Achieving Specified Laxity in a Noncruciate Total Knee: A Laboratory Design Study.

BACKGROUND: Noncruciate total knee arthroplasty designs, including ultracongruent, medially congruent, and medial pivot, are gaining increasing attention in total knee arthroplasty surgery. However, there is no consensus for the bearing surface design, whether there should be different medial, lateral, anterior, and posterior laxities, or whether the medial side should be a medial pivot. This study proposes the criterion of reproducing the laxity of the anatomic knee, defined as the displacements and rotations of the femur on the tibia in the loaded knee when shear and torque are applied. The purpose of this study was to determine the ideal tibial radii to achieve that goal. METHODS: The femoral component was based on the average knee from 100 mild arthritic knee scans. There were 8 tibial components that were designed with different sagittal radii: antero-medial, antero-lateral, postero-medial, and postero-lateral. Radii were defined as the percent height reduction from full conformity with the femoral profile. Components were 3-dimensional-printed. A test rig was constructed where the tibial component was fixed and shear and torque were applied to the femoral component. Displacements and rotations of the femoral component were measured at 0 and 45° of flexion, the latter representing any flexion angle due to the constant femoral sagittal radius. RESULTS: Displacements ranged from 0 to 11 mm, and rotations ranged from 1 to 11°. Anterior femoral displacements were higher than posterior due to the shallow distal-anterior femoral profile. The final femoral and tibial components with the most closely matched anatomic laxity values were designed and tested. CONCLUSIONS: A steeper distal-anterior femoral radius was an advantage. High medial-anterior tibial conformity was important. However, on the lateral side, the posterior sagittal tibial radius had to be shallower than ideal to allow femoral rollback in high flexion. This meant that the posterior laxity displacements on the lateral side were higher than anatomic, and there was no guidance for lateral femoral rollback.

Robotic-assisted burring in total hip replacement: A new surgical technique to optimise acetabular preparation.

BACKGROUND: In Total Hip replacement (THR) surgery, a critical step is to cut an accurate hemisphere into the acetabulum so that the component can be fitted accurately and obtain early stability. This study aims to determine whether burring rather than reaming the acetabulum can achieve greater accuracy in the creation of this hemisphere. METHODS: A preliminary robotic system was developed to demonstrate the feasibility of burring the acetabulum using the Universal Robot (UR10). The study will describe mechanical design, robot trajectory optimisation, control algorithm development, and results from phantom experiments compared with both robotic reaming and conventional reaming. The system was also tested in a cadaver experiment. RESULTS: The proposed robotic burring system can produce a surface in 2 min with an average error of 0.1 and 0.18 mm, when cutting polyurethane bone block #15 and #30, respectively. The performance was better than robotic reaming and conventional hand reaming. CONCLUSION: The proposed robotic burring system outperformed robotic and conventional reaming methods to produce an accurate acetabular cavity. The findings show the potential usage of a robotic-assisted burring in THR for acetabular preparation.

Frequency of Clinically Significant Findings in the Surgical Pathology Specimen Following Laparoscopic Sleeve Gastrectomy and Concordance with Preoperative Endoscopy: Insights from a Large Single-Center Experience.

INTRODUCTION: Endoscopy prior to bariatric surgery is not always performed, and in sleeve gastrectomy (SG), the surgical specimen is not always sent for pathological examination. There is limited data on the frequency of clinically significant findings in SG specimens or correlation with preoperative endoscopy. METHODS: We reviewed 426 consecutive SG patients to determine the concordance of preoperative endoscopy findings in patients with clinically significant postoperative pathology. RESULTS: Preoperative endoscopy was performed on 397 patients (93.2%). Three hundred seventy-three patients had preoperative endoscopy and surgical pathology results available. Then, 20/373 (5.4%) patients had potentially significant postoperative pathology, including intestinal metaplasia, autoimmune metaplastic atrophic gastritis (AMAG), gastrointestinal stromal tumors, and/or gastric cancer. The overall incidence of AMAG in the entire cohort was 2.3%. Preoperative gastric biopsies (to include gastric body) identified AMAG in nearly 1/2 of patients. Patients with clinically significant postoperative pathology results had a median [interquartile range] of 3 [3-5] tissue blocks examined as compared to 3 [1-3] for the remainder of the cohort (p < 0.001). CONCLUSION: This is one of the largest studies describing clinically significant postoperative pathology after SG. AMAG, in particular, is of particular importance as it is associated with a 3-fivefold increase in risk for gastric cancer. The incidence of significant postoperative pathology in this population is small but potentially clinically significant and requires validation in larger studies. We recommend wider sampling in preoperative endoscopy (body and antrum), especially in patients being planned for gastric bypass, consideration for routine pathological examination of SG surgical specimens, with careful gross examination and targeted sampling.

