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Rasmus Gregersen,1,2 Cathrine Fox Maule,3 Henriette Husum Bak-Jensen,2 Allan Linneberg,3,4 Olav Wendelboe Nielsen,4,5 Simon Francis Thomsen,6 Christian S Meyhoff,2,4,7 Kim Dalhoff,4,8 Michael Krogsgaard,4,9 Henrik Palm,4,9 Hanne Christensen,4,10 Celeste Porsbjerg,4,11 Kristian Antonsen,12 Jørgen Rungby,2,4,13 Steen B Haugaard,2,4,13 Janne Petersen,3,14 Finn E Nielsen1,2 1Department of Emergency Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 2Copenhagen Center for Translational Research, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 3Center for Clinical Research and Prevention, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 4Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 5Department of Cardiology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 6Department of Dermatology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 7Department of Anaesthesia and Intensive Care, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 8Department of Clinical Pharmacology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 9Department of Orthopedics, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 10Department of Neurology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 11Department of Respiratory Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 12Executive Board, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 13Department of Endocrinology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 14Section of Biostatistics, Department of Public Health, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Rasmus Gregersen, Department of Emergency Medicine, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, NV, 2400, Denmark, Email rasmus.gregersen@regionh.dkPurpose: To present a metropolitan cohort, Bispebjerg acute cohort (BAC), and compare patient characteristics and outcomes with patients from urban and rural hospitals in Denmark.Patients and Methods: We linked data from seven Danish nationwide registries and included all acute contacts to non-psychiatric hospitals in the years 2016– 2018. Acute hospital contacts to Bispebjerg and Frederiksberg Hospital constituted BAC, representing a solely metropolitan/urban catchment area. Patient characteristics and outcomes were compared to the rest of Denmark in an urban cohort (UrC) and a rural cohort (RuC), stratified by visit and hospitalization contact types.Results: We identified 4,063,420 acute hospital contacts in Denmark and BAC constituted 8.4% (n=343,200) of them. BAC had a higher proportion of visits (65.1%) compared with UrC (52.1%) and RuC (45.3%). Patients in BAC more often lived alone (visits: BAC: 34.8%, UrC: 30.6%, RuC: 29.2%; hospitalizations: BAC: 50.8%, UrC: 36.7%, RuC: 37.2%) and had temporary CPR number (visits: BAC: 4.4%, UrC: 1.9%, RuC: 1.6%; hospitalizations: BAC: 1.5%, UrC: 0.9%, RuC: 0.8%). Visit patients in BAC were younger (BAC: 36, UrC: 42, RuC: 45 years, median), more often students (BAC: 18.0%, UrC: 14.0%, RuC: 12.5%), and had more contacts due to infectious diseases (BAC: 19.8%, UrC: 14.1%, RuC: 6.2%) but less due to injuries (BAC: 40.0%, UrC: 43.8%, RuC: 60.7%). Hospitalized patients in BAC had higher median age (BAC: 64, UrC: 61, RuC: 64 years) and fewer were in employment than in UrC (BAC: 26.1%, UrC: 32.1%, RuC: 28.1%). BAC Hospitalizations had a lower death rate within 30 days than in RuC (BAC: 3.0% [2.9– 3.1%], UrC: 3.1% [3.0– 3.1%], RuC: 3.4% [3.3– 3.4%]), but a higher readmission-rate (BAC: 20.5% [20.3– 20.8%], UrC: 17.3% [17.2– 17.4%], RuC: 17.5% [17.5– 17.6%]).Conclusion: Significant differences between BAC, urban, and rural cohorts may be explained by differences in healthcare structure and sociodemographics of the catchment areas.Keywords: emergency medicine, acute care, urban-rural disparities, registry-based research, Danish national registers, epidemiology

