An adaptable, reusable, and light implant for chronic Neuropixels probes.

Electrophysiology has proven invaluable to record neural activity, and the development of Neuropixels probes dramatically increased the number of recorded neurons. These probes are often implanted acutely, but acute recordings cannot be performed in freely moving animals and the recorded neurons cannot be tracked across days. To study key behaviors such as navigation, learning, and memory formation, the probes must be implanted chronically. An ideal chronic implant should (1) allow stable recordings of neurons for weeks; (2) be light enough for use in mice; (3) allow reuse of the probes after explantation. Here, we present the "Apollo Implant", an open-source and editable device that meets these criteria and accommodates up to two Neuropixels 1.0 or 2.0 probes. The implant comprises a "payload" module that is attached to the probe and is recoverable, and a "docking" module that is cemented to the skull. The design is adjustable, making it easy to change the distance between probes, the angle of insertion, and the depth of insertion. We tested the implant across seven labs in head-fixed mice, freely moving mice, and freely moving rats. The number of neurons recorded across days was stable, even after repeated implantations of the same probe. The Apollo implant provides an inexpensive, lightweight, and flexible solution for reusable chronic Neuropixels recordings.

What are the medicolegal implications of virtual clinics?

Recently there has been increased interest in the use and development of virtual clinics, particularly in the wake of the COVID-19 pandemic. The need to provide clinical care, while minimising patient interaction, has led to wider adoption of both telephone and online consultations, with the potential complications and pitfalls that accompany such a change in practice. A literature search was performed using the Pubmed, MEDLINE and Embase databases, from database inception up to 25 January 2021. A total of 21 papers were identified as discussing virtual clinical assessment and the medicolegal implications. The main areas of concern included consent, misdiagnosis, lack of physical examination, privacy and patient satisfaction. This article assesses these areas and suggests techniques to address them.

Accuracy of hospital-based surveillance systems for surgical site infection after adult spine surgery: a Bayesian latent class analysis.

BACKGROUND: Surgical site infections (SSIs) of the spine are morbid and costly complications. An accurate surveillance system is required to properly describe the disease burden and the impact of interventions that mitigate SSI risk. Unfortunately, uniform approaches to conducting SSI surveillance are lacking because of varying SSI case definitions, the lack of a perfect reference case definition and heterogeneous data sources. AIM: To assess the accuracy of four independent data sources that capture SSIs after spine surgery, with estimation of a measurement-error-adjusted SSI incidence. METHODS: A Bayesian latent class model assessed the sensitivity/specificity of each data source to identify SSI and to estimate a measurement-error-adjusted incidence. The four data sources used were: the discharge abstract database (DAD), the National Surgical Quality Improvement Program (NSQIP) database, the Infection Prevention and Control Canada (IPAC) database, and the Spine Adverse Events Severity database. FINDINGS: A total of 904 patients underwent spine surgery in 2017. The most sensitive data source was DAD (0.799; 95% credible interval (CrI): 0.597-0.943); the least sensitive was NSQIP (0.497; 95% CrI: 0.308-0.694). The most specific data source was IPAC (0.997; 95% CrI: 0.993-1.000) and the least specific was DAD (0.969; 95% CrI: 0.956-0.981). The measurement-error-adjusted SSI incidence was 0.030 (95% CrI: 0.019-0.045). The crude incidence using the DAD overestimated the incidence, and the three other data sources underestimated it. CONCLUSION: SSI surveillance in the spine surgery population is feasible using several data sources, provided that measurement error is considered.

Epitopes and motifs of the HLA-B*14 allele family products and related HLA-B14 cross-reactive specificities.