Design and evaluation of a 3D printed mechanical balancer for soft tissue balancing in total knee replacement.

PURPOSE: Soft tissue balancing is an important step in a total knee procedure, carried out manually, or using an indicator. The purpose of this study was to evaluate our design of 3D printed Balancer, and demonstrate how it could be used at surgery. PROCEDURES: When inserted between the femur and tibia, the Balancer displayed the forces acting across the lateral and medial compartments, indicated by pointers at the end of the handle. A loading rig was used to measure the pointer deflections for different forces applied at different locations on the condyle surfaces. Repeatability and reproducibilty were evaluated. The Balancer was tested in six fresh knee specimens using a surgical simulation rig. MAIN FINDINGS: Pointer deflections of up to 12 millimeters occurred for less than 1 mm displacements at the condyle surfaces. Reproducibility tests showed a standard deviation of 14% at lower loads, reducing to only 4% at higher loads. Mean pointer deflections were within 8% for forces applied at ±10 mm AP, and +5/-3 mm in an ML direction, relative to the neutral contact point. In specimens, most lateral to medial force differences could be corrected by a 2° change in frontal plane angle of the tibial resection. Effects of ligament releases were also demonstrated. PRINCIPAL CONCLUSIONS: The 3D printed Balancer was easy to use, and provided the surgeon with lateral and medial force data over a full range of flexion, enabling possible corrective procedures to be specified.

Burnout and depression: Points of convergence and divergence.

BACKGROUND: Debate is ongoing as to whether burnout can be differentiated from depression. This study evaluated whether burnout and depression could be distinguished using a new burnout measure and other variables. METHODS: Scores on the Sydney Burnout Measure (SBM) were compared between participants with self-diagnosed burnout (BO-all group; n = 622) and clinically-diagnosed depression (DEP-all group; n = 90). The latter group was split into melancholic (DEP-mel; n = 56) and non-melancholic (DEP-nonmel; n = 34) depression subgroups for subsequent analyses. Differences in reporting of depressive symptoms and causal attributions were also evaluated. RESULTS: While total SBM scores showed poor differentiation, the BO-all group had lower social withdrawal and higher empathy loss subscale scores than the depression groups. Odds ratios were significant for several of the depressive symptoms and causal attribution items when comparing the BO-all group to the DEP-all and DEP-mel groups, while only a few items were significant when comparing the BO-all and DEP-nonmel groups. LIMITATIONS: Participants in the depression group were assigned by clinician-based depression diagnoses, rather than by a standardised diagnostic interview, and the group had a relatively small sample size. Participants in the burnout group were self-diagnosed and not assessed for comorbid psychiatric diagnoses. CONCLUSIONS: There were some nuanced symptoms differences between burnout and depression, but many of the SBM symptoms were not specific to burnout. Results also suggested that burnout overlaps more with non-melancholic than melancholic depression, and that differentiation of burnout and depression may rely more on weighting causal factors over symptoms.

Perception of Size and Mass Relationships of Moving and Stationary Object in Collision Events in 10-to-11-Month-Old Infants.

