TDP-43 regulates LC3ylation in neural tissue through ATG4B cryptic splicing inhibition.

Amyotrophic lateral sclerosis (ALS) is an adult-onset motor neuron disease with a mean survival time of three years. The 97% of the cases have TDP-43 nuclear depletion and cytoplasmic aggregation in motor neurons. TDP-43 prevents non-conserved cryptic exon splicing in certain genes, maintaining transcript stability, including ATG4B, which is crucial for autophagosome maturation and Microtubule-associated proteins 1A/1B light chain 3B (LC3B) homeostasis. In ALS mice (G93A), Atg4b depletion worsens survival rates and autophagy function. For the first time, we observed an elevation of LC3ylation in the CNS of both ALS patients and atg4b-/- mouse spinal cords. Furthermore, LC3ylation modulates the distribution of ATG3 across membrane compartments. Antisense oligonucleotides (ASOs) targeting cryptic exon restore ATG4B mRNA in TARDBP knockdown cells. We further developed multi-target ASOs targeting TDP-43 binding sequences for a broader effect. Importantly, our ASO based in peptide-PMO conjugates show brain distribution post-IV administration, offering a non-invasive ASO-based treatment avenue for neurodegenerative diseases.

Reconceiving Domestic Burning Controls: Air Quality Alerts, Behavioural Responsive Regulation, and Designing for Compliance.

Domestic combustion emissions pose a growing risk to public health, especially in the UK. Existing responses are polarised, with government advocating use of lower emission fuels and stoves while clean air campaigners call for blanket bans on burning. However, each approach is limited in its ability to control these emissions. An alternative can be found in the U.S.A., where 'burn alert' systems require stove and fireplace users to avoid lighting during periods of actual or projected poor air quality. Given the effectiveness of these regimes, the current study designs and evaluates the effectiveness and acceptability of a burn alert system in the UK for the first time, drawing on the theoretical perspective of behavioural responsive regulation. Fifty participants were recruited to use the system over 2 weeks in winter. The findings illustrate that a voluntary burn alert system can dissuade burning among users. Of those in receipt of an alert, 74% reduced burning frequency or burned for a shorter duration. In total, the alert system prevented at least 178 hours of burning for this group. Qualitative findings show that the consistency of the behavioural response is influenced by technical, structural, and environmental factors, providing key insight into how UK-based burn alert systems could be modified to increase the consistency of compliance in future. The overall conclusion is that burn alerts could be introduced in the UK and beyond, as a means of reducing domestic combustion emissions and their associated public health risks.

Single-cell transcriptomic analysis of retinal immune regulation and blood-retinal barrier function during experimental autoimmune uveitis.

Uveitis is characterised by breakdown of the blood-retinal barrier (BRB), allowing infiltration of immune cells that mediate intraocular inflammation, which can lead to irreversible damage of the neuroretina and the loss of sight. Treatment of uveitis relies heavily on corticosteroids and systemic immunosuppression due to limited understanding of disease pathogenesis. We performed single-cell RNA-sequencing of retinas, as well as bulk RNA-sequencing of retinal pigment epithelial (RPE) cells from mice with experimental autoimmune uveitis (EAU) versus healthy control. This revealed that the Th1/Th17-driven disease induced strong gene expression changes in response to inflammation in rods, cones, Müller glia and RPE. In particular, Müller glia and RPE cells were found to upregulate expression of chemokines, complement factors, leukocyte adhesion molecules and MHC class II, thus highlighting their contributions to immune cell recruitment and antigen presentation at the inner and outer BRB, respectively. Additionally, ligand-receptor interaction analysis with CellPhoneDB revealed key interactions between Müller glia and T cell / natural killer cell subsets via chemokines, galectin-9 to P4HB/TIM-3, PD-L1 to PD-1, and nectin-2/3 to TIGIT signalling axes. Our findings elucidate mechanisms contributing to breakdown of retinal immune privilege during uveitis and identify novel targets for therapeutic interventions.