The split specificities of HLA-B14 (B64, B65) are assigned to the B*14:01 (B64) and B*14:02 (B65) products only. Of the further 50 B*14 expressed products, only B*14:03 and B*14:06 are officially designated as HLA-B14. The B*14:08 product differs from B64 by a single amino acid substitution of W97R, while the B*14:53 specificity (which is a "short" B14 and neither B64 nor B65) differs from B64 by three residues (W97S, Y113H and F116Y). Comprehensive testing of B*14:08:01 cells (using 49 alloantisera with B64 or B64, B65 specificities, and five monoclonal antibodies with B65 or B64, B65 activity) showed that the B*14:08 specificity is, like the B*14:53 product, neither B64 nor B65 and appears as a "short" B14 specificity. To help understand the serological reactivity of the B*14:08 and B*14:53 products, and B64 and B65, we identified seven published epitopes (11AV, 97W, 61ICT, 116F, 131S+163T, 170RH and 420) and, by inspection, 29 motifs, that encompass one or more of B64, B65 and various HLA-B14 cross-reactive group specificities. We then considered the possession of these epitopes and motifs by the products of B*14:01 to B*14:06, B*14:08 and B*14:53. Seventeen of the 29 motifs fully complied with the one-/two-patch functional epitope concept for amino acid proximity, as determined by Cn3D software, the remainder partially complied. The nature and patterns of epitopes and motifs possessed by both B*14:08 and B*14:53 specificities supported their designation as HLA-B14 but non-B64/B65. Also that epitope 97W, with 11S or 11A, is critical for serological B64 and B65 reactivity. And conversely, that epitope 116F, and several identified motifs, are probably unimportant for HLA-B14 antibody reactivity. The previous submission that the B*14:03 specificity is HLA-B65 was compatible with its epitope/motif pattern. B*14:04 cells would also be expected to react as B65, based on its epitope/motif pattern, and not as B64 as previously implied. Also, from their epitope/motif patterns, and external serological information, it is probable that the B*14:05 and B*14:06 specificities will both appear as "short" HLA-B14, non-B64/B65. Several epitopes and motifs encompassed a range of HLA-B specificities included in the serological HLA-B14 cross-reactive group, thus supporting these original serological findings.

Three new HLA alleles-B*49:43, C*03:321 and DQB1*02:72.

Immunogenetic information is provided on 3 novel HLA-B, -C and -DQB1 alleles.

Urine Exosomes: An Emerging Trove of Biomarkers.

Exosomes are released by most cells and can be isolated from all biofluids including urine. Exosomes are small vesicles formed as part of the endosomal pathway that contain cellular material surrounded by a lipid bilayer that can be traced to the plasma membrane. Exosomes are potentially a more targeted source of material for biomarker discovery than unfractionated urine, and provide diagnostic and pathophysiological information without an invasive tissue biopsy. Cytoplasmic contents including protein, mRNA, miRNA, and lipids have all been studied within the exosomal fraction. Many prospective urinary exosomal biomarkers have been successfully identified for a variety of kidney or genitourinary tract conditions; detection of systemic conditions may also be possible. Isolation and analysis of exosomes can be achieved by several approaches, although many require specialized equipment or involve lengthy protocols. The need for timely analysis in the clinical setting has driven considerable innovation with several promising options recently emerging. Consensus on exosome isolation, characterization, and normalization procedures would resolve critical clinical translational bottlenecks for existing candidate exosomal biomarkers and provide a template for additional discovery studies.

The differential effects of norepinephrine and dopamine on cerebrospinal fluid pressure and spinal cord perfusion pressure after acute human spinal cord injury.

STUDY DESIGN: Prospective vasopressor cross-over interventional studyObjectives:To examine how two vasopressors used in acute traumatic spinal cord injury (SCI) affect intrathecal cerebrospinal fluid pressure and the corresponding spinal cord perfusion pressure (SCPP). SETTING: Vancouver, British Columbia, Canada. METHODS: Acute SCI patients over the age of 17 with cervical or thoracic ASIA Impairment Scale (AIS). A, B or C injuries were enrolled in this study. Two vasopressors, norepinephrine and dopamine, were evaluated in a 'crossover procedure' to directly compare their effect on the intrathecal pressure (ITP). The vasopressor cross-over procedures were performed in the intensive care unit where ITP, mean arterial pressure (MAP) and heart rate were being continuously measured. The SCPP was calculated as the difference between MAP and ITP. RESULTS: A total of 11 patients were enrolled and included in our analysis. There were 6 patients with AIS A, 3 with AIS B and 2 with AIS C injuries at baseline. We performed 24 cross-over interventions in these 11 patients. There was no difference in MAP with the use of norepinephrine versus dopamine (84±1 mm Hg for both; P=0.33). Conversely, ITP was significantly lower with the use of norepinephrine than with dopamine (17±1 mm Hg vs 20±1 mm Hg, respectively, P<0.001). This decrease in ITP with norepinephrine resulted in an increased SCPP during the norepinephrine infusion when compared with dopamine (67±1 mm Hg vs 65±1 mm Hg respectively, P=0.0049). CONCLUSION: Norepinephrine was able to maintain MAP with a lower ITP and a correspondingly higher SCPP as compared with dopamine in this study. These results suggest that norepinephrine may be preferable to dopamine if vasopressor support is required post SCI to maintain elevated MAPs in accordance with published guidelines.

