Asymptomatic neonatal herpes simplex virus infection in mice leads to long-term cognitive impairment.

Neonatal herpes simplex virus (nHSV) is a devastating infection impacting approximately 14,000 newborns globally each year. Infection is associated with high neurologic morbidity and mortality, making early intervention and treatment critical. Clinical outcomes of symptomatic nHSV infections are well-studied, but little is known about the frequency of, or outcomes following, sub-clinical or asymptomatic nHSV. Given the ubiquitous nature of HSV infection and frequency of asymptomatic shedding in adults, subclinical infections are underreported, yet could contribute to long-term neurological damage. To assess potential neurological morbidity associated with subclinical nHSV infection, we developed a low-dose (100 PFU) HSV infection protocol in neonatal C57BL/6 mice. At this dose, HSV DNA was detected in the brain by PCR but was not associated with acute clinical symptoms. However, months after initial inoculation with 100 PFU of HSV, we observed impaired mouse performance on a range of cognitive and memory performance tasks. Memory impairment was induced by infection with either HSV-1 or HSV-2 wild-type viruses, but not by a viral mutant lacking the autophagy-modulating Beclin-binding domain of the neurovirulence gene γ34.5. Retroviral expression of wild type γ34.5 gene led to behavioral pathology in mice, suggesting that γ34.5 expression may be sufficient to cause cognitive impairment. Maternal immunization and HSV-specific antibody treatment prevented offspring from developing neurological sequelae following nHSV-1 infection. Altogether, these results support the idea that subclinical neonatal infections may lead to cognitive decline in adulthood, with possible profound implications for research on human neurodegenerative disorders such as Alzheimer's Disease.

Diagnostic accuracy of prenatal ultrasound in coarctation of aorta: systematic review and individual participant data meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of prenatal ultrasound in detecting coarctation of the aorta (CoA). METHODS: An individual participant data meta-analysis was performed to report on the strength of association and diagnostic accuracy of different ultrasound signs in detecting CoA prenatally. MEDLINE, EMBASE and CINAHL were searched for studies published between January 2000 and November 2021. Inclusion criteria were fetuses with suspected isolated CoA, defined as ventricular and/or great vessel disproportion with right dominance on ultrasound assessment. Individual participant-level data were obtained by two leading teams. PRISMA-IPD and PRISMA-DTA guidelines were used for extracting data, and the QUADAS-2 tool was used for assessing quality and applicability. The reference standard was CoA, defined as narrowing of the aortic arch, diagnosed after birth. The most commonly evaluated parameters on ultrasound, both in B-mode and on Doppler, constituted the index test. Summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and likelihood ratios were computed using the hierarchical summary receiver-operating-characteristics model. RESULTS: The initial search yielded 72 studies, of which 25 met the inclusion criteria. Seventeen studies (640 fetuses) were included. On random-effects logistic regression analysis, tricuspid valve/mitral valve diameter ratio > 1.4 and > 1.6, aortic isthmus/arterial duct diameter ratio < 0.7, hypoplastic aortic arch (all P < 0.001), aortic isthmus diameter Z-score of < -2 in the sagittal (P = 0.003) and three-vessel-and-trachea (P < 0.001) views, pulmonary artery/ascending aorta diameter ratio > 1.4 (P = 0.048) and bidirectional flow at the foramen ovale (P = 0.012) were independently associated with CoA. Redundant foramen ovale was inversely associated with CoA (P = 0.037). Regarding diagnostic accuracy, tricuspid valve/mitral valve diameter ratio > 1.4 had a sensitivity of 72.6% (95% CI, 48.2-88.3%), specificity of 65.4% (95% CI, 46.9-80.2%) and DOR of 5.02 (95% CI, 1.82-13.9). The sensitivity and specificity values were, respectively, 75.0% (95% CI, 61.1-86.0%) and 39.7% (95% CI, 27.0-53.4%) for pulmonary artery/ascending aorta diameter ratio > 1.4, 47.8% (95% CI, 14.6-83.0%) and 87.6% (95% CI, 27.3-99.3%) for aortic isthmus diameter Z-score of < -2 in the sagittal view and 74.1% (95% CI, 58.0-85.6%) and 62.0% (95% CI, 41.6-78.9%) for aortic isthmus diameter Z-score of < -2 in the three-vessel-and-trachea view. Hypoplastic aortic arch had a sensitivity of 70.0% (95% CI, 42.0-88.6%), specificity of 91.3% (95% CI, 78.6-96.8%) and DOR of 24.9 (95% CI, 6.18-100). The diagnostic yield of prenatal ultrasound in detecting CoA did not change significantly when considering multiple categorical parameters. Five of the 11 evaluated continuous parameters were independently associated with CoA (all P < 0.001) but all had low-to-moderate diagnostic yield. CONCLUSIONS: Several prenatal ultrasound parameters are associated with an increased risk for postnatal CoA. However, diagnostic accuracy is only moderate, even when combinations of parameters are considered. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Effect of RMGI Roughness and Dentin Bonding Primer on Shear Bond Strength of Sandwich-type Restorations.