Papillary tumor of the pineal region: analysis of DNA methylation profiles and clinical outcomes in 76 cases.

Papillary tumor of the pineal region (PTPR) is an uncommon tumor of the pineal region with distinctive histopathologic and molecular characteristics. Experience is limited with respect to its molecular heterogeneity and clinical characteristics. Here, we describe 39 new cases and combine these with 37 previously published cases for a cohort of 76 PTPR's, all confirmed by methylation profiling. As previously reported, two main methylation groups were identified (PTPR-A and PTPR-B). In our analysis we extended the subtyping into three subtypes: PTPR-A, PTPR-B1 and PTPR-B2 supported by DNA methylation profile and genomic copy number variations. Frequent loss of chromosome 3 or 14 was found in PTPR-B1 tumors but not in PTPR-B2. Examination of clinical outcome showed that nearly half (14/30, 47%) of examined patients experienced tumor progression with significant difference among the subtypes (p value = 0.046). Our analysis extends the understanding of this uncommon but distinct neuroepithelial tumor by describing its molecular heterogeneity and clinical outcomes, including its tendency towards tumor recurrence.

Interpretation of Data from Translational Rodent Nerve Injury and Repair Models.

This article highlights the use of rodents as preclinical models to evaluate the management of nerve injuries, describing the pitfalls and value from rodent nerve injury and regeneration outcomes, as well as treatments derived from these rodent models. The anatomic structure, size, and cellular and molecular differences and similarities between rodent and human nerves are summarized. Specific examples of success and failure when assessing outcome metrics are presented for context. Evidence for translation to clinical practice includes the topics of electrical stimulation, Tacrolimus (FK506), and acellular nerve allografts.

An overview of the current diagnostic approach to Periprosthetic Joint Infections.

The diagnosis of periprosthetic joint infections (PJI) presents a formidable challenge to orthopaedic surgeons due to its complex and diverse manifestations. Accurate diagnosis is of utmost importance, as even mild pain following joint replacement surgery may indicate PJI in the absence of a definitive gold standard diagnostic test. Numerous diagnostic modalities have been suggested in the literature, and international societies have continually updated diagnostic criteria for this debilitating complication. This review article aims to comprehensively examine the latest evidence-based approaches for diagnosing PJI. Through a thorough analysis of current literature, we explore promising diagnostic strategies that have demonstrated effectiveness in identifying PJI. These strategies encompass the utilization of laboratory markers, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), alongside imaging techniques such as magnetic resonance imaging (MRI) and leukocyte scintigraphy. Additionally, we highlight the importance of synovial fluid analysis, including the potential role of alpha-defensin as a biomarker, and examine evolving international diagnostic criteria to standardize and improve diagnostic accuracy.

Chemical genetic screens reveal defective lysosomal trafficking as synthetic lethal with NF1 loss.

Neurofibromatosis type 1, a genetic disorder caused by pathogenic germline variations in NF1, predisposes individuals to the development of tumors, including cutaneous and plexiform neurofibromas (CNs and PNs), optic gliomas, astrocytomas, juvenile myelomonocytic leukemia, high-grade gliomas and malignant peripheral nerve sheath tumors (MPNSTs), which are chemotherapy- and radiation-resistant sarcomas with poor survival. Loss of NF1 also occurs in sporadic tumors, such as glioblastoma (GBM), melanoma, breast, ovarian and lung cancers. We performed a high-throughput screen for compounds that were synthetic lethal with NF1 loss, which identified several leads, including the small molecule Y102. Treatment of cells with Y102 perturbed autophagy, mitophagy and lysosome positioning in NF1-deficient cells. A dual proteomics approach identified BLOC-one-related complex (BORC), which is required for lysosome positioning and trafficking, as a potential target of Y102. Knockdown of a BORC subunit using siRNA recapitulated the phenotypes observed with Y102 treatment. Our findings demonstrate that BORC might be a promising therapeutic target for NF1-deficient tumors.