OBJECTIVE: To determine whether children aged 3-59 months with mild or non-symptomatic human immunodeficiency virus (HIV) infection and WHO-defined severe pneumonia have a higher failure rate than do HIV-uninfected children when treated with the standard WHO treatment of parenteral penicillin or oral amoxicillin. METHODS: This study was a planned sub-analysis of a randomized trial of 3-59-month-old children presenting with WHO-defined severe pneumonia (the APPIS study). We included two sites with high HIV prevalence in Durban, South Africa and Ndola, Zambia. Primary outcome measures were clinical treatment failure at day 2 and day 14. CLINICALTRIALS.GOV IDENTIFIER: CT00227331http://www.clinicaltrialsgov/show/NCT00227331). FINDINGS: Of the 523 children enrolled, HIV status was known for 464 participants; 106 (23%) of these were infected with HIV. By day 2, 57 (12.3%) children had failed treatment and 110 (23.7%) failed by day 14. Twenty (18.9%) HIV-infected children failed by day 2 compared with 37 (10.3%) uninfected children (adjusted odds ratio (OR) 2.07; 95% confidence interval (CI): 1.07-4.00). Thirty-four (32.1%) HIV-infected children failed treatment by day 14 compared with 76 (21.2%) uninfected children (adjusted OR 1.88; 95% CI: 1.11-3.17). Analysis stratified by age showed that the greatest differential in treatment failure at day 2 and day 14 occurred in the children aged 3-5 months. CONCLUSIONS: HIV-infected children with severe pneumonia fail WHO-standard treatment with parenteral penicillin or amoxicillin at day 2 and day 14 more often than do HIV-uninfected children, especially young infants. Standard case management of acute respiratory infection (ARI) using WHO treatment guidelines is inadequate in areas of high HIV prevalence and reappraisal of empiric antimicrobial therapy is urgently needed for severe pneumonia associated with HIV-1.

Abstract Background Communication impairment is a frequent consequence of stroke. Patients who cannot articulate their needs respond with frustration and agitation, resulting in poor optimization of post-stroke functions. A key component of patient-centred care is the ability of staff to communicate in a way that allows them to understand the patient’s needs. We developed a patient-centred communication intervention targeting registered and unregulated nursing staff caring for complex continuing care patients with communication impairments post stroke. Research objectives include 1) examining the effects of the intervention on patients’ quality of life, depression, satisfaction with care, and agitation; and (2) examining the extent to which the intervention improves staff’s attitudes and knowledge in caring for patients with communication impairments. The intervention builds on a previous pilot study. Methods/design A quasi-experimental repeated measures non-equivalent control group design in a complex continuing care facility is being used. Patients with a communication impairment post-stroke admitted to the facility are eligible to participate. All staff nurses are eligible. Baseline data are collected from staff and patients. Follow-up will occur at 1 and 3 months post-intervention. Subject recruitment and data collection from 60 patients and 30 staff will take approximately 36 months. The Patient-Centred Communication Intervention consists of three components: (1) development of an individualized patient communication care plan; (2) a one-day workshop focused on communication and behavioural management strategies for nursing staff; and (3) a staff support system. The intervention takes comprehensive patient assessments into account to inform the development of communication and behavioural strategies specifically tailored to each patient. Discussion The Patient-Centred Communication Intervention will provide staff with strategies to facilitate interactions with patients and to minimize agitation associated with considerable stress. The improvement of these interactions will lead to a reduction of agitation, which has the additional significance of increasing patients’ well-being, quality of life, and satisfaction with care. Trial registration ClinicalTrials.gov Identifier NCT01654029

Abstract Background Methylmercury (MeHg) is a neurotoxin primarily found in seafood; exposures in reproductive-age women are of concern due to vulnerability of the developing fetus. MeHg is mainly eliminated via an enterohepatic cycle involving the liver and gallbladder. Dysfunction in these organs has been associated with slower MeHg elimination in laboratory animals. We hypothesized that women testing positive for chronic hepatitis B (HBV) or C (HCV), both associated with risk of longer-term liver and gallbladder impairment, would have higher total blood mercury (TBHg) concentrations than those negative for the viruses, reflecting slower MeHg elimination. Methods Geometric mean (GM) TBHg levels from a representative sample of over 5,000 seafood-consuming, reproductive-age women from eight years (2001–2008) of the US NHANES survey were compared by viral hepatitis status (as determined by serological assay) using multiple linear regression. Adjustment was made for estimated MeHg intake from seafood consumption, social and demographic variables and other predictors. Results Women with chronic HBV had 1.52 (95% CI 1.13, 2.05, p Conclusions While study design prevents inferences on causality, the finding that MeHg biomarkers differ by hepatitis status in this population suggests viral hepatitis may alter the pace of MeHg elimination. Offspring of HBV-infected seafood-consuming women may be at higher risk of MeHg-induced developmental delays than offspring of those uninfected. Possible reasons for the unanticipated negative association with HCV are explored.