BACKGROUND: The open sandwich technique is a reliable alternative to amalgam placement in deep proximal box preparations, where proper isolation and enamel bonding may not be possible. It is often difficult to prepare the box for composite placement without affecting the resin-modified glass ionomer (RMGI) that has been placed in the gingival portion. We hypothesized that RMGI surfaces that are roughened or those that use all steps in the manufacturing bonding protocol, including the priming solution, applied before placing a bonded composite increment, would have greater composite/RMGI shear bond strength. DESIGN AND METHODS: Shear bond strengths (SBS) of RMGI tested in the presence and absence of SiC roughening and primer-coating were tested using a fourth-generation dentin bonding agent to composite after thermocycling. Twenty specimens for four test conditions were fabricated and investigated. Data were subjected to a two-way ANOVA and the Holm-Sidak post-hoc test. RESULTS: Placing dentin primer on unabraded RMGI provided a statistically significant improvement in SBS, but only modestly. Furthermore, because bond failure consistently occurred within the RMGI itself, none of the surface modifications have a clinically relevant impact on SBS at the RMGI to the composite interface. CONCLUSIONS: Clinicians should be aware that they need not avoid RMGI abrasion and do not need to incorporate all components of a fourth-generation bonding system when covering an RMGI sandwich layer with composite.

Neurologic Outcomes After Radiation Therapy for Severe Spinal Cord Compression in Multiple Myeloma: A Study of 162 Patients.

BACKGROUND: Bone destruction is the most frequent disease-defining clinical feature of multiple myeloma (MM), resulting in skeletal-related events such as back pain, pathological fractures, or neurologic compromise including epidural spinal cord compression (ESCC). Up to 24% of patients with MM will be affected by ESCC. Radiation therapy has been proven to be highly effective in pain relief in patients with MM. However, a critical knowledge gap remains with regard to neurologic outcomes in patients with high-grade ESCC treated with radiation. METHODS: We retrospectively included 162 patients with MM and high-grade ESCC (grade 2 or 3) who underwent radiation therapy of the spine between January 2010 and July 2021. The primary outcome was the American Spinal Injury Association (ASIA) score after 12 to 24 months, or the last known ASIA score if the patient had had a repeat treatment or died. Multivariable logistic regression was used to assess factors associated with poor neurologic outcomes after radiation, defined as neurologic deterioration or lack of improvement. RESULTS: After radiation therapy, 34 patients (21%) had no improvement in their impaired neurologic function and 27 (17%) deteriorated neurologically. Thirty-six patients (22%) underwent either surgery or repeat irradiation after the initial radiation therapy. There were 100 patients who were neurologically intact at baseline (ASIA score of E), of whom 16 (16%) had neurologic deterioration. Four variables were independently associated with poor neurologic outcomes: baseline ASIA (odds ratio [OR] = 6.50; 95% confidence interval [CI] = 2.70 to 17.38; p < 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (OR = 6.19; 95% CI = 1.49 to 29.49; p = 0.015), number of levels affected by ESCC (OR = 4.02; 95% CI = 1.19 to 14.18; p = 0.026), and receiving steroids prior to radiation (OR = 4.42; 95% CI = 1.41 to 16.10; p = 0.015). CONCLUSIONS: Our study showed that 38% of patients deteriorated or did not improve neurologically after radiation therapy for high-grade ESCC. The results highlight the need for multidisciplinary input and efforts in the treatment of high-grade ESCC in patients with MM. Future studies will help to improve patient selection for specific and standardized treatments and to clearly delineate which patients are likely to benefit from radiation therapy. LEVEL OF EVIDENCE: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Accumulation of resveratrol, ferulic acid and iron in seeds confer iron deficiency chlorosis tolerance to a novel genetic stock of peanut (Arachis hypogaea L.) grown in calcareous soils.