Instrumented Mouthguard Decoupling Affects Measured Head Kinematic Accuracy.

Many recent studies have used boil-and-bite style instrumented mouthguards to measure head kinematics during impact in sports. Instrumented mouthguards promise greater accuracy than their predecessors because of their superior ability to couple directly to the skull. These mouthguards have been validated in the lab and on the field, but little is known about the effects of decoupling during impact. Decoupling can occur for various reasons, such as poor initial fit, wear-and-tear, or excessive impact forces. To understand how decoupling influences measured kinematic error, we fit a boil-and-bite instrumented mouthguard to a 3D-printed dentition mounted to a National Operating Committee on Standards for Athletic Equipment (NOCSAE) headform. We also instrumented the headform with linear accelerometers and angular rate sensors at its center of gravity (CG). We performed a series of pendulum impact tests, varying impactor face and impact direction. We measured linear acceleration and angular velocity, and we calculated angular acceleration from the mouthguard and the headform CG. We created decoupling conditions by varying the gap between the lower jaw and the bottom face of the mouthguard. We tested three gap conditions: 0 mm (control), 1.6 mm, and 4.8 mm. Mouthguard measurements were transformed to the CG and compared to the reference measurements. We found that gap condition, impact duration, and impact direction significantly influenced mouthguard measurement error. Error was higher for larger gaps and in frontal (front and front boss) conditions. Higher errors were also found in padded conditions, but the mouthguards did not collect all rigid impacts due to inherent limitations. We present characteristic decoupling time history curves for each kinematic measurement. Exemplary frequency spectra indicating characteristic decoupling frequencies are also described. Researchers using boil-and-bite instrumented mouthguards should be aware of their limitations when interpreting results and should seek to address decoupling through advanced post-processing techniques when possible.

A comparative analysis of IDH-mutant glioma in pediatric, young adult, and older adult patients.

BACKGROUND: The frequency and significance of IDH mutations in glioma across age groups is incompletely understood. We performed a multi-center retrospective age-stratified comparison of patients with IDH-mutant gliomas to identify age-specific differences in clinico-genomic features, treatments, and outcomes. METHODS: Clinical, histologic, and sequencing data from patients with IDH-mutant, grade 2-4 gliomas, were collected from collaborating institutions between 2013-2019. Patients were categorized as pediatric (<19y), YA (19-39y) or older adult (≥40y). Clinical presentation, treatment, histologic, and molecular features were compared across age categories using Fisher's exact test or analysis-of-variance. Cox proportional-hazards regression was used to determine association of age and other covariates with overall (OS) and progression-free survival (PFS). RESULTS: We identified a cohort of 379 patients (204 YA) with IDH-mutant glioma with clinical data. There were 155 (41%) oligodendrogliomas and 224 (59%) astrocytomas. YA showed significantly shorter PFS and shorter median time-to-malignant transformation (MT) compared to pediatric and adult groups, but no significant OS difference. Adjusting for pathology type, extent of resection, and upfront therapy in multivariable analysis, the YA group was independently prognostic of shorter PFS than pediatric and adult groups. Among astrocytomas, CDK4/6 copy number amplifications were associated with both shorter PFS and shorter OS. Among oligodendrogliomas, PIK3CA and CDKN2A/2B alterations were associated with shorter OS. CONCLUSIONS: IDH-mutant glioma YA patients had significantly shorter PFS and time to MT but did not differ in OS compared to pediatric and adult groups. Treatment approach varied significantly by patient age and warrant further study as addressable age-associated outcome drivers.

Periprosthetic tibial fracture as a complication of unicompartmental knee arthroplasty: Current insights.

Periprosthetic fracture following knee arthroplasty is a rare but devastating complication associated with significant morbidity. With unicompartmental knee arthroplasty being performed far less frequently than total knee arthroplasty, periprosthetic fracture following unicompartmental knee arthroplasty presents a particular challenge to orthopaedic surgeons, due to clinical unfamiliarity and sparsity of literature. An up-to-date review of the epidemiology, risk factors, and management strategies for PPF after UKA is presented.

