathways, and biodistribution studies in mice bearing glioblastoma xenografts. The stable Re complexes exhibit selective uptake and significant antiproliferative effect, particularly against U-251 MG glioblastoma cells, with no significant toxicity in healthy neurons, demonstrating the suitability of this type of complexes to serve as selective therapeutic/imaging agents for brain cancer. Furthermore, they result in the generation of elevated Reactive Oxygen Species (ROS) levels, and lead to significant G2/M arrest followed by apoptosis. Biodistribution studies in U-251 MG xenograft bearing mice with the radioactive 99mTc complex that exhibits the highest BBB penetration, show retention at the tumor-site offering a diagnostic prospect and, in addition, indicating the capability of the Re analogue to accumulate at the tumor site for therapeutic action. Overall, the complexes demonstrate significant anticancer properties that, combined with their high BBB penetration potential, render them strong candidates for further evaluation as brain cancer agents.

Bisphosphonates as Supplement to Dental Treatment: A Network Meta-Analysis.

The objective of this study was to assess clinical measurements related to the effectiveness of bisphosphonate (BP) administration as a supplement to conventional dental treatment in patients free of bone-related diseases using a network meta-analysis. Only randomized controlled trials (RCTs) were included that provided dental clinical measurements on human patients treated with BPs with or without similar untreated controls or treated with placebo. Information sources included a systematic search of 17 electronic databases up to August 2020, complemented by manual searches. Risk of bias assessment was performed with the revised Cochrane risk of bias tool for randomized trials (RoB 2.0). Extracted measurements were pooled according to time of evaluation. The random-effects model by DerSimonian and Laird was used to calculate mean differences (MDs) and the respective 95% confidence intervals (CIs). Seven RCTs were included in the network meta-analysis, assessing 391 subjects reporting on periodontal treatment effects after 2 to 12 mo of BP administration. BP treatment was associated with significant improvement of most clinical measurements, compared with BP-naive controls. According to the network ranking, alendronate was more efficient in improvement of probing depth and clinical attachment gain when compared to zoledronate or alendronate/risedronate. Similarly, the local application of alendronate as a gel was more effective than the oral administration. A long-term analysis of the pharmaceutical effects was not possible due to insufficient data. The current review, performed according to existing guidelines, included only RCTs and, through appropriate statistical analyses, provided precise estimates for most assessed outcomes. However, no adverse effects or long-term treatment results were analyzed due to inadequate pertinent data. BP administration seems to be beneficial in the short term for the treatment of periodontal diseases, mainly through controlling periodontal inflammation.

Child perceptions questionnaire: translation, cultural adaptation and initial validation in a Greek adolescent population with malocclusion.

PURPOSE: Several studies have shown that orthodontic anomalies may affect young people's Oral Health-Related Quality of Life (OHRQoL). The purpose the present study was to translate in the Greek language, culturally adapt and initially validate the CPQ11-14 ISF-16 for a Greek adolescent population with malocclusion. METHODS: Following relevant methodological recommendations, after translation, the comprehensiveness of the Greek version of CPQ11-14 ISF-16 (CPQ11-14 ISF-16-GR) was verified in a pilot study of 20 Greek adolescents. The main study was undertaken in a sample of 200 adolescents that presented for an initial consultation at the Postgraduate Orthodontic Clinic. Cronbach's alpha was used to test internal consistency/reliability and Spearman's rho for criterion validity with the Oral Health Impact Profile (OHIP-14). Forty individuals completed the same questionnaires again after 3 weeks. Test-retest reliability was assessed using Intraclass Correlation Coefficient. Statistical tests were undertaken using SPSS (v. 24, IBM Corp., NY, USA). RESULTS: The CPQ11-14 ISF-16-GR presented high internal consistency (Cronbach's alpha = 0.848 > 0.70) and very satisfactory Discrimination Index (DI = 0.47 > 0.30). Moreover, the CPQ11-14ISF-16 showed excellent criterion validity with OHIP-14 (rho = 0.719, p < 0.001). Test-retest reliability was at high levels as well (ICC = 0.719, p < 0.001). CONCLUSION: The CPQ11-14 ISF-16-GR exhibits satisfactory psychometric properties to continue the investigation of OHRQoL in Greek adolescents with malocclusion. Further testing of is required in a variety of environments to increase generalizability and investigate the particular characteristics of CPQ application in malocclusion cases.