Peanut is mostly grown in calcareous soils with high pH which are deficient in available iron (Fe2+) for plant uptake causing iron deficiency chlorosis (IDC). The most pertinent solution is to identify efficient genotypes showing tolerance to limited Fe availability in the soil. A field screening of 40 advanced breeding lines of peanut using NRCG 7472 and ICGV 86031 as IDC susceptible and tolerant checks, respectively, was envisaged for four years. PBS 22040 and 29,192 exhibited maximum tolerance while PBS 12215 and 12,185 were most susceptible. PBS 22040 accumulated maximum seed resveratrol (5.8 ± 0.08 ppm), ferulic acid (378.6 ± 0.31 ppm) and Fe (45.59 ± 0.41 ppm) content. Enhanced chlorophyll retention (8.72-9.50 µg ml-1), carotenoid accumulation (1.96-2.08 µg ml-1), and antioxidant enzyme activity (APX: 35.9-103.9%; POX: 51- 145%) reduced the MDA accumulation (5.61-9.11 µM cm-1) in tolerant lines. The overexpression of Fe transporters IRT1, ZIP5, YSL3 was recorded to the tune of 2.3-9.54; 1.45-3.7; 2.20-2.32- folds respectively in PBS 22040 and 29,192, over NRCG 7472. PBS 22040 recorded the maximum pod yield (282 ± 4.6 g/row), hundred kernel weight (55 ± 0.7 g) and number of pods per three plants (54 ± 1.7). The study thus reports new insights into the roles of resveratrol, ferulic acid and differential antioxidant enzyme activities in imparting IDC tolerance. PBS 22040, being the best performing line, can be the potent source of IDC tolerance for introgression in high yielding but susceptible genotypes under similar edaphic conditions. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01321-9.

Temporal dysregulation of genes in lamb testis cell during sheeppox virus infection.

The present study was aimed to elucidate the host-virus interactions using RNA-Seq analysis at 1 h and 8 h of post-infection of sheeppox virus (SPPV) in lamb testis cell. The differentially expressed genes (DEGs) and the underlying mechanisms linked to the host immune responses were obtained. The protein-protein interaction (PPI) network analysis and ingenuity pathway analysis (IPA) illustrated the interaction between the DEGs and their involvement in cell signalling responses. Highly connected hubs viz. AURKA, CHEK1, CCNB2, CDC6 and MAPK14 were identified through PPI network analysis. IPA analysis showed that IL-6- and ERK5-mediated signalling pathways were highly enriched at both time points. The TP53 gene was identified to be the leading upstream regulator that directly responded to SPPV infection, resulting in downregulation at both time points. The study provides an overview of how the lamb testis genes and their underlying mechanisms link to growth and immune response during SPPV infection.

Acute and sub-acute toxicity study of anti-obesity herbal granules in Sprague Dawley rats.