A RAD18-UBC13-PALB2-RNF168 axis mediates replication fork recovery in BRCA1-deficient cancer cells.

BRCA1/2 proteins function in genome stability by promoting repair of double-stranded DNA breaks through homologous recombination and by protecting stalled replication forks from nucleolytic degradation. In BRCA1/2-deficient cancer cells, extensively degraded replication forks can be rescued through distinct fork recovery mechanisms that also promote cell survival. Here, we identified a novel pathway mediated by the E3 ubiquitin ligase RAD18, the E2-conjugating enzyme UBC13, the recombination factor PALB2, the E3 ubiquitin ligase RNF168 and PCNA ubiquitination that promotes fork recovery in BRCA1- but not BRCA2-deficient cells. We show that this pathway does not promote fork recovery by preventing replication fork reversal and degradation in BRCA1-deficient cells. We propose a mechanism whereby the RAD18-UBC13-PALB2-RNF168 axis facilitates resumption of DNA synthesis by promoting re-annealing of the complementary single-stranded template strands of the extensively degraded forks, thereby allowing re-establishment of a functional replication fork. We also provide preliminary evidence for the potential clinical relevance of this novel fork recovery pathway in BRCA1-mutated cancers, as RAD18 is over-expressed in BRCA1-deficient cancers, and RAD18 loss compromises cell viability in BRCA1-deficient cancer cells.

Isolated Osseous Excision in the Adult Carpus: A Narrative Review.

Various pathologies of the adult carpus result in clinical scenarios where excision can be considered and even recommended. In the appropriate patient population, isolated carpal excision can alleviate pain and improve mobility. Excisions of the pisiform, trapezium, and trapezoid have abundant literature evidence to support positive long-term functional outcomes. In contrast, isolated excision of the capitate, hamate, and triquetrum has limited support in the literature secondary to compromise of carpal mechanics and lead to recurrent pain. Additionally, isolated scaphoid and lunate excision are best avoided secondary to carpal collapse and should be paired with concomitant stabilizing procedures in the carpus. This article provides a comprehensive literature review of isolated excision of each osseous carpal bone, their indications, and previously assessed outcomes.

Scalable purification of extracellular vesicles with high yield and purity using multimodal flowthrough chromatography.

Extracellular vesicles (EVs) are cell derived membranous nanoparticles. EVs are important mediators of cell-cell communication via the transfer of bioactive content and as such they are being investigated for disease diagnostics as biomarkers and for potential therapeutic cargo delivery to recipient cells. However, existing methods for isolating EVs from biological samples suffer from challenges related to co-isolation of unwanted materials such as proteins, nucleic acids, and lipoproteins. In the pursuit of improved EV isolation techniques, we introduce multimodal flowthrough chromatography (MFC) as a scalable alternative to size exclusion chromatography (SEC). The use of MFC offers significant advantages for purifying EVs, resulting in enhanced yields and increased purity with respect to protein and nucleic acid co-isolates from conditioned 3D cell culture media. Compared to SEC, significantly higher EV yields with similar purity and preserved functionality were also obtained with MFC in 2D cell cultures. Additionally, MFC yielded EVs from serum with comparable purity to SEC and similar apolipoprotein B content. Overall, MFC presents an advancement in EV purification yielding EVs with high recovery, purity, and functionality, and offers an accessible improvement to researchers currently employing SEC.

Limited Nerve Regeneration across Acellular Nerve Allografts (ANAs) Coincides with Changes in Blood Vessel Morphology and the Development of a Pro-Inflammatory Microenvironment.