Paediatric endophthalmitis: a UK retrospective study.

INTRODUCTION: Paediatric endophthalmitis is a severe but rare complication of intraocular surgery, penetrating trauma and far less commonly extra-ocular surgery or endogenous origin. We set out to establish the incidence and risk factors of exogenous endophthalmitis in children, and to develop an evidence-based protocol that can be used for treatment of suspected exogenous endophthalmitis in children. METHODS: Microbiology reports and operation numbers were obtained from two large tertiary referral hospitals sharing 24-h paediatric ophthalmology cover for the period January 2009-December 2016. All cases of aqueous and/or vitreous tap performed on children aged ≤18 years were identified and case notes reviewed for complete information on each case. RESULTS: Sixteen cases were eligible for inclusion as 'postoperative endophthalmitis': complete data was found on 13 cases. The incidence of postoperative endophthalmitis was 0.17% over 7 years. The mean age of presentation was 5.5 years (range from 7 months to 16 years and 9 months), from 3 days-78 months post operatively. In all, 11/13 had at least one glaucoma procedure. Microbiology results showed growth in 8/13. Most isolates were Gram-positive bacteria but Gram-negatives were also isolated and in one case Candida from a conjunctival swab. The antibiotic regime varied depending on age, organism identified and sensitivities. In all, 9/13 had hand movement or worse vision after treatment. CONCLUSION: Paediatric endophthalmitis may present to any paediatric/general ophthalmologist. It is a rare but devastating condition with poor visual prognosis, requiring prompt recognition and aggressive management. Previous glaucoma surgery is a long-term risk factor in our local paediatric population. Based on our study, an evidence-based protocol for management is proposed in order to improve outcomes.

Giant central lumbar disc herniations: a case for the transdural approach.

Giant central lumbar disc protrusions can pose a significant operative challenge. Clinically, these patients are at risk of permanent disability, due not only to preoperative neural compromise caused by the protrusion itself but also to the potential iatrogenic risks associated with the standard extradural microdiscectomy technique. This is the first report to date of a giant central L3/4 disc protrusion being successfully treated through a transdural microdiscectomy approach. Prior to this report, there have been just two cases describing its application in the lumbar spine. However, neither of these reports has described its use below the level of L2/3. We compare our surgical technique with these authors and discuss the pros and cons of this surgical approach relative to the standard extradural microdiscectomy technique. Overall, we have observed encouraging results from this approach and this report would support a role for further investigation into this rarely used technique.

Quality of life and functional vision in children treated for cataract-a cross-sectional study.

PurposeChildren with cataract and their families face intensive medical and surgical management, with numerous hospital attendances, topical medications, and surgical procedures, as well as uncertainty about the child's future visual ability, education, and independence. Little is known about the impact on functional visual ability, vision-, and health-related quality of life (VR-, HR-QoL).Patients and methodsSeventy two children aged 2-16 years (mean 8.45, SD 4.1) treated for developmental or secondary cataract and their parents/carers completed three validated instruments measuring functional visual ability, VR-, and HR-QoL: the Cardiff Visual Ability Questionnaire for Children (CVAQC), Impact of Vision Impairment for Children (IVI-C), and PedsQL V 4.0.ResultsAll scores are markedly reduced: median (interquartile range (IQR)) CVAQC score -1.42 (-2.28 to -0.03), mean (SD) IVI-C score 65.67 (16.91), median (IQR) PedsQL family impact score 75 (56.94-88.19), parent report 71.74 (51.98-88.5), self-report 76.09 (61.96-89.13). Psychosocial PedsQL subscores are lower than physical subscores. Parent-completed tools (PedsQL family and parent report) state greater impact on HR-QoL than tools completed by children/young people, particularly in teenagers. Older children/young people have higher functional visual ability scores than younger children.ConclusionsCataract has a marked a long-term impact on functional visual ability and quality of life of children and young people, with HR-QoL affected to degrees reported in children with severe congenital cardiac defects or liver transplants.

No association between seniority of surgeon and postoperative recurrence of chronic subdural haematoma.