Around 5.5-6.5 months of age, infants first attend to object size and perceive its mass cues in simple collision events. Infants attend to the size of the moving object and expect a greater displacement following a collision with a large object and stationary object, and lesser displacement following a collision with a small object and stationary object. It has been proposed that infants of 6-to-7 months of age can differentiate between sizes of moving objects but do not perceive the size and mass relationships in simple collision events. The present two investigations aimed to investigate whether infants 10-to-11 months of age (N = 16) could perceive this relationship (experiment 1) and the reverse of this relationship (experiment 2) utilising the looking time paradigm. The reverse of this relationship entailed the circumstances in which the moving object size was kept constant, but the stationary object size varied (small or large). Results from these experiments revealed that infants did not differ in their looking times for size congruent and size incongruent distances in both conditions. Infants did not look longer at the incongruent test events that violated expectation. For that reason, we conclude infants of 10-to-11 months of age were unable to perceive size and mass associations in collision events in either direction (moving object or stationary object size).

Modelling self-diagnosed burnout as a categorical syndrome.

OBJECTIVE: There is currently little consensus as to how burnout is best defined and measured, and whether the syndrome should be afforded clinical status. The latter issue would be advanced by determining whether burnout is a singular dimensional construct varying only by severity (and with some level of severity perhaps indicating clinical status), or whether a categorical model is superior, presumably reflecting differing 'sub-clinical' versus 'clinical' or 'burning out' vs 'burnt out' sub-groups. This study sought to determine whether self-diagnosed burnout was best modelled dimensionally or categorically. METHODS: We recently developed a new measure of burnout which includes symptoms of exhaustion, cognitive impairment, social withdrawal, insularity, and other psychological symptoms. Mixture modelling was utilised to determine if scores from 622 participants on the measure were best modelled dimensionally or categorically. RESULTS: A categorical model was supported, with the suggestion of a sub-syndromal class and, after excluding such putative members of that class, two other classes. Analyses indicated that the latter bimodal pattern was not likely related to current working status or differences in depression symptomatology between participants, but reflected subsets of participants with and without a previous diagnosis of a mental health condition. CONCLUSION: Findings indicated that sub-categories of self-identified burnout experienced by the lay population may exist. A previous diagnosis of a mental illness from a mental health professional, and therefore potentially a psychological vulnerability factor, was the most likely determinant of the bimodal data, a finding which has theoretical implications relating to how best to model burnout.

Enhanced Vaccine Effectiveness during the Delta Phase of the COVID-19 Pandemic in the Medicare Population Supports a Multilayered Prevention Approach.

Throughout the pandemic, individuals 65 years and older have contributed most COVID-19 related deaths. To best formulate effective vaccination and other prevention policies to protect older adults, large scale observational studies of these higher risk individuals are needed. We conducted a Vaccine Effectiveness (VE) study during the B.1.617.2 Delta variant phase of the pandemic in July and August 2021 in a cohort of 17 million Medicare beneficiaries of which 5.7 million were fully vaccinated. We found that individuals fully vaccinated with the Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 vaccines in January 2021 had 2.5 times higher breakthrough infections and hospitalizations than those fully vaccinated in March 2021, consistent with waning of vaccine-induced immunity. Measuring VE weekly, we found that VE against hospitalization, and even more so against infection, increased from July 2021 through August 2021, suggesting that in addition to the protective role of vaccination, increased masking or social distancing might have contributed to the unexpected increase in VE. Ongoing monitoring of Medicare beneficiaries should be a priority as new variants continue to emerge, and the VE of the new bivalent vaccines remains to be established. This could be accomplished with a large Medicare claims database and the analytics platform used for this study.

Palliative Endoscopic Salvage of a Functionally Obstructed Gastrojejunostomy - Report of Technique.

Background: Gastric outlet obstruction secondary to foregut gastrointestinal malignancies can be managed with a variety of medical, endoscopic, and surgical options. Laparoscopic gastrojejunostomy is an option for those patients who are able to tolerate an operation as a long-term palliative option. This operation may be associated with some significant postoperative technical and nontechnical complications, including delayed gastric emptying. This paper describes an incision-less, endoscopic option that we propose can be used to salvage a functionally obstructed gastrojejunostomy. Case Description: A 57-year old male patient had a history of pancreatic adenocarcinoma causing gastric outlet obstruction and underwent a previously created surgical gastrojejunostomy at an outside hospital. His procedure was complicated by anastomotic leak and essentially persistent obstructive symptoms secondary to delayed gastric emptying. Though his anastomosis was demonstrably patent, these symptoms were thought to be secondary to a functional obstruction at the gastrojejunostomy. After repeated workups and many failed attempts to treat these symptoms, he ultimately underwent endoscopic placement of an uncovered colonic stent into the efferent limb of his gastrojejunostomy. This allowed for preferential drainage of gastric contents down the efferent limb, and improvement of his delayed gastric emptying. Conclusions: In a select group of patients with advanced foregut malignancy, and with high re-operative risks, salvage endoscopic stenting may be useful in the palliation of symptoms from a functionally obstructed gastrojejunostomy.