Abstract Background Kaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV) infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART) and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV. Results We analyzed cross-sectional data collected from 404 HIV-infected treatment-naïve adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa between November 2008 and March 2009. Subjects were screened at ART initiation for antibodies to KSHV lytic K8.1 and latent Orf73 antigens. Seropositivity to KSHV was defined as positive to either lytic KSHV K8.1 or latent KSHV Orf73 antibodies. KSHV viremia was determined by quantitative PCR and CD3, 4 and 8 lymphocyte counts were determined with flow cytometry. Of the 404 participants, 193 (48%) tested positive for KSHV at ART initiation; with 76 (39%) reactive to lytic K8.1, 35 (18%) to latent Orf73 and 82 (42%) to both. One individual presented with clinical KS at ART initiation. The KSHV infected group was similar to those without KSHV in terms of age, race, gender, ethnicity, smoking and alcohol use. KSHV infected individuals presented with slightly higher median CD3 (817 vs. 726 cells/mm3) and CD4 (90 vs. 80 cells/mm3) counts than KSHV negative subjects. We found no associations between KSHV seropositivity and body mass index, tuberculosis status, WHO stage, HIV RNA levels, full blood count or liver function tests at initiation. Those with detectable KSHV viremia (n = 19), however, appeared to present with signs of more advanced HIV disease including anemia and WHO stage 3 or 4 defining conditions compared to those in whom the virus was undetectable. Conclusions We demonstrate a high prevalence of KSHV among HIV-infected adults initiating ART in a large urban public-sector HIV clinic. KSHV viremia but not KSHV seropositivity may be associated with markers of advanced HIV disease.

Abstract Background As access to antiretroviral therapy (ART) has grown in Africa, attention has turned to evaluating the socio-economic impacts of ART. One key issue is the extent to which improvements in health resulting from ART allows individuals to return to work and earn income. Improvements in health from ART may also be associated with reduced impaired presenteeism, which is the loss of productivity when an ill or disabled individual attends work but accomplishes less at his or her usual tasks or shifts to other, possibly less valuable, tasks. Methods Longitudinal data for this analysis come from company payroll records for 97 HIV-infected tea estate workers (the index group, 56 women, 41 men) and a comparison group of all workers assigned to the same work teams (n = 2485, 1691 men, 794 women) for a 37-month period covering two years before and one year after initiating ART. We used nearest neighbour matching methods to estimate the impacts of HIV/AIDS and ART on three monthly employment outcomes for tea estate workers in Kenya – days plucking tea, days assigned to non-plucking assignments, and kilograms harvested when plucking. Results The female index group worked 30% fewer days plucking tea monthly than the matched female comparison group during the final 9 months pre-ART. They also worked 87% more days on non-plucking assignments. While the monthly gap between the two groups narrowed after beginning ART, the female index group worked 30% fewer days plucking tea and about 100% more days on non-plucking tasks than the comparison group after one year on ART. The male index group was able to maintain a similar pattern of work as their comparison group except during the initial five months on therapy. Conclusion Significant impaired presenteeism continued to exist among the female index group after one year on ART. Future research needs to explore further the socio-economic implications of HIV-infected female workers on ART being less productive than the general female workforce over sustained periods of time.