INTRODUCTION: Neurosurgical trainees should achieve competency in chronic subdural haematoma (CSDH) drainage at an early stage in training. The effect of surgeon seniority on recurrence following surgical drainage of CSDH was examined. METHODS: All CSDH cases performed at St George's Hospital in London between March 2009 and March 2012 were analysed. Recurrence was defined as clinical deterioration with computed tomography evidence of CSDH requiring reoperation within six months. The following risk factors were considered: seniority of primary and supervising surgeons, timing of surgery (working hours, outside working hours), patient related factors (age, antiplatelets, warfarin) and operative factors (general vs local anaesthesia, burr holes vs craniotomy, drain use). For recurrent cases, we examined the distance of the cranial opening from the thickest part of the CSDH. RESULTS: A total of 239 patients (median age: 79 years, range: 33-98 years) had 275 CSDH drainage operations. The overall recurrence rate was 13.1%. The median time between the initial procedure and reoperation was 16 days (range: 1-161 days). The only statistically significant risk factor for recurrence was antiplatelets (odds ratio: 2.62, 95% confidence interval: 1.13-6.10, p<0.05). Warfarin, grade of surgeon, timing of surgery, type of anaesthesia, type of operation and use of drains were not significant risk factors. In 26% of recurrent CSDH cases, the burr holes or craniotomy flaps were placed with borderline accuracy. CONCLUSIONS: CSDH drainage is a suitable case for neurosurgical trainees to perform without increasing the chance of recurrence.

Reliable but Timesaving: In Search of an Efficient Quantum-chemical Method for the Description of Functional Fullerenes.

Fullerene and its derivatives are currently one of the most intensively investigated species in the area of nanomedicine and nanochemistry. Various unique properties of fullerenes are responsible for their wide range applications in industry, biology and medicine. A large pool of functionalized C60 and C70 fullerenes is investigated theoretically at different levels of quantum-mechanical theory. The semiempirial PM6 method, density functional theory with the B3LYP functional, and correlated ab initio MP2 method are employed to compute the optimized structures, and an array of properties for the considered species. In addition to the calculations for isolated molecules, the results of solution calculations are also reported at the DFT level, using the polarizable continuum model (PCM). Ionization potentials (IPs) and electron affinities (EAs) are computed by means of Koopmans' theorem as well as with the more accurate but computationally expensive ΔSCF method. Both procedures yield comparable values, while comparison of IPs and EAs computed with different quantum-mechanical methods shows surprisingly large differences. Harmonic vibrational frequencies are computed at the PM6 and B3LYP levels of theory and compared with each other. A possible application of the frequencies as 3D descriptors in the EVA (EigenVAlues) method is shown. All the computed data are made available, and may be used to replace experimental data in routine applications where large amounts of data are required, e.g. in structure-activity relationship studies of the toxicity of fullerene derivatives.

Comparative study of interactions of aliskiren and AT1 receptor antagonists with lipid bilayers.

The renin-angiotensin-aldosterone system (RAAS) plays a key role in the regulation of blood pressure. Renin is the rate limiting enzyme of the RAAS and aliskiren is a highly potent and selective inhibitor of the human renin. Renin is known to be active both in the circulating blood stream as well as locally, when bound to the (pro)-renin receptor ((P)RR). In this study we have investigated a possible mechanism of action of aliskiren, in which its accumulation in the plasma membrane is considered as an essential step for effective inhibition. Aliskiren's interactions with model membranes (cholesterol rich and poor) have been investigated by applying different complementary techniques: differential scanning calorimetry (DSC), Raman spectroscopy, magic angle spinning (MAS) nuclear magnetic resonance (NMR) spectroscopy and small- and wide-angle X-ray scattering (SAXS and WAXS). In addition, in silico molecular dynamics (MD) calculations were applied for further confirmation of the experimental data. Aliskiren's thermal effects on the pre- and main transition of dipalmitoyl-phosphatidylcholine (DPPC) membranes as well as its topographical position in the bilayer show striking similarities to those of angiotensin II type 1 receptor (AT1R) antagonists. Moreover, at higher cholesterol concentrations aliskiren gets expelled from the membrane just as it has been recently demonstrated for the angiotensin receptor blocker (ARB) losartan. Thus, we propose that both the AT1R and the (P)RR-bound renin active sites can be efficiently blocked by membrane-bound ARBs and aliskiren when cholesterol rich membrane rafts/caveolae are formed in the vicinity of the receptors.