Recent changes to virus taxonomy ratified by the International Committee on Taxonomy of Viruses (2022).

This article reports the changes to virus taxonomy approved and ratified by the International Committee on Taxonomy of Viruses (ICTV) in March 2022. The entire ICTV was invited to vote on 174 taxonomic proposals approved by the ICTV Executive Committee at its annual meeting in July 2021. All proposals were ratified by an absolute majority of the ICTV members. Of note, the Study Groups have started to implement the new rule for uniform virus species naming that became effective in 2021 and mandates the binomial 'Genus_name species_epithet' format with or without Latinization. As a result of this ratification, the names of 6,481 virus species (more than 60 percent of all species names currently recognized by ICTV) now follow this format.

Nationally Informed Recommendations on Approaching the Detection, Assessment, and Management of Mild Cognitive Impairment.

Prior to the usual clinical symptoms of dementia, there can be subtle changes in cognitive function that differ from the normal age-related cognitive decline, which has been termed mild cognitive impairment (MCI). The increase in the numbers of individuals with possible MCI presenting to health care professionals, notably, General Practitioners (GPs), is going to rise dramatically in the coming years. With ever increasing demands on GPs, it is therefore timely to provide information that can be accessed by health care professionals to assist them in making appropriate diagnoses and to provide the most relevant, evidence-based treatment options. We have provided a comprehensive list of recommendations that aim to address key aspects of MCI in primary care. Specifically, these relate to detection and diagnosis; sharing the diagnosis, monitoring, and follow up; practical interventions to potentially delay progression; and personalizing care-planning, engagement, and patient motivation for the long term.

Exploiting Violet-Blue Light to Kill Campylobacter jejuni: Analysis of Global Responses, Modeling of Transcription Factor Activities, and Identification of Protein Targets.

Campylobacter jejuni is a microaerophilic foodborne zoonotic pathogen of worldwide concern as the leading cause of bacterial gastroenteritis. Many strains are increasingly antibiotic resistant and new methods of control are required to reduce food-chain contamination. One possibility is photodynamic inactivation (PDI) using violet-blue (VB) light, to which C. jejuni is highly susceptible. Here, we show that flavin and protoporphyrin IX are major endogenous photosensitizers and that exposure of cells to VB light increases intracellular reactive oxygen species (ROS) to high levels, as indicated by a dichlorodihydrofluorescein reporter. Unusually for an oxygen-respiring bacterium, C. jejuni employs several ROS-sensitive iron-sulfur cluster enzymes in central metabolic pathways; we show that VB light causes rapid inactivation of both pyruvate and 2-oxoglutarate oxidoreductases, thus interrupting the citric acid cycle. Cells exposed to VB light also lose heme from c-type cytochromes, restricting electron transport, likely due to irreversible oxidation of heme-ligating cysteine residues. Evaluation of global gene expression changes by RNAseq and probabilistic modeling showed a two-stage protein damage/oxidative stress response to VB light, driven by specific regulators, including HspR, PerR, Fur, and RacR. Deletion mutant analysis showed that superoxide dismutase and the cytochrome CccA were particularly important for VB light survival and that abolishing repression of chaperones and oxidative stress resistance genes by HcrA, HspR, or PerR increased tolerance to VB light. Our results explain the high innate sensitivity of C. jejuni to VB light and provide new insights that may be helpful in exploiting PDI for novel food-chain interventions to control this pathogen. IMPORTANCE Campylobacteriosis caused by C. jejuni is one of the most widespread zoonotic enteric diseases worldwide and represents an enormous human health and economic burden, compounded by the emergence of antibiotic-resistant strains. New interventions are urgently needed to reduce food-chain contamination. Although UV light is well known to be bactericidal, it is highly mutagenic and problematic for continuous exposure in food production facilities; in contrast, narrow spectrum violet-blue (VB) light is much safer. We confirmed that C. jejuni is highly susceptible to VB light and then identified some of the global regulatory networks involved in responding to photo-oxidative damage. The identification of damaged cellular components underpins efforts to develop commercial applications of VB light-based technologies.