Toxicological studies are essential for developing novel medications in pharmaceutical industries including ayurvedic preparation. Hence, the present study is aimed to evaluate acute and 28-days repeated dose oral toxicity of anti-obesity polyherbal granules (PHG) in Sprague Dawley rats by OECD guidelines No 425 and 407, respectively. In an acute oral toxicity study, a single dose of 2 g/kg PHG was administered to rats and mortality, body weight, and clinical observations were noted for fourteen days. However, in the subacute oral toxicity study, the PHG was administered orally at doses of 0.3, 0.5 and 1 g/kg daily for 28 days to rats. Food intake and body weight were recorded weekly. On the 29th day, rats were sacrificed and subjected to haematological, biochemical, urine, necropsy, and histopathological analysis. In an acute oral toxicity study, no treatment-related, mortality, behavioral changes, and toxicity were found throughout fourteen days. Likewise, in the sub-acute toxicity study, no mortality and toxic effects were found in haematology, biochemical, urine, necropsy and histopathological analysis in rats for 28 days of treatment with PHG. Based on these results, the LD50 of PHG was found to be greater than 2 g/kg and the no-observed-adverse-effect level (NOAEL) of PHG for rats was found to be 0.5 g/kg/day. Thus, anti-obesity polyherbal granules showed a good safety profile in animal studies and can be considered an important agent for the clinical management of obesity.

Unclassified white matter disorders: A diagnostic journey requiring close collaboration between clinical and laboratory services.

BACKGROUND: Next generation sequencing studies have revealed an ever-increasing number of causes for genetic disorders of central nervous system white matter. A substantial number of disorders are identifiable from their specific pattern of biochemical and/or imaging findings for which single gene testing may be indicated. Beyond this group, the causes of genetic white matter disorders are unclear and a broader approach to genomic testing is recommended. AIM: This study aimed to identify the genetic causes for a group of individuals with unclassified white matter disorders with suspected genetic aetiology and highlight the investigations required when the initial testing is non-diagnostic. METHODS: Twenty-six individuals from 22 families with unclassified white matter disorders underwent deep phenotyping and genome sequencing performed on trio, or larger, family groups. Functional studies and transcriptomics were used to resolve variants of uncertain significance with potential clinical relevance. RESULTS: Causative or candidate variants were identified in 15/22 (68.2%) families. Six of the 15 implicated genes had been previously associated with white matter disease (COL4A1, NDUFV1, SLC17A5, TUBB4A, BOLA3, DARS2). Patients with variants in the latter two presented with an atypical phenotype. The other nine genes had not been specifically associated with white matter disease at the time of diagnosis and included genes associated with monogenic syndromes, developmental disorders, and developmental and epileptic encephalopathies (STAG2, LSS, FIG4, GLS, PMPCA, SPTBN1, AGO2, SCN2A, SCN8A). Consequently, only 46% of the diagnoses would have been made via a current leukodystrophy gene panel test. DISCUSSION: These results confirm the importance of broad genomic testing for patients with white matter disorders. The high diagnostic yield reflects the integration of deep phenotyping, whole genome sequencing, trio analysis, functional studies, and transcriptomic analyses. CONCLUSIONS: Genetic white matter disorders are genetically and phenotypically heterogeneous. Deep phenotyping together with a range of genomic technologies underpin the identification of causes of unclassified white matter disease. A molecular diagnosis is essential for prognostication, appropriate management, and accurate reproductive counseling.

Variability of retinopathy consequent upon novel mutations in LAMA1.