We propose a new approach to reduce speckle noise and enhance structures in speckle-corrupted images. It utilizes a median-anisotropic diffusion compound scheme. The median-filter-based reaction term acts as a guided energy source to boost the structures in the image being processed. In addition, it regularizes the diffusion equation to ensure the existence and uniqueness of a solution. We also introduce a decimation and back reconstruction scheme to further enhance the processing result. Before the iteration of the diffusion process, the image is decimated and a subpixel shifted image set is formed. This allows a multichannel parallel diffusion iteration, and more importantly, the speckle noise is broken into impulsive or salt-pepper noise, which is easy to remove by median filtering. The advantage of the proposed technique is clear when it is compared to other diffusion algorithms and the well-known adaptive weighted median filtering (AWMF) scheme in both simulation and real medical ultrasound images.

The chiral iridium rotors Ir(ppy) 2 (pyX)Cl (X = CC-SiR 3 , R = alkyl) remarkably contain two distinct rotational conformers in the ground (S 0 ) and excited (T 1 ) states that can be detected by NMR and emission measurements respectively at variable temperatures. The observed phosphorescent emissions, vibronic (involving L = ppy) and broad (L = pyX), arise from different triplet ligand to metal charge transfers from the two rotational conformers at distinct 3 MLCT excited states. Both conformers exist in these Ir(ppy) 2 (pyX)Cl rotors due to the electron-withdrawing, conjugated substituent X.

The benefits of social living are well established, but sociality also comes with costs, including infectious disease risk. This cost-benefit ratio of sociality is expected to change across individuals' lifespans, which may drive changes in social behaviour with age. To explore this idea, we combine data from a group-living primate for which social ageing has been described with epidemiological models to show that having lower social connectedness when older can protect against the costs of a hypothetical, directly transmitted endemic pathogen. Assuming no age differences in epidemiological characteristics (susceptibility to, severity, and duration of infection), older individuals suffered lower infection costs, which was explained largely because they were less connected in their social networks than younger individuals. This benefit of 'social ageing' depended on epidemiological characteristics and was greatest when infection severity increased with age. When infection duration increased with age, social ageing was beneficial only when pathogen transmissibility was low. Older individuals benefited most from having a lower frequency of interactions (strength) and network embeddedness (closeness) and benefited less from having fewer social partners (degree). Our study provides a first examination of the epidemiology of social ageing, demonstrating the potential for pathogens to influence evolutionary dynamics of social ageing in natural populations.

Background: Despite a growing body of literature regarding anterior cruciate ligament reconstruction (ACLR), there remains a wide diversity in surgical technique and clinical practice across providers., Purpose: To (1) describe current ACLR practice preferences among members of the Herodicus society and (2) determine whether these preferences are influenced by years in practice and overall surgical volume., Study Design: Cross-sectional study., Methods: A 24-question survey investigating surgeons' practices and preferred ACLR surgical techniques was sent via email to all active Herodicus Society members. Survey responses were subdivided by years of experience and overall ACLR annual case volume. Descriptive statistics were compiled and chi-square testing was utilized to determine the significance of experience and case volume on survey responses., Results: Of the 113 invited Herodicus Society members who perform ACLR, 69 (61%) completed the survey. Respondents had a mean ± SD of 30.9 ± 9.8 years of experience in clinical practice and performed a mean of 96.0 ± 50.7 primary and 21.6 ± 16.9 revision ACLR annually. Of revision cases, 72.1% were performed using a single-stage technique. Mean frequency of graft usage by surgeon was bone-patellar tendon-bone autograft (58.6%), quadriceps autograft (14.6%), hamstring tendon autograft (14.0%), and allograft (11.8%). The plurality of surgeons responded that they used anterolateral augmentation "rarely" in primary ACLR (39.1%) and "sometimes" in revision ACLR (31.9%), with the majority performing lateral extra-articular tenodesis (66.7%) rather than anterolateral ligament reconstruction (14.5%). Most surgeons would not allow a 20-year-old football player to return before 7 months after ACLR (71.0%) but highly valued return-to-sports testing to determine readiness (94.2%). Higher volume surgeons performed single-stage revision ACLR at a significantly higher rate (79.8% vs 62.9%, P = .02) and significantly differed in return-to-sports criteria, with a greater proportion relying primarily on biometric testing ( P = .01)., Conclusion: The survey demonstrated that, in the Herodicus Society, a wide range of preferences exist regarding ACLR surgical technique. Bone-patellar tendon-bone autograft is the most frequent primary ACLR graft choice. Most participants have not embraced newer techniques such as anterolateral or suture tape augmentation. Return to sports is generally not allowed before 7 months and heavily factors-in return-to-sports testing metrics, suggesting that purely time-based criteria for return to sports is not modern practice among elite sports medicine surgeons., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: I.D.E. has received education payments from Arthrex, Mid-Atlantic Surgical Systems, Smith+Nephew; hospitality payments from Stryker; and a grant from Arthrex. M.A.F. has received education payments from Mid-Atlantic Surgical Systems. A.J.C. has received education payments from Arthrex, Medwest Associates, Mid-Atlantic Surgical Systems, Smith+Nephew, Supreme Orthopedic Systems; hospitality payments from Stryker; and a grant from Arthrex. J.W.A. has received education payments from Mid-Atlantic Surgical Systems; hospitality payments from Arthrex, Mid-Atlantic Surgical Systems, Smith+Nephew; and grants from Arthrex and DJO. V.M. has received nonconsulting fees from Smith & Nephew and Synthes GmbH; and consulting fees from Smith & Nephew. J.P.B. has received consulting fees from Arthrex and DJO; nonconsulting fees from Arthrex; royalties from Arthrex; and education payments from Fones Marketing Management. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2024.)