Evaluation of maximum dose intravenous midazolam used in dental intravenous sedation: a West of Scotland regional audit.

Background Intravenous (IV) midazolam sedation is commonly used in the delivery of dentistry for phobic patients. There is currently no guidance on a maximum dose for use specifically in dentistry. Dentists practise with the British National Formulary recommended maximum dose of 7.5 mg; however, anecdotally, this is often exceeded. We aim to evaluate prescribing and propose recommendations for a maximum dose for dentists.Method Data was collected from ten dentists across four Scottish health boards regarding their last 20 IV sedation patients, giving a total of 200. Data obtained from standard Dental Sedation Teachers Group IV logbooks included: dose of midazolam administered; justification for doses over 7.5 mg; flumazenil or supplemental oxygen usage; significant medical/social factors; and the Ramsay Sedation Score.Results Mean midazolam dose was 6.1 mg with a range of 14 mg. The recommended maximum dose of 7.5 mg was exceeded in 28% of cases. The mean sedation score was 2.7 and there were no reported adverse events or use of flumazenil.Conclusion IV midazolam is an effective way to achieve conscious sedation in dentistry. Acknowledgement of current off-label prescribing is important; however, 7.5 mg as a recommended maximum dose is too conservative as it is regularly exceeded without adverse events. Further investigation and expert opinion is required to set a maximum dose specifically for dentistry.

ICTV Virus Taxonomy Profile: Rhabdoviridae 2022.

The family Rhabdoviridae comprises viruses with negative-sense (-) RNA genomes of 10-16 kb. Virions are typically enveloped with bullet-shaped or bacilliform morphology but can also be non-enveloped filaments. Rhabdoviruses infect plants or animals, including mammals, birds, reptiles, amphibians or fish, as well as arthropods, which serve as single hosts or act as biological vectors for transmission to animals or plants. Rhabdoviruses include important pathogens of humans, livestock, fish or agricultural crops. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Rhabdoviridae, which is available at ictv.global/report/rhabdoviridae.

Revised Taxonomy of Rhabdoviruses Infecting Fish and Marine Mammals.

The Rhabdoviridae is a large family of negative-sense (-) RNA viruses that includes important pathogens of ray-finned fish and marine mammals. As for all viruses, the taxonomic assignment of rhabdoviruses occurs through a process implemented by the International Committee on Taxonomy of Viruses (ICTV). A recent revision of taxonomy conducted in conjunction with the ICTV Rhabdoviridae Study Group has resulted in the establishment of three new subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae) within the Rhabdoviridae, as well as three new genera (Cetarhavirus, Siniperhavirus, and Scophrhavirus) and seven new species for viruses infecting fish or marine mammals. All rhabdovirus species have also now been named or renamed to comply with the binomial format adopted by the ICTV in 2021, comprising the genus name followed by a species epithet. Phylogenetic analyses of L protein (RNA-dependent RNA polymerase) sequences of (-) RNA viruses indicate that members of the genus Novirhabdovirus (subfamily Gammarhabdovirinae) do not cluster within the Rhabdoviridae, suggesting the need for a review of their current classification.

Elevations in Tumor Necrosis Factor Alpha and Interleukin 6 From Neuronal-Derived Extracellular Vesicles in Repeated Low-Level Blast Exposed Personnel.