PURPOSE: Bi-allelic mutations in LAMA1 (laminin 1) (OMIM # 150320) cause Poretti-Boltshauser Syndrome (PTBHS), a rare non-progressive cerebellar dysplasia disorder with ophthalmic manifestations including oculomotor apraxia, high myopia, and retinal dystrophy. Only 38 variants, nearly all loss of function have been reported. Here, we describe novel LAMA1 variants and detailed retinal manifestations in two unrelated families. METHODS: Whole-genome sequencing was conducted on three siblings of a consanguineous family with myopia and retinal dystrophy and on a child from an unrelated non-consanguineous couple. Clinical evaluation included full ophthalmic examination, detailed colour, autofluorescence retinal imaging, retinal optical coherence tomography (OCT), fluorescein angiography under anesthesia, and pattern and full-field electroretinography. RESULTS: Genetic analysis revealed a novel homozygous LAMA1 frameshift variant, c.1492del p.(Arg498Glyfs *25), in the affected siblings in family 1 and a novel frameshift c.3065del p.(Gly1022Valfs *2) and a deletion spanning exons 17-23 in an unrelated individual in family 2. Two of the three siblings and the unrelated child had oculomotor apraxia in childhood; none of the siblings had symptoms of other neurological dysfunction as adults. All four had myopia. The affected siblings had a qualitatively similar retinopathy of wide-ranging severity. The unrelated patient had a severe abnormality of retinal vascular development, which resulted in vitreous haemorrhage and neovascular glaucoma in the left eye and a rhegmatogenous retinal detachment in the right eye. CONCLUSIONS: This report describes the detailed retinal structural and functional consequences of LAMA1 deficiency in four patients from two families, and these exhibit significant variability with evidence of both retinal dystrophy and abnormal and incomplete retinal vascularisation.

Multimodality imaging in primary hyperparathyroidism.

Institutional variations in parathyroid adenoma localisation are largely dictated by local experience and availability of imaging investigations, with no consensus on the optimal approach. This review evaluates the role of multiple imaging techniques in primary hyperparathyroidism and highlights their advantages and limitations in different clinical contexts. A clinico-radiological review of parathyroid imaging techniques is illustrated with example cases and data from the literature. These include high-resolution ultrasound, 99mTc-sestamibi planar scintigraphy with and without thyroid subtraction techniques, integrated 99mTc-sestamibi single-photon-emission computed tomography (SPECT)/computed tomography (CT), four-dimensional (4D) CT, and other techniques, such as magnetic resonance imaging, integrated 18F-choline/11C-methionine positron-emission tomography (PET)/CT and angiographic selective venous sampling. The crucial role of parathyroid embryological and gross anatomy in informing the surgical approach to parathyroidectomy is discussed. Finally, a systematic approach to imaging is proposed to maximise the accuracy of imaging localisation of parathyroid lesions, which is crucial for optimal patient management.

A novel bicistronic DNA vaccine with enhanced protective immune response against Bacillus anthracis through DNA prime-protein boost vaccination approach.

Anthrax, by Bacillus anthracis, remains a dreadful fatal hazard worldwide. The currently used anthrax vaccines are plagued by numerous issues that limit their widespread use. As an immunization approach targeting both extracellular antigens and toxins of B. anthracis may achieve better sterile immunity, the present investigation designed a bicistronic secretory anti-anthrax DNA vaccine targeting immune response against toxin and cells. The efficacy of the vaccine was compared with monocistronic DNA vaccines and the currently used anthrax vaccine. For this, mice were immunized with the developed vaccine containing pag (encoding protective antigen to block toxin) and eag genes (encoding EA1 to target cells) of B. anthracis through DNA-prime/Protein-boost (D/P) and DNA prime/DNA-boost (D/D) approaches. There was a >2 and > 5 fold increase in specific antibody level by D/D and D/P approaches respectively, on 42nd days post-immunization (dpi). Serum cytokine profiling showed that both Th1 and Th2 immune responses were elicited, with more Th2 responses in D/P strategy. More importantly, challenge with 100 times LD50 of B. anthracis at 42nd dpi exhibited maximum cumulative survival (83.33 %) by bicistronic D/P approach. Remarkably, immunization with EA1 delayed mortality onset in infection. The study forms the first report on complement-dependent bactericidal activity of antiEA1 antibodies. In short, co-immunization of PA and EA1 through the developed bicistronic DNA vaccine would be an effective immunization approach in anthrax vaccination. Further, D/P strategy could enhance vaccine-induced immunity against B. anthracis. Altogether, the study generates certain critical insights having direct applications in next-generation vaccine development against anthrax.