Ultrasound-guided transoral drainage of a paediatric parapharyngeal abscess.

OBJECTIVE: To report and discuss the surgical use of ultrasonography for draining a parapharyngeal space infection in a child. CASE REPORT: The use of image-guided surgery for draining a parapharyngeal abscess has been previously reported, with computed tomography for an intra-oral approach and ultrasound for an external approach. We present the first case report of a four-year-old child with a retropharyngeal abscess and a deep parapharyngeal abscess in whom neck ultrasound was used to assist intra-oral drainage. CONCLUSION: Neck ultrasound may be used in paediatric patients to visualise access to the parapharyngeal space through the intra-oral route for abscess drainage.

Childhood glaucoma surgery in the 21st century.

Most children with glaucoma will require surgery in their lifetime, often in their childhood years. The surgical management of childhood glaucoma is however challenging, largely because of its greater potential for failure and complications as compared with surgery in adults. The available surgical repertoire for childhood glaucoma has remained relatively unchanged for many years with most progress owing to modifications to existing surgery. Although the surgical approach to childhood glaucoma varies around the world, angle surgery remains the preferred initial surgery for primary congenital glaucoma and a major advance has been the concept of incising the whole of the angle (circumferential trabeculotomy). Simple modifications to the trabeculectomy technique have been shown to considerably minimise complications. Glaucoma drainage devices maintain a vital role for certain types of glaucoma including those refractory to other surgery. Cyclodestruction continues to have a role mainly for patients following failed drainage/filtering surgery. Although the prognosis for childhood glaucoma has improved significantly since the introduction of angle surgery, there is still considerable progress to be made to ensure a sighted lifetime for children with glaucoma all over the world. Collaborative approaches to researching and delivering this care are required, and this paper highlights the need for more high-quality prospective surgical trials in the management of the childhood glaucoma.

Surgical management of acute subdural haematomas: current practice patterns in the United Kingdom and the Republic of Ireland.

INTRODUCTION: Uncertainty remains as to the role of decompressive craniectomy (DC) for primary evacuation of acute subdural haematomas (ASDH). In 2011, a collaborative group was formed in the UK with the aim of answering the following question: "What is the clinical- and cost-effectiveness of decompressive craniectomy, in comparison with craniotomy for adult patients undergoing primary evacuation of an ASDH?" The proposed RESCUE-ASDH trial (Randomised Evaluation of Surgery with Craniectomy for patients Undergoing Evacuation of Acute Subdural Haematoma) is a multicentre, pragmatic, parallel group randomised trial of DC versus craniotomy for adult head-injured patients with an ASDH. In this study, we used an online questionnaire to assess the current practice patterns in the management of ASDH in the UK and the Republic of Ireland, and to gauge neurosurgical opinion regarding the proposed RESCUE-ASDH trial. MATERIALS AND METHODS: A questionnaire survey of full members of the Society of British Neurological Surgeons and members of the British Neurosurgical Trainees Association was undertaken between the beginning of May and the end of July 2012. RESULTS: The online questionnaire was answered by 95 neurosurgeons representing 31 of the 32 neurosurgical units managing adult head-injured patients in the UK and the Republic of Ireland. Forty-five percent of the respondents use primary DC in at least 25% of patients with ASDH. In addition, of the 22 neurosurgical units with at least two Consultant respondents, only three units (14%) showed intradepartmental agreement regarding the proportion of their patients receiving a primary DC for ASDH. CONCLUSION: The survey results demonstrate that there is significant uncertainty as to the optimal surgical technique for primary evacuation of ASDH. The fact that the majority of the respondents are willing to become collaborators in the planned RESCUE-ASDH trial highlights the relevance of this important subject to the neurosurgical community in the UK and Ireland.

Comparative binding effects of aspirin and anti-inflammatory Cu complex in the active site of LOX-1.