The apicomplexan parasite Toxoplasma gondii has developed mechanisms to establish a central nervous system infection in virtually all warm-blooded animals. Acute T. gondii infection can cause neuroinflammation, encephalitis, and seizures. Meanwhile, studies in humans, nonhuman primates, and rodents have linked chronic T. gondii infection with altered behavior and increased risk for neuropsychiatric disorders, including schizophrenia. These observations and associations raise questions about how this parasitic infection may alter neural circuits. We previously demonstrated that T. gondii infection triggers the loss of inhibitory perisomatic synapses, a type of synapse whose dysfunction or loss has been linked to neurological and neuropsychiatric disorders. We showed that phagocytic cells (including microglia and infiltrating monocytes) contribute to the loss of these inhibitory synapses. Here, we show that these phagocytic cells specifically ensheath excitatory pyramidal neurons, leading to the preferential loss of perisomatic synapses on these neurons and not those on cortical interneurons. Moreover, we show that infection induces an increased expression of the complement C3 gene, including by populations of these excitatory neurons. Infecting C3-deficient mice with T. gondii revealed that C3 is required for the loss of perisomatic inhibitory synapses. Interestingly, loss of C1q did not prevent the loss of perisomatic synapses following infection. Together, these findings provide evidence that T. gondii induces changes in excitatory pyramidal neurons that trigger the selective removal of inhibitory perisomatic synapses and provide a role for a nonclassical complement pathway in the remodeling of inhibitory circuits in the infected brain., (© 2023 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Retinal ganglion cell (RGC) axons provide direct input into several brain regions, including the dorsal lateral geniculate nucleus (dLGN), which is important for image-forming vision, and the ventrolateral geniculate nucleus (vLGN), which is associated with nonimage-forming vision. Through both activity- and morphogen-dependent mechanisms, retinal inputs play important roles in the development of dLGN, including the refinement of retinal projections, morphological development of thalamocortical relay cells (TRCs), timing of corticogeniculate innervation, and recruitment and distribution of inhibitory interneurons. In contrast, little is known about the role of retinal inputs in the development of vLGN. Grossly, vLGN is divided into two domains, the retinorecipient external vLGN (vLGNe) and nonretinorecipient internal vLGN (vLGNi). Studies previously found that vLGNe consists of transcriptionally distinct GABAergic subtypes distributed into at least four adjacent laminae. At present, it remains unclear whether retinal inputs influence the development of these cell-type-specific neuronal laminae in vLGNe. Here, we elucidated the developmental timeline for these laminae in the mouse vLGNe, and results indicate that these laminae are specified at or before birth. We observed that mutant mice without retinal inputs have a normal laminar distribution of GABAergic cells at birth; however, after the first week of postnatal development, these mutants exhibited a dramatic disruption in the laminar organization of inhibitory neurons and clear boundaries between vLGNe and vLGNi. Overall, our results show that while the formation of cell-type-specific layers in mouse vLGNe does not depend on RGC inputs, retinal signals are critical for their maintenance., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Stebbins et al.)