Baseline PET/CT imaging parameters for prediction of treatment outcome in Hodgkin and diffuse large B cell lymphoma: a systematic review.

PURPOSE: To systematically review the literature evaluating clinical utility of imaging metrics derived from baseline fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) for prediction of progression-free (PFS) and overall survival (OS) in patients with classical Hodgkin lymphoma (HL) and diffuse large B cell lymphoma (DLBCL). METHODS: A search of MEDLINE/PubMed, Web of Science, Cochrane, Scopus and clinicaltrials.gov databases was undertaken for articles evaluating PET/CT imaging metrics as outcome predictors in HL and DLBCL. PRISMA guidelines were followed. Risk of bias was assessed using the Quality in Prognosis Studies (QUIPS) tool. RESULTS: Forty-one articles were included (31 DLBCL, 10 HL). Significant predictive ability was reported in 5/20 DLBCL studies assessing SUVmax (PFS: HR 0.13-7.35, OS: HR 0.83-11.23), 17/19 assessing metabolic tumour volume (MTV) (PFS: HR 2.09-11.20, OS: HR 2.40-10.32) and 10/13 assessing total lesion glycolysis (TLG) (PFS: HR 1.078-11.21, OS: HR 2.40-4.82). Significant predictive ability was reported in 1/4 HL studies assessing SUVmax (HR not reported), 6/8 assessing MTV (PFS: HR 1.2-10.71, OS: HR 1.00-13.20) and 2/3 assessing TLG (HR not reported). There are 7/41 studies assessing the use of radiomics (4 DLBCL, 2 HL); 5/41 studies had internal validation and 2/41 included external validation. All studies had overall moderate or high risk of bias. CONCLUSION: Most studies are retrospective, underpowered, heterogenous in their methodology and lack external validation of described models. Further work in protocol harmonisation, automated segmentation techniques and optimum performance cut-off is required to develop robust methodologies amenable for clinical utility.

In Silico Analysis, Synthesis, and Biological Evaluation of Triazole Derivatives as H1 Receptor Antagonist.

INTRODUCTION: Histamine, a biological amine, is considered as a principal mediator of many pathological processes regulating several essential events in allergies and autoimmune diseases. Numerous derivatives have been developed that strive with histamine at the H1 receptor and prevent binding of histamine at the H1 receptor, thereby preventing allergic reactions. Molecules containing a triazole ring fused with six-membered ring systems are found to possess broad applications in the field of medicine and industry. The present study is an attempt to characterize the impact of the nature of the substituent introduced at 5 positions of the-4H-1,2,4-triazole-3-thiol on their capacities to bind with the H1 receptor. METHODS: Molecular docking (PDB ID: 3RZE) revealed that synthesized derivatives and target proteins were actively involved in binding with Tyr-108, Thr-112, Ala-216, and Phe-432 subunits. A pharmacophore model, new 5-(4-substituted phenyl)-4-(phenylamino)-4-H-1,2,4-triazole-3- thiols (5a-5h) were designed and evaluated for H1-blocking activity using isolated segments from the guinea pig ileum. RESULTS: According to in silico analysis, all the compounds have a topological polar surface area (TPSA) less than 140 Å squared, so they tend to easily penetrate cell membranes. The results show that most of the compounds are non-inhibitors of CYP450 substrates that play a fundamental role in drug metabolism. Compounds 5d (50.53±12.03), 5h (50.62±12.33) and 7a (55.07±12.41) are more active than others. CONCLUSION: Finally, these derivatives were screened for H1 receptor antagonist activity using guinea pig ileum, taking chlorpheniramine maleate as a standard. Most of the compounds were found to possess better antihistamine activity.

Initial clinical experience with a powered circular stapler for colorectal anastomosis.