(1)H NMR Saturation Transfer Difference (STD) experiments were applied to study the binding of aspirin and of an anti-inflammatory complex of Cu(I), namely [Cu(tpp)(pmt)](2) [pmt = 2-mercaptopyrimidine), synthesized in an attempt to develop novel metallotherapeutic molecules. While aspirin showed only very weak binding, the complex [Cu(tpp)(pmt)](2) clearly favored binding to LOX-1. In silico docking experiments in LOX-1 showed that aspirin does only weakly bind to LOX-1, while the complex binds with high affinity. In addition, docking experiments and molecular dynamics (MD) simulations showed that the complex binds via hydrogen bonding (HB), to an allosteric site of LOX-1, revealing that this enzyme has more than one accessible site for complex metallotherapeutic molecules. When aspirin was added in the solution containing LOX and the complex [Cu(tpp)(pmt)](2), the former was shown to hinder the binding of the Cu complex significantly. This may be interpreted as the copper complex aiding the transfer of aspirin through an acid-base reaction at the LOX enzyme which subsequently blocks its binding.

Effectiveness of pre-surgical infant orthopedic treatment for cleft lip and palate patients: a systematic review and meta-analysis.

The objective of the study was to systematically summarize current evidence on the effectiveness of pre-surgical infant orthopedics (PSIO) in cleft lip and palate (CLP) patients. Electronic and manual searches were conducted, and using specific inclusion and exclusion criteria, data extraction and analysis was performed by two independent investigators. When possible, overall pooled estimates with 95% confidence intervals were obtained using the random-effects model. Twenty-four of 885 original studies met the inclusion criteria and were included in the qualitative synthesis, whereas 10 of them were included in the quantitative synthesis (meta-analysis). Except for the variable M-T-C(5) assessing maxillary arch form, which presented an increase at 48 months of follow-up, all other variables concerning craniofacial and dentoalveolar changes demonstrated no significant differences, indicating that PSIO treatment has no effect on CLP patients. The limited evidence derived from this study does not seem to support the short- or long-term effectiveness of PSIO in CLP patients.

New (99m)Tc(CO)(3) mannosylated dextran bearing S-derivatized cysteine chelator for sentinel lymph node detection.

The aim of the present study is to synthesize new mannosylated dextran derivative that can be labeled with Tc-99m for potential use in sentinel lymph node detection (SLND). The compound was designed to have a dextran with molecular weight of 10 kDa as a backbone, mannose for binding to mannose receptors of the lymph node and S-derivatized cysteine as a suitable chelator for labeling with [(99m)Tc(H(2)O)(3)(CO)(3)](+) precursor. Reaction of allyl bromide with dextran (MW 11800) yielded the intermediate allyl-dextran (1) with about 40% coupling. Addition of cysteine to allyl-dextran resulted in the S-derivatized cysteine, compound DC15 (2). The final product DCM20 (3) was obtained in good yield after in situ hydrolysis and activation of cyanomethyl tetraacetyl-1-thio-d-mannopyranoside and coupling to DC15. All derivatives were purified by ultrafiltration and characterized by NMR. DC15 and DCM20 were quantitatively labeled with (99m)Tc (>95% radiochemical purity) using the fac-[(99m)Tc(OH(2))(3)(CO)(3)](+) precursor and ligand concentration of 1.5 × 10(-6) M at neutral pH. Both (99m)Tc-labeled compounds (99m)Tc(CO)(3)-DC15 (6) and (99m)Tc(CO)(3)-DCM20 (7) remained stable after 6 h incubation at 37 °C in the presence of excess histidine or cysteine, as well as even after 20-fold dilution and incubation for 24 h at room temperature. The characterization of the compounds 6 and 7 was performed by comparing their HPLC radiochromatograms with those of their rhenium surrogates Re(CO)(3)-DC15 (4) and Re(CO)(3)-DCM20 (5) respectively that were prepared using the precursor [NEt(4)](2)fac-[ReBr(3)(CO)(3)] and characterized by IR and NMR spectroscopy. When injected subcutaneously from the foot pad of mice, (99m)Tc-labeled mannosylated dextran (7) showed accumulation in the popliteal lymph node (SLN in this model) higher than that of non-mannosylated analogue (6) and the (99m)Tc-phytate serving as standard. Compound 7 also exhibited lower radioactivity levels at the injection site compared to (99m)Tc-phytate. The SPECT/CT studies in mice confirmed that 7 accumulated in the popliteal lymph node allowing its clear visualization. The present findings demonstrate that compound 7 ((99m)Tc(CO)(3)-DCM20) is promising and merits further evaluation as a radiopharmaceutical for sentinel lymph node detection.