The efficiency of thermally activated delayed fluorescence (TADF) in organic materials relies on rapid intersystem crossing rates and fast conversion of triplet (T) excitons into a singlet (S) state. Heavy atoms such as sulfur or selenium are now frequently incorporated into TADF molecular structures to enhance these properties by increased spin-orbit coupling [spin orbit coupling (SOC)] between the T and S states. Here a series of donor-acceptor (D-A) molecules based on 12 H -benzo[4,5]thieno[2,3- a ]carbazole and dicyanopyridine is compared with their nonsulfur control molecules designed to probe such SOC effects. We reveal that unexpected intermolecular interactions of the D-A molecules with carbazole-containing host materials instead serve as the dominant pathway for triplet decay kinetics in these materials. In-depth photophysical and computational studies combined with organic light emitting diode measurements demonstrate that the anticipated heavy-atom effect from sulfur is overshadowed by exciplex formation. Indeed, even the unsubstituted acceptor fragments exhibit pronounced TADF exciplex emission in appropriate carbazole hosts. The intermolecular charge transfer and TADF in these systems are further confirmed by detailed time-dependent density functional theory studies. This work demonstrates that anticipated heavy-atom effects in TADF emitters do not always control or even impact the photophysical and electroluminescence properties., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Coronal and sagittal plane knee malalignments have been shown to increase the forces on anterior cruciate ligament (ACL) grafts after ACL reconstruction (ACLR). Studies have shown the benefit of high tibial osteotomy to address coronal and sagittal imbalance in revision ACLR. The purpose of this article is to further describe the use of osteotomy by reviewing preoperative planning, indications, techniques, and outcomes of high tibial opening and closing wedge as well as anterior tibial closing wedge osteotomies in the setting of ACLR., Competing Interests: Disclosure The authors have no relevant commercial or financial conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Icosahedral carboranes, C 2 B 10 H 12 , have long been considered to be aromatic but the extent of conjugation between these clusters and their substituents is still being debated. m- and p-Carboranes are compared with m- and p-phenylenes as conjugated bridges in optical functional chromophores with a donor and an acceptor as substituents here. The absorption and fluorescence data for both carboranes from experimental techniques (including femtosecond transient absorption, time-resolved fluorescence and broadband fluorescence upconversion) show that the absorption and emission processes involve strong intramolecular charge transfer between the donor and acceptor substituents via the carborane cluster. From quantum chemical calculations on these carborane systems, the charge transfer process depends on the relative torsional angles of the donor and acceptor groups where an overlap between the two frontier orbitals exists in the bridging carborane cluster., (© 2024. The Author(s).)

Increasing age is associated with dysregulated immune function and increased inflammation-patterns that are also observed in individuals exposed to chronic social adversity. Yet we still know little about how social adversity impacts the immune system and how it might promote age-related diseases. Here, we investigated how immune cell diversity varied with age, sex and social adversity (operationalized as low social status) in free-ranging rhesus macaques. We found age-related signatures of immunosenescence, including lower proportions of CD20 + B cells, CD20 + /CD3 + ratio, and CD4 + /CD8 + T cell ratio - all signs of diminished antibody production. Age was associated with higher proportions of CD3 + /CD8 + Cytotoxic T cells, CD16 + /CD3- Natural Killer cells, CD3 + /CD4 + /CD25 + and CD3 + /CD8 + /CD25 + T cells, and CD14 + /CD16 + /HLA-DR + intermediate monocytes, and lower levels of CD14 + /CD16-/HLA-DR + classical monocytes, indicating greater amounts of inflammation and immune dysregulation. We also found a sex-dependent effect of exposure to social adversity (i.e., low social status). High-status males, relative to females, had higher CD20 + /CD3 + ratios and CD16 + /CD3 Natural Killer cell proportions, and lower proportions of CD8 + Cytotoxic T cells. Further, low-status females had higher proportions of cytotoxic T cells than high-status females, while the opposite was observed in males. High-status males had higher CD20 + /CD3 + ratios than low-status males. Together, our study identifies the strong age and sex-dependent effects of social adversity on immune cell proportions in a human-relevant primate model. Thus, these results provide novel insights into the combined effects of demography and social adversity on immunity and their potential contribution to age-related diseases in humans and other animals., (© 2023. The Author(s), under exclusive licence to American Aging Association.)