BACKGROUND: The Echelon circular™ powered stapler (ECP stapler) obviates the need for manual firing of conventional circular staplers during the construction of a colorectal anastomosis, but has not been evaluated clinically. The aim of this study was to perform a clinical evaluation of this stapler. METHODS: A retrospective review of the initial clinical experience of a single surgeon using the ECP stapler for left-sided colorectal anastomosis construction during elective colorectal resections for benign and malignant disease was conducted by analyzing results from a prospectively maintained study database. Additionally, four attending colorectal and/or general surgeons who had performed ≥ 5 colorectal operations with the ECP stapler were invited to complete an anonymous online survey to subjectively assess the user experience with the device. Statistical analysis was conducted using Microsoft Excel Version 15.33. RESULTS: Seventeen patients underwent left-sided anastomotic reconstruction using the ECP stapler. All donuts (proximal and distal) were intact. Anastomotic integrity was evaluated using the air-leak test utilizing flexible video sigmoidoscopy. No leaks were observed, although one patient (5.9%) developed a postoperative pelvic abscess. The anonymous survey was completed by all four surgeons. Subjective evaluation of the ECP stapler suggests that the overall stapling quality, overall device ease-of-use, and the overall perception of anastomotic quality as above average when compared to manual 'end-to-end anastomosis' (EEA) stapling devices. CONCLUSIONS: In an initial clinical evaluation of the ECP stapler, the safety and ease-of-use of the device appears to be satisfactory. Powered stapling and the design of '3D stapling' may provide advantages over manual systems, and may improve the construction quality of left-sided colorectal anastomosis.

The efficacy of endoscopic third ventriculostomy in children 1 year of age or younger: A systematic review and meta-analysis.

PURPOSE: Hydrocephalus is a major cause of morbidity in the pediatric population, with potentially severe consequences if left untreated. Two viable strategies for management of non-communicating hydrocephalus are endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunting. However, there is uncertainty over the safety and efficacy of ETV in younger infants aged 1 year or below. In this systematic review, we aim to elucidate the success rate and procedural risks of ETV in this age group. METHODS: A multi-database (PubMed, Embase, Web of Science) literature search between January 1990 and April 2018 was performed in accordance with PRISMA guidelines. Eligible studies were included if they (i) examined non-communicating hydrocephalus; (ii) quantified the success/failure rates of ETV; and (iii) assessed outcomes in children 1 year of age or younger. RESULTS: A total of 19 articles with 399 patients were eligible for inclusion. Mean age at procedure was 4.2 months (range 34 weeks gestation to 12 months), with 116 females and 143 males. Commonest underlying aetiology was congenital aqueductal stenosis (AS) (60.4%). Remaining causes included post-haemorrhagic, post-infection, Chiari malformations, malignancies and others. Overall and AS mean success rates were 51.6% and 56.5% respectively. Overall complication rate was 10.0%, consisting mainly of CSF leak, infection, and haemorrhage. Younger age was significantly associated with poorer ETV success rate when divided into <6 months and 6-12 months of age (44.4 vs 66.7%; p = 0.0007). Underlying pathology had no significant association with ETV outcome when divided into AS and other pathologies (p = 0.53). CONCLUSIONS: Age is significantly associated with ETV success rates. Pathology-dependent effects were not found in this age group. Despite a lower ETV success rate at younger ages (44.4 vs 66.7%), it offers a comparable safety profile that is independent of age. ETV remains a viable treatment option for non-communicating hydrocephalus for infants aged 1 year or younger.

Patient advice regarding participation in sport in children with disorders of cerebrospinal fluid (CSF) circulation: a national survey of British paediatric neurosurgeons.