The use of acellular nerve allografts (ANAs) to reconstruct long nerve gaps (>3 cm) is associated with limited axon regeneration. To understand why ANA length might limit regeneration, we focused on identifying differences in the regenerative and vascular microenvironment that develop within ANAs based on their length. A rat sciatic nerve gap model was repaired with either short (2 cm) or long (4 cm) ANAs, and histomorphometry was used to measure myelinated axon regeneration and blood vessel morphology at various timepoints (2-, 4- and 8-weeks). Both groups demonstrated robust axonal regeneration within the proximal graft region, which continued across the mid-distal graft of short ANAs as time progressed. By 8 weeks, long ANAs had limited regeneration across the ANA and into the distal nerve (98 vs. 7583 axons in short ANAs). Interestingly, blood vessels within the mid-distal graft of long ANAs underwent morphological changes characteristic of an inflammatory pathology by 8 weeks post surgery. Gene expression analysis revealed an increased expression of pro-inflammatory cytokines within the mid-distal graft region of long vs. short ANAs, which coincided with pathological changes in blood vessels. Our data show evidence of limited axonal regeneration and the development of a pro-inflammatory environment within long ANAs.

Reduced capsaicin-induced mechanical allodynia and neuronal responses in the dorsal root ganglion in the presence of protein tyrosine phosphatase non-receptor type 6 overexpression.

Transient Receptor Potential Vanilloid 1 (TRPV1) is a nonselective cation channel expressed by pain-sensing neurons and has been an attractive target for the development of drugs to treat pain. Recently, Src homology region two domain-containing phosphatase-1 (SHP-1, encoded by Ptpn6) was shown to dephosphorylate TRPV1 in dorsal root ganglia (DRG) neurons, which was linked with alleviating different pain phenotypes. These previous studies were performed in male rodents only and did not directly investigate the role of SHP-1 in TRPV-1 mediated sensitization. Therefore, our goal was to determine the impact of Ptpn6 overexpression on TRPV1-mediated neuronal responses and capsaicin-induced pain behavior in mice of both sexes. Twelve-week-old male and female mice overexpressing Ptpn6 (Shp1-Tg) and their wild type (WT) littermates were used. Ptpn6 overexpression was confirmed in the DRG of Shp1-Tg mice by RNA in situ hybridization and RT-qPCR. Trpv1 and Ptpn6 were found to be co-expressed in DRG sensory neurons in both genotypes. Functionally, this overexpression resulted in lower magnitude intracellular calcium responses to 200 nM capsaicin stimulation in DRG cultures from Shp1-Tg mice compared to WTs. In vivo, we tested the effects of Ptpn6 overexpression on capsaicin-induced pain through a model of capsaicin footpad injection. While capsaicin injection evoked nocifensive behavior (paw licking) and paw swelling in both genotypes and sexes, only WT mice developed mechanical allodynia after capsaicin injection. We observed similar level of TRPV1 protein expression in the DRG of both genotypes, however, a higher amount of tyrosine phosphorylated TRPV1 was detected in WT DRG. These experiments suggest that, while SHP-1 does not mediate the acute swelling and nocifensive behavior induced by capsaicin, it does mediate a protective effect against capsaicin-induced mechanical allodynia in both sexes. The protective effect of SHP-1 might be mediated by TRPV1 dephosphorylation in capsaicin-sensitive sensory neurons of the DRG.

Periprosthetic Distal Femoral Fractures Around a Total Knee Arthroplasty: a Meta-analysis Comparing Locking compression Plating and Retrograde Intramedullary Nailing.