The mouse retina contains over 40 types of retinal ganglion cells (RGCs) that differ in morphology, function, or gene expression. RGCs also differ by whether their axons target the brain.s ipsilateral or contralateral hemisphere. Contralaterally projecting RGCs (contraRGCs) are widespread in mouse retina, whereas ipsilateral projecting RGCs (ipsiRGCs) are confined to the ventro-temporal (VT) crescent of retina. In this study, we employed the Sert-Cre transgenic line, which had been reported to selectively label ipsiRGCs, to study ipsiRGCs during development. Although the number of Cre-expressing ipsiRGCs did not significantly increase with postnatal age, the region of retina that they occupied did, and by adulthood represented ~30% of the retinal surface. Unexpectedly, genetic ablation of Sert-Cre cells failed to fully disrupt ipsilateral projecting retinal axons, suggesting that not all ipsiRGCs generated Cre in Sert-Cre mice. To test this hypothesis, we retrogradely labeled ipsiRGCs in Sert-Cre mice which revealed that not all ipsiRGCs are labeled in Sert-Cre mice and a small population of contraRGCs flanking the VT crescent generates Cre in this line. These results do not negate the usefulness of the Sert-Cre mouse but do raise important caveats to the interpretation of such studies., (© 2024 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.)

Background: The glenoid track concept for shoulder instability primarily describes the medial-lateral relationship between a Hill-Sachs lesion and the glenoid. However, the Hill-Sachs position in the craniocaudal dimension has not been thoroughly studied., Hypothesis: Hill-Sachs lesions with greater inferior extension are associated with increased risk of recurrent instability after primary arthroscopic Bankart repair., Study Design: Case-control study; Level of evidence, 3., Methods: The authors performed a retrospective analysis of patients with on-track Hill-Sachs lesions who underwent primary arthroscopic Bankart repair (without remplissage) between 2007 and 2019 and had a minimum 2-year follow-up. Recurrent instability was defined as recurrent dislocation or subluxation after the index procedure. The craniocaudal position of the Hill-Sachs lesion was measured against the midhumeral axis on sagittal magnetic resonance imaging (MRI) using either a Hill-Sachs bisecting line through the humeral head center (sagittal midpoint angle [SMA], a measure of Hill-Sachs craniocaudal position) or a line tangent to the inferior Hill-Sachs edge (lower-edge angle [LEA], a measure of Hill-Sachs caudal extension). Univariate and multivariate regression were used to determine the predictive value of both SMA and LEA for recurrent instability., Results: In total, 176 patients were included with a mean age of 20.6 years, mean follow-up of 5.9 years, and contact sport participation of 69.3%. Of these patients, 42 (23.9%) experienced recurrent instability (30 dislocations, 12 subluxations) at a mean time of 1.7 years after surgery. Recurrent instability was found to be significantly associated with LEA >90° (ie, Hill-Sachs lesions extending below the humeral head equator), with an OR of 3.29 ( P = .022). SMA predicted recurrent instability to a lesser degree (OR, 2.22; P = .052). Post hoc evaluation demonstrated that LEA >90° predicted recurrent dislocations (subset of recurrent instability) with an OR of 4.80 ( P = .003). LEA and SMA were found to be collinear with Hill-Sachs interval and distance to dislocation, suggesting that greater LEA and SMA proportionally reflect lesion severity in both the craniocaudal and medial-lateral dimensions., Conclusion: Inferior extension of an otherwise on-track Hill-Sachs lesion is a highly predictive risk factor for recurrent instability after primary arthroscopic Bankart repair. Evaluation of Hill-Sachs extension below the humeral equator (inferior equatorial extension) on sagittal MRI is a clinically facile screening tool for higher-risk lesions with subcritical glenoid bone loss. This threshold for critical humeral bone loss may inform surgical stratification for procedures such as remplissage or other approaches for at-risk on-track lesions., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: T.C. has received a grant from Arthrex and support for education from Mid-Atlantic Surgical Systems. M.F. has received support for education from Mid-Atlantic Surgical Systems. A.B. has received support for education from CGG Medical, Mid-Atlantic Surgical Systems, Smith + Nephew, Fortis Surgical, Supreme Orthopedic Systems, and Arthrex; grants from Encore Medical and Arthrex; and hospitality payments from Stryker. B.L. has received support for education from Mid-Atlantic Surgical Systems. M.R. has received support for education from Mid-Atlantic Surgical Systems. A.L. has received consulting fees from Arthrex, Tornier, Stryker, and Wright Medical Technology; and support for education from Mid-Atlantic Surgical Systems. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