BACKGROUND: Management of children with disorders of cerebrospinal fluid (CSF) circulation is a common aspect of paediatric neurosurgical practice. Sport and physical activity play an integral role in the lives of patients in this age group. However, there is little evidence to support the dissemination of appropriate advice to children regarding such activities. The aim of this study was to evaluate the perspectives of clinicians across the UK regarding the participation of children with disorders of CSF circulation in sports. METHODS: Questionnaires were distributed to Consultant Paediatric Neurosurgeons practising across the UK via the Society of British Neurological Surgeons (SBNS). Five different patient scenarios were supplied, and participants were asked to choose whether they would advise participation in the following sports: Taekwondo, rugby, skiing, and football. RESULTS: An overall response rate of 66.7% (36 out of 54 paediatric neurosurgeons) was achieved. The following percentages of clinicians advocated football, rugby, Taekwondo, and skiing across all scenarios: 96%, 75%, 77%, and 97%, respectively. The majority of responders (91.2%) relied on personal experience when providing advice, whilst 50% used available literature and 19.4% used available guidelines. CONCLUSIONS: There is a paucity of evidence in the literature to support the dissemination of appropriate advice to children with disorders of CSF circulation regarding participation in sports. Our findings demonstrate that the majority of clinicians rely on personal experience to make such decisions, emphasizing the necessity of larger scale studies to inform evidence-based guidelines.

A repeating fast radio burst source localized to a nearby spiral galaxy.

Fast radio bursts (FRBs) are brief, bright, extragalactic radio flashes1,2. Their physical origin remains unknown, but dozens of possible models have been postulated3. Some FRB sources exhibit repeat bursts4-7. Although over a hundred FRB sources have been discovered8, only four have been localized and associated with a host galaxy9-12, and just one of these four is known to emit repeating FRBs9. The properties of the host galaxies, and the local environments of FRBs, could provide important clues about their physical origins. The first known repeating FRB, however, was localized to a low-metallicity, irregular dwarf galaxy, and the apparently non-repeating sources were localized to higher-metallicity, massive elliptical or star-forming galaxies, suggesting that perhaps the repeating and apparently non-repeating sources could have distinct physical origins. Here we report the precise localization of a second repeating FRB source6, FRB 180916.J0158+65, to a star-forming region in a nearby (redshift 0.0337 ± 0.0002) massive spiral galaxy, whose properties and proximity distinguish it from all known hosts. The lack of both a comparably luminous persistent radio counterpart and a high Faraday rotation measure6 further distinguish the local environment of FRB 180916.J0158+65 from that of the single previously localized repeating FRB source, FRB 121102. This suggests that repeating FRBs may have a wide range of luminosities, and originate from diverse host galaxies and local environments.

Protocol-driven multidetector SPECT/CT: integration of hybrid imaging into the routine workflow of whole-body bone scintigraphy in oncology patients.

AIM: To analyse the additional clinical value of protocol-driven and selective use of multidetector single-photon-emission tomography/computed tomography (SPECT/CT) in oncology patients undergoing whole-body bone scintigraphy (BS) and to analyse reporter confidence in diagnosis with and without SPECT/CT. MATERIALS AND METHODS: During a 2-year period, 2,954 whole-body BS examinations were performed in oncology patients, with 444 (15%) undergoing additional protocol-driven SPECT/CT. Retrospective evaluation of planar BS and SPECT/CT images was performed by two experienced dual-trained nuclear medicine radiologists. The BS and SPECT/CT images were graded blindly using a five-point scale designed to evaluate the likelihood of a lesion being benign or malignant. Interpretation was applied on a per-patient basis. RESULTS: There was a 74.5% increase in definitive diagnostic classification and a 26.6% reduction in equivocal findings with SPECT/CT when compared to BS alone (p<0001). Of cases initially classified as "probably benign" on BS, 5.1% (10/193) were reclassified to "probably malignant" (1%) or "malignant" (4.1%) using the SPECT/CT data. The highest impact in reporter confidence was seen with SPECT/CT in the interpretation of lesions within the pelvis (34%), ribs (23%), lumbar spine (22%), and thoracic spine (21%). CONCLUSION: Protocol-driven, selective use of SPECT/CT imaging to augment planar BS reduces equivocal findings and improves reporter confidence whilst minimising the impact on patient and reporting workflows.