A further HLA-DRB1*15 family allele - DRB1*15:112.

HLA-DRB1*15:112 differs from DRB1*15:01:01:01 by one base (282G > T) in exon 2 resulting in K65N.

Two new HLA class I alleles - A*11:241 and C*08:132.

HLA-A*11:241 differs from A*11:01:01:01 (215G > A, exon 2, R48Q); HLA-C*08:132 from C*08:02:01:01 (587 T > A exon 3, L172Q).

Five new HLA alleles with synonymous mutations: A*01:01:65, A*01:01:66, B*44:03:35, DRB1*15:01:30 and DQB1*02:01:24.

Immunogenetic information is provided on five novel alleles with synonymous mutations.

A novel HLA-B*14 allele - B*14:53 - genetics and serology.

HLA-B*14:53 was found in a UK European normal blood donor prior to registration on the Welsh Bone Marrow Donor Registry. It differs from B*14:13 by one base (103G>T) in exon 2 resulting in a substitution of alanine (A) in B*14:13 to serine (S) in B*14:53. Unique among current HLA-B*14 alleles, B*14:53 and B*14:13 share a motif of 59 bases between positions 361 and 419 in exon 3. This motif is present in numerous HLA-B alleles the commonest overall being B*08:01, suggesting that both B*14:53 and B*14:13 arose from intralocus gene conversion events with B*08:01. Thus, B*14:53 probably arose from B*14:01:01 (which has TCC at codon 11 (S), while B*14:13 arose from B*14:02:01:01 which has GCC at codon 11 (A). Additionally, the two likely B*14:53-bearing and B*14:13-bearing haplotypes are typical of B*14:01:01-bearing and B*14:02:01:01-bearing haplotypes, respectively. Serological testing, using 49 antisera with HLA-B64, or B64, B65 reactivity, showed that the B*14:53 specificity did not react as a B64 (B*14:01) specificity and may appear as a short/weak HLA-B14. This implies that residues additional to S at position 11 are involved in HLA-B64 serological identity; for example, the motif 11S 97W 116F is possessed by B*14:01 and many other B*14 products (and B*39:79 plus some HLA-C products) but not B65 (B*14:02) or the B*14:53 specificity. B*14:53 was found in a random HLA sequence-based typed population of 32 530 normal subjects indicating a low precision allele frequency of 0.000015 in subjects resident in Wales.

A further HLA-A*23 family allele--HLA-A*23:68.

HLA-A*23:68 differs from A*23:01:01 by one base (518C > A) in exon 3 resulting in an amino acid substitution of A149E.

Immunogenetics of three novel HLA-Class II alleles: DRB1*03:112, DQB1*03:02:16 and DQB1*03:139.

Three novel HLA-Class II alleles, DRB1*03:112, DQB1*03:02:16 and DQB1*03:139, are described with predicted bearing haplotypes of A*02:01, B*40:01, C*03:04, DRB1*03:112, DQB1*02:01; A*23:01, B*15:01, C*03:03, DRB1*04:01, DQB1*03:02:16 and A*01:01, B*44:02, C*05:01/03, DRB1*04:01, DQB1*03:139. Serological tests showed that the DRB1*03:112 and DQB1*03:139 specificities failed to react as expected with some well-documented monoclonal antibodies. Subsequent examination of published HLA-Class II epitopes and inspection of amino acid motifs suggested that epitopes exist that include the positions of their single substitutions (F31C between DRB1*03:01:01:01 and DRB1*03:112, and R48P between DQB1*03:01:01:01 and DQB1*03:139 specificities). This suggests that the reactivity of the monoclonal antibodies used was dependent on these epitopes and that their loss from these rare allele products resulted in their aberrant serology. The new alleles were found after the sequence-based typing of 32 530 random UK European routine blood donors suggesting that each has a maximum carriage frequency of 0.0031% in the blood donor population resident in Wales.