Objective: The purpose of this pilot study was to determine if military service members with histories of hundreds to thousands of low-level blast exposures (i. e., experienced breachers) had different levels of serum and neuronal-derived extracellular vesicle (EV) concentrations of interleukin (IL)-6, IL-10, and tumor necrosis factor alpha (TNFα), compared to matched controls, and if these biomarkers related to neurobehavioral symptoms. Methods: Participants were experienced breachers (n = 20) and matched controls without blast exposures (n = 14). Neuronal-derived EVs were isolated from serum and identified with mouse anti-human CD171. Serum and neuronal-derived EVs were analyzed for IL-6, IL-10, and TNFα using an ultra-sensitive assay. Results: Serum TNFα concentrations were decreased in breachers when compared to control concentrations (p < 0.01). There were no differences in serum concentrations of IL-6, IL-10, or the IL-6/IL-10 ratio between breachers and controls (p's > 0.01). In neuronal-derived EVs, TNFα and IL-6 levels were increased in breachers compared to controls (p's < 0.01), and IL-10 levels were decreased in the breacher group compared to controls (p < 0.01). In breachers the IL-6/IL-10 ratio in neuronal-derived EVs was higher compared to controls, which correlated with higher total Rivermead Post-concussion Questionnaire (RPQ) scores (p's < 0.05). Conclusions: These findings suggest that exposure of personnel to high numbers of low-level blast over a career may result in enduring central inflammation that is associated with chronic neurological symptoms. The data also suggest that peripheral markers of inflammation are not necessarily adequate surrogates for central neuroinflammation.

A Pilot Study of Whole-Blood Transcriptomic Analysis to Identify Genes Associated with Repetitive Low-Level Blast Exposure in Career Breachers.

Repetitive low-level blast exposure is one of the major occupational health concerns among US military service members and law enforcement. This study seeks to identify gene expression using microRNA and RNA sequencing in whole-blood samples from experienced breachers and unexposed controls. We performed experimental RNA sequencing using Illumina's HiSeq 2500 Sequencing System, and microRNA analysis using NanoString Technology nCounter miRNA expression panel in whole-blood total RNA samples from 15 experienced breachers and 14 age-, sex-, and race-matched unexposed controls. We identified 10 significantly dysregulated genes between experienced breachers and unexposed controls, with FDR corrected <0.05: One upregulated gene, LINC00996 (long intergenic non-protein coding RNA 996); and nine downregulated genes, IGLV3-16 (immunoglobulin lambda variable 3-16), CD200 (CD200 molecule), LILRB5 (leukocyte immunoglobulin-like receptor B5), ZNF667-AS1 (ZNF667 antisense RNA 1), LMOD1 (leiomodin 1), CNTNAP2 (contactin-associated protein 2), EVPL (envoplakin), DPF3 (double PHD fingers 3), and IGHV4-34 (immunoglobulin heavy variable 4-34). The dysregulated gene expressions reported here have been associated with chronic inflammation and immune response, suggesting that these pathways may relate to the risk of lasting neurological symptoms following high exposures to blast over a career.

Obtaining anatomic motion and laxity characteristics in a total knee design.

BACKGROUND: Since the introduction of the first total knee designs, a frequent design goal has been to reproduce normal knee motion. However, studies of many currently used total knee designs, have shown that this goal has not been achieved. We proposed that Guided Motion total knee designs, could achieve more anatomic motion than present standard designs. METHODS: Several Guided Motion knees for application without cruciate ligaments were designed using a computer method where the bearing surfaces were generated by the motion required. A knee testing machine was constructed where physiological forces including compressive, shear and torque were applied during knee flexion. The neutral path of motion and the laxity about the neutral path were measured. This evaluation method was a modification of the ASTM standard Constraint Test. RESULTS: The motions of the Guided Motion knees and a standard PS knee were compared with the anatomic motion of knee specimens determined in an earlier study The Guided Motion knees showed motion patterns which were closer to anatomic than the PS knee. CONCLUSIONS: The results provided justification for carrying out further evaluations of functional conditions, using either knee simulators or computer modelling. If anatomic motions could be reproduced in vivo, it is possible that clinical outcomes could be improved.

Differentiating between viruses and virus species by writing their names correctly.

Following the results of the International Committee on Taxonomy of Viruses (ICTV) Ratification Vote held in March 2021, a standard two-part "binomial nomenclature" is now the norm for naming virus species. Adoption of the new nomenclature is still in its infancy; thus, it is timely to reiterate the distinction between "virus" and "virus species" and to provide guidelines for naming and writing them correctly.