BACKGROUND. Precontrast CT is an established means of evaluating for hepatic steatosis; postcontrast CT has historically been limited for this purpose. OBJECTIVE. The purpose of this study was to evaluate the diagnostic performance of portal venous phase postcontrast CT in detecting at least moderate hepatic steatosis using liver and spleen attenuation measurements determined by an automated artificial intelligence (AI) tool. METHODS. This retrospective study included 2917 patients (1381 men, 1536 women; mean age, 56.8 years) who underwent a CT examination that included at least two series through the liver. Examinations were obtained from an AI vendor's data lake of data from 24 centers in one U.S. health care network and 29 centers in one Israeli health care network. An automated deep learning tool extracted liver and spleen attenuation measurements. The reference for at least moderate steatosis was precontrast liver attenuation of less than 40 HU (i.e., estimated liver fat > 15%). A radiologist manually reviewed examinations with outlier AI results to confirm portal venous timing and identify issues impacting attenuation measurements. RESULTS. After outlier review, analysis included 2777 patients with portal venous phase images. Prevalence of at least moderate steatosis was 13.9% (387/2777). Patients without and with at least moderate steatosis, respectively, had mean postcontrast liver attenuation of 104.5 ± 18.1 (SD) HU and 67.1 ± 18.6 HU ( p < .001); a mean difference in postcontrast attenuation between the liver and the spleen (hereafter, postcontrast liver-spleen attenuation difference) of -7.6 ± 16.4 (SD) HU and -31.8 ± 20.3 HU ( p < .001); and mean liver enhancement of 49.3 ± 15.9 (SD) HU versus 38.6 ± 13.6 HU ( p < .001). Diagnostic performance for the detection of at least moderate steatosis was higher for postcontrast liver attenuation (AUC = 0.938) than for the postcontrast liver-spleen attenuation difference (AUC = 0.832) ( p < .001). For detection of at least moderate steatosis, postcontrast liver attenuation had sensitivity and specificity of 77.8% and 93.2%, respectively, at less than 80 HU and 90.5% and 78.4%, respectively, at less than 90 HU; the postcontrast liver-spleen attenuation difference had sensitivity and specificity of 71.4% and 79.3%, respectively, at less than -20 HU and 87.0% and 62.1%, respectively, at less than -10 HU. CONCLUSION. Postcontrast liver attenuation outperformed the postcontrast liver-spleen attenuation difference for detecting at least moderate steatosis in a heterogeneous patient sample, as evaluated using an automated AI tool. Splenic attenuation likely is not needed to assess for at least moderate steatosis on postcontrast images. CLINICAL IMPACT. The technique could promote early detection of clinically significant nonalcoholic fatty liver disease through individualized or large-scale opportunistic evaluation.