Utility of the Tono-Pen in Measuring Intraocular Pressure in Trinidad: A Cross-sectional Study.

AIM: To determine the sensitivity and specificity of the Reichert™ Tono-Pen AVIA® when used by novice medical students in an ethnically diverse population in Trinidad. SUBJECTS AND METHOD: Participants were residents of Trinidad between the ages of 20 and 90 years attending the Ophthalmology Clinic at the Eric Williams Medical Sciences Complex (EWMSC). Intraocular pressure (IOP) was measured using the Goldmann applanation tonometer (the gold standard) for ophthalmology clinic patients as part of their routine care. Intraocular pressure measurements were then taken using the Tono-Pen. RESULTS: One hundred persons participated, consisting of Indo-Trinidadians (55%), Afro-Trinidadians (36%), Mixed (8%) and 1% of Caucasian descent. Fourteen per cent reported a diagnosis of glaucoma, with 70.6% of these being of African descent. One hundred and ninety-eight readings of IOP were taken. At a cut-off point of 21 mmHg, there were nine true positives, four false positives, seven false negatives and 178 true negatives. The sensitivity and specificity were found to be 56.3% (95% CI 33.2, 76.9) and 97.8% (95% CI 94.5, 99.1), respectively. The positive predictive value was calculated as 69.2% (95% CI 42.4, 87.3) while the negative predictive value was 96.2% (95% CI 92.4, 98.2). The prevalence of elevated IOP in this population was 8.1% (95% CI 4.8, 13.0). The likelihood ratio of a positive result was calculated to be 25.6 (95% CI 8.6, 73.9). CONCLUSION: The high specificity and negative predictive value suggests that the Tono-Pen can be used with minimal training, and can prove beneficial at the primary care level in the exclusion of increased IOP in an ethnically diverse high-risk Caribbean population.

Three new HLA-DQB1 alleles ­ DQB1*03:113, DQB1*06:02:15 and DQB1*06:129.

Three novel HLA-DQB1 alleles were found after sequence-based typing of 3558 random UK European routine blood donors.

A new HLA-A*26 family allele--HLA-A*26:103.

HLA-A*26:103 differs from A*26:01:01 by one base (559C>G) in exon 3 resulting in an amino acid substitution of R163G.

Cervical spine injuries and flexibilities following axial impact with lateral eccentricity.

PURPOSE: Determine the effects of dynamic injurious axial compression applied at various lateral eccentricities (lateral distance to the centre of the spine) on mechanical flexibilities and structural injury patterns of the cervical spine. METHODS: 13 three-vertebra human cadaver cervical spine specimens (6 C3-5, 3 C4-6, 2 C5-7, 2 C6-T1) were subjected to pure moment flexibility tests (±1.5 Nm) before and after impact trauma was applied in two groups: low and high lateral eccentricity (1 and 150 % of the lateral diameter of the vertebral body, respectively). Relative range of motion (ROM) and relative neutral zone (NZ) were calculated as the ratio of post and pre-trauma values. Injuries were diagnosed by a spine surgeon and scored. Classification functions were developed using discriminant analysis. RESULTS: Low and high eccentric loading resulted in primarily bony fractures and soft tissue injuries, respectively. Axial impacts with high lateral eccentricities resulted in greater spinal motion in lateral bending [median relative ROM 3.5 (interquartile range, IQR 2.3) vs. 1.4 (IQR 0.5) and median relative NZ 4.7 (IQR 3.7) vs. 2.3 (IQR 1.1)] and in axial rotation [median relative ROM 5.3 (IQR 13.7) vs. 1.3 (IQR 0.5), p < 0.05 for all comparisons] than those that resulted from low eccentricity impacts. The developed classification functions had 92 % classification accuracy. CONCLUSIONS: Dynamic axial compression loading of the cervical spine with high lateral eccentricities produced primarily soft tissue injuries resulting in more post-injury spinal flexibility in lateral bending and axial rotation than that associated with the bony fractures resulting from low eccentricity impacts.