Purpose: The number of total knee replacements (TKRs) performed per year has been increasing annually and it is estimated that by 2030 demand would reach 3.48 million procedures per year in the United States Of America. The prevalence of periprosthetic fractures (PPFs) around TKRs has followed this trend with incidences ranging from 0.3% to 3.5%. Distal femoral PPFs are associated with significant morbidity and mortality. When there is sufficient bone stock in the distal femur and a fracture pattern conducive to fixation, locking compression plating (LCP) and retrograde intramedullary nailing (RIMN) are commonly used fixation strategies. Conversely, in situations with loosening and deficient bone stock, a salvage procedure such as a distal femoral replacement is recognized as an alternative. This meta-analysis investigates the rates of non-union, re-operation, infection, and mortality for LCPs and RIMNs when performed for distal femoral PPFs fractures around TKRs. Method: A search was conducted to identify articles relevant to the management of distal femoral PPFs around TKRs in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Articles meeting the inclusion criteria were then assessed for methodological quality using the methodological items for non-randomised studies (MINORS) criteria. Articles were reviewed, and data were compiled into tables for analysis. Results: 10 articles met the inclusion criteria, reporting on 528 PPFs. The overall incidence of complications was: non-union 9.4%, re-operation 12.9%, infection 2.4%, and mortality 5.5%. This meta-analysis found no significant differences between RIMN and LCP in rates of non-union (9.2% vs 9.6%) re-operation (15.1% vs 11.3%), infection (2.1% vs 2.6%), and mortality (6.0% vs 5.2%), respectively. Conclusion: This meta-analysis demonstrated no significant difference in rates of non-union, re-operation, infection, and mortality between RIMN and LCP and both remain valid surgical treatment options.

Distal femoral replacement for the treatment of periprosthetic distal femoral fractures around a total knee arthroplasty: a meta-analysis.

Background: Periprosthetic fracture is a rare complication of arthroplasty but can have devastating consequences for the patient and presents a complex surgical challenge. Locking compression plate and retrograde intramedullary nail are both widely accepted surgical fixation techniques for distal femoral periprosthetic fractures around a total knee arthroplasty. Although there is still a need for further high-quality research into both techniques, there is even less literature concerning the use of distal femoral replacement to treat distal femoral periprosthetic fractures. Interest has been piqued in distal femoral replacements for the treatment of distal femoral periprosthetic fractures due to the theoretical advantages of immediate post-operative weight-bearing and lack of dependence on fracture union, but there are still understandably reservations about performing such an extensive and invasive procedure when an accepted alternative is available. This meta-analysis aims to evaluate the current literature to compare the complication rates and return to pre-operative ambulatory status of distal femoral replacement and locking compression plate. Method: A literature search was performed to identify articles related to the management of distal femoral periprosthetic fractures around a total knee arthroplasty in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Methodological quality was assessed using the methodological index for non-randomized studies (MINORS) criteria. Articles were reviewed, and data extracted for analysis. Results: Five articles met the inclusion criteria, reporting on 345 periprosthetic fractures. The overall rates of complications for distal femoral replacement and locking compression plate were: re-operation (6.1% vs 12.1%), infection (3.0% vs 5.3%), mortality (19.7% vs 19.3%), and return to pre-operative ambulatory status (60.9% vs 71.8%) (respectively). Conclusion: This meta-analysis shows no statistically significant difference in the rates of re-operation, infection, mortality or return to pre-operative ambulatory status when comparing distal femoral replacement to locking compression plate.

Comprehensive analysis of MYB/MYBL1-altered pediatric-type diffuse low-grade glioma.

BACKGROUND: Pediatric-type diffuse low-grade gliomas (pLGG) harboring recurrent genetic alterations involving MYB or MYBL1 are closely related tumors. Detailed treatment and outcome data of large cohorts are still limited. This study aimed to comprehensively evaluate pLGG with these alterations to define optimal therapeutic strategies. METHODS: We retrospectively reviewed details of pLGG with MYB or MYBL1 alterations from patients treated or referred for pathologic review at St. Jude Children's Research Hospital. Tumor specimens were centrally reviewed, and clinical data were collated. RESULTS: Thirty-three patients (18 male; median age, 5 years) were identified. Two tumors had MYBL1 alterations; 31 had MYB alterations, MYB::QKI fusion being the most common (n = 10, 30%). Most tumors were in the cerebral hemispheres (n = 22, 67%). Two patients (6%) had metastasis at diagnosis. The median follow-up was 6.1 years. The 5-year event-free survival (EFS) rate was 81.3% ±â€…8.3%; the 5-year overall survival (OS) rate was 96.4% ±â€…4.1%. Patients receiving a near-total or gross-total resection had a 5-year EFS of 100%; those receiving a biopsy or subtotal resection had a 5-year EFS rate of 56.6% ±â€…15.2% (P < .01). No difference in EFS was observed based on location, histology, or molecular alterations. However, the tumors that progressed or metastasized may have distinct methylation profiles with evidence of activation of the MAPK and PI3K/AKT/mTOR pathways. CONCLUSIONS: pLGG with MYB/MYBL1 alterations have good outcomes. Our findings suggest that surgical resectability is a crucial determinant of EFS. Further characterization is required to identify optimal treatment strategies for progressive tumors.