Reliability of the spine adverse events severity system (SAVES) for individuals with traumatic spinal cord injury.

STUDY DESIGN: Test-retest analysis. OBJECTIVES: To determine the intra- and inter-rater reliability of the Spine Adverse Events Severity System for Spinal Cord Injury (SAVES-SCI) in patients with traumatic SCI. SETTING: Quaternary care spine program in Vancouver, Canada. METHODS: Ten hypothetical patient cases were developed. The cases were completed by 10 raters (seven physicians, one nurse, one physiotherapist and one researcher) who were asked to identify and grade the severity of adverse events using SAVES-SCI twice with 1-week interval. Intra- and inter-rater reliability were calculated using kappa statistics and intraclass correlation coefficients (ICC). RESULTS: Intra-rater reliability for both identifying and grading AEs were high with all AEs (kappa greater than 0.6) except for bone implant, diathermy burn, massive blood loss, myocardial infarction, neurological deterioration, pressure ulcer, return to operating room and tracheostomy requirement. The inter-rater reliability measured with ICC were all above 0.6 for identifying and grading intraoperative, pre and postoperative AEs and consequences of SCI. CONCLUSIONS: The SAVES-SCI demonstrated acceptable intra-and inter-rater reliability for a majority of the AEs. Further clarification and definition of some of the AEs as well as provision of sample training cases for clinicians would assist in reducing measurement errors. The SAVES-SCI is a useful tool to assess and capture AEs in patients with acute traumatic SCI.

Fifty years of human space travel: implications for bone and calcium research.

Calcium and bone metabolism remain key concerns for space travelers, and ground-based models of space flight have provided a vast literature to complement the smaller set of reports from flight studies. Increased bone resorption and largely unchanged bone formation result in the loss of calcium and bone mineral during space flight, which alters the endocrine regulation of calcium metabolism. Physical, pharmacologic, and nutritional means have been used to counteract these changes. In 2012, heavy resistance exercise plus good nutritional and vitamin D status were demonstrated to reduce loss of bone mineral density on long-duration International Space Station missions. Uncertainty continues to exist, however, as to whether the bone is as strong after flight as it was before flight and whether nutritional and exercise prescriptions can be optimized during space flight. Findings from these studies not only will help future space explorers but also will broaden our understanding of the regulation of bone and calcium homeostasis on Earth.

Evaluation of a pilot Pressure Ulcer Prevention Initiative (PUPI) for patients with traumatic spinal cord injury.

OBJECTIVE: The purpose of this study was to determine whether implementation of a Pressure Ulcer Prevention Initiative (PUPI) changed the assessment and treatment of patients with a traumatic spinal cord injury (SCI) in an acute care setting, and improved patient outcomes. METHOD: The success of implementation was evaluated by examining the percentage of patients with completed occupational therapist (OT) skin care assessments and prescriptions for therapeutic support surfaces (TSS; i.e., mattresses) before implementation (historical, cohort 1) and after implementation (experimental, cohort 2). Patient outcomes were evaluated by examining changes in PU incidence, severity, timing and recurrence, as well as PU prevalence and satisfaction with life in the community. RESULTS: Final analysis included 70 patients in cohort 1 and 73 in cohort 2. OT skin care assessment documentation (31% to 60%; p<0.001) and TSS prescriptions (31% to 60%; p=0.02) significantly increased following the implementation. The PU incidence based on patient charts (both nursing and OT assessments) did not increase significantly (26% to 36%; p=0.2). However, documented PU incidence according to OT assessments showed a substantial increase (14% to 33%; p=0.002). No effect of the PUPI was seen on immediate or long-term patient outcomes during the study period. CONCLUSION: PUPI was successful in changing clinical practice in PU prevention but no statistically significant improvements in PU-related patient outcomes were demonstrated. Results from this study identified facilitators and barriers to implementation and highlighted the complexity and difficulty of instituting effective preventative or therapeutic interventions for this population in an acute care setting. This information will assist with refinements of the PUPI and inform similar future initiatives.