Multiple surgical resections for progressive IDH wildtype glioblastoma-is it beneficial?

PURPOSE: The role of repeat resection for recurrent glioblastoma (rGB) remains equivocal. This study aims to assess the overall survival and complications rates of single or repeat resection for rGB. METHODS: A single-centre retrospective review of all patients with IDH-wildtype glioblastoma managed surgically, between January 2014 and January 2022, was carried out. Patient survival and factors influencing prognosis were analysed, using Kaplan-Meier and Cox regression methods. RESULTS: Four hundred thirty-two patients were included, of whom 329 underwent single resection, 83 had two resections and 20 patients underwent three resections. Median OS (mOS) in the cohort who underwent a single operation was 13.7 months (95% CI: 12.7-14.7 months). The mOS was observed to be extended in patients who underwent second or third-time resection, at 22.9 months and 44.7 months respectively (p < 0.001). On second operation achieving > 95% resection or residual tumour volume of < 2.25 cc was significantly associated with prolonged survival. There was no significant difference in overall complication rates between primary versus second (p = 0.973) or third-time resections (p = 0.312). The use of diffusion tensor imaging (DTI) guided resection was associated with reduced post-operative neurological deficit (RR 0.37, p = 0.002), as was use of intraoperative ultrasound (iUSS) (RR 0.45, p = 0.04). CONCLUSIONS: This study demonstrates potential prolongation of survival for rGB patients undergoing repeat resection, without significant increase in complication rates with repeat resections. Achieving a more complete repeat resection improved survival. Moreover, the use of intraoperative imaging adjuncts can maximise tumour resection, whilst minimising the risk of neurological deficit.

Crystal structure and analytical profile of 1,2-diphenyl-2-pyrrolidin-1-ylethanone hydrochloride or `α-D2PV': a synthetic cathinone seized by law enforcement, along with its diluent sugar, myo-inositol.

A confiscated package of street drugs was characterized by the usual mass spectral (MS) and FT-IR analyses. The confiscated powder material was highly crystalline and was found to consist of two very different species, accidentally of sizes convenient for X-ray diffraction. Thus, one each was selected and redundant complete sets of data were collected at 100 K using Cu Kα radiation. The selected crystals contained: (a) 1,2-diphenyl-2-(pyrrolidin-1-yl)ethanone hydrochloride hemihydrate or 1-(2-oxo-1,2-diphenylethyl)pyrrolidin-1-ium chloride hemihydrate, C18H20NO+·Cl-·0.5H2O, (I), a synthetic cathinone called `α-D2PV', and (b) the sugar myo-inositol, C6H12O6, (II), probably the only instance in which the drug and its diluent have been fully characterized from a single confiscated sample. Moreover, the structural details of both are rather attractive showing: (i) interesting hydrogen bonding observed in pairwise interactions by the drug molecules, mediated by the chloride counter-anions and the waters of crystallization, and (ii) π-π interactions in the case of the phenyl rings of the drug which are of two different types, namely, π-π stacking and edge-to-π. Finally, the inositol crystallizes with Z' = 2 and the resulting diastereoisomers were examined by overlay techniques.