Towards a standardized framework for AI-assisted, image-based monitoring of nocturnal insects.

Automated sensors have potential to standardize and expand the monitoring of insects across the globe. As one of the most scalable and fastest developing sensor technologies, we describe a framework for automated, image-based monitoring of nocturnal insects-from sensor development and field deployment to workflows for data processing and publishing. Sensors comprise a light to attract insects, a camera for collecting images and a computer for scheduling, data storage and processing. Metadata is important to describe sampling schedules that balance the capture of relevant ecological information against power and data storage limitations. Large data volumes of images from automated systems necessitate scalable and effective data processing. We describe computer vision approaches for the detection, tracking and classification of insects, including models built from existing aggregations of labelled insect images. Data from automated camera systems necessitate approaches that account for inherent biases. We advocate models that explicitly correct for bias in species occurrence or abundance estimates resulting from the imperfect detection of species or individuals present during sampling occasions. We propose ten priorities towards a step-change in automated monitoring of nocturnal insects, a vital task in the face of rapid biodiversity loss from global threats. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

Turbidimetric bioassays: A solution to antimicrobial activity detection in asymptomatic bacteriuria isolates against uropathogenic Escherichia coli.

Traditional bacteriocin screening methods often face limitations due to diffusion-related challenges in agar matrices, which can prevent the peptides from reaching their target organism. Turbidimetric techniques offer a solution to these issues, eliminating diffusion-related problems and providing an initial quantification of bacteriocin efficacy in producer organisms. This study involved screening the cell-free supernatant (CFS) from eight uncharacterized asymptomatic bacteriuria (ABU) isolates and Escherichia coli 83972 for antimicrobial activity against clinical uropathogenic E. coli (UPEC) strains using turbidimetric growth methods. ABU isolates exhibiting activity against five or more UPEC strains were further characterized (PUTS 37, PUTS 58, PUTS 59, S-07-4, and SK-106-1). The inhibition of the CFS by proteinase K suggested that the antimicrobial activity was proteinaceous in nature, potentially bacteriocins. The activity of E. coli PUTS 58 and SK-106-1 was enhanced in an artificial urine medium, with both inhibiting all eight UPECs. A putative microcin H47 operon was identified in E. coli SK-106-1, along with a previously identified microcin V and colicin E7 in E. coli PUTS 37 and PUTS 58, respectively. These findings indicate that ABU bacteriocin-producers could serve as viable prophylactics and therapeutics in the face of increasing antibiotic resistance among uropathogens.

Monocyte to macrophage differentiation and changes in cellular redox homeostasis promote cell type-specific HIV latency reactivation.

HIV latency regulation in monocytes and macrophages can vary according to signals directing differentiation, polarization, and function. To investigate these processes, we generated an HIV latency model in THP-1 monocytes and showed differential levels of HIV reactivation among clonal populations. Monocyte-to-macrophage differentiation of HIV-infected primary human CD14+ and THP-1 cells induced HIV reactivation and showed that virus production increased concomitant with macrophage differentiation. We applied the HIV-infected THP-1 monocyte-to-macrophage (MLat) model to assess the biological mechanisms regulating HIV latency dynamics during monocyte-to-macrophage differentiation. We pinpointed protein kinase C signaling pathway activation and Cyclin T1 upregulation as inherent differentiation mechanisms that regulate HIV latency reactivation. Macrophage polarization regulated latency, revealing proinflammatory M1 macrophages suppressed HIV reactivation while anti-inflammatory M2 macrophages promoted HIV reactivation. Because macrophages rely on reactive-oxygen species (ROS) to exert numerous cellular functions, we disrupted redox pathways and found that inhibitors of the thioredoxin (Trx) system acted as latency-promoting agents in T-cells and monocytes, but opposingly acted as latency-reversing agents in macrophages. We explored this mechanism with Auranofin, a clinical candidate for reducing HIV reservoirs, and demonstrated Trx reductase inhibition led to ROS induced NF-κB activity, which promoted HIV reactivation in macrophages, but not in T-cells and monocytes. Collectively, cell type-specific differences in HIV latency regulation could pose a barrier to HIV eradication strategies.

Investigations into Increased Incidence of Severe Gizzard Erosions and Ulcerations in U.S. Commercial Broilers.

During a series of pathology surveys in four production complexes of a U.S. broiler integrator, the technical services veterinarians of an animal health company noted a high incidence of severe gizzard erosions and ulcerations (GEU), prompting further clinical investigation and a battery trial. No growth-promoting antibiotics or ionophore coccidiostats were used during the period of these surveys. All used tribasic copper chloride (TBCC) at ≤120 ppm added copper in broiler rations. Clostridium perfringens was isolated from 83% and 67% of gizzard lesions cultured in two complexes, and cecal C. perfringens most probable number determinations were higher in severely affected than in mildly affected or unaffected birds. Histopathology revealed both acellular koilin fusion defects characteristic of copper toxicity, as well as inflammatory cell infiltrates. Intralesional bacilli suggestive of C. perfringens were noted in 78% of affected flocks examined. Species E Aviadenovirus was isolated from one bird in one complex, and that bird had a single intranuclear inclusion body; no other flocks had Adenoviruses isolated or detected on PCR, nor any inclusion bodies. Other viruses detected were thought to be incidental. A pilot study using feed with supplemental copper from TBCC or copper sulfate and challenge with one of the isolated C. perfringens strains reproduced the lesions. A battery study was conducted with an unchallenged negative control group fed a diet with 16 ppm added copper, a group fed the control diet and orally challenged with 108 organisms of a field strain of C. perfringens at 21 and 22 days, and a group treated with the same diet containing 250 ppm added copper from TBCC and orally challenged with C. perfringens. Birds were necropsied at 23 and 28 days. All challenged groups developed lesions, with those receiving both TBCC and C. perfringens having significantly higher gross and histopathological lesion scores than the unchallenged negative controls. Lesions were qualitatively similar to those in the field and contained suspected C. perfringens bacilli. Because the levels of TBCC used in the commercial birds and in the battery trial generally have been considered safe, and because C. perfringens is usually regarded as a pathogen of the lower GI tract, the possible association of these two agents with GEU is a novel observation and warrants further investigation.

Investigaciones sobre el aumento de la incidencia de erosiones y ulceraciones severas en la molleja en pollos de engorde comerciales en los Estados Unidos. Durante una serie de estudios de patología en cuatro complejos de producción de un integrador de pollos de engorde de los Estados Unidos, veterinarios de servicio técnico de una empresa de salud animal observaron una alta incidencia de erosiones y ulceraciones severas de la molleja (GEU), lo que motivó una mayor investigación clínica y un estudio en batería. Durante el período de estas encuestas no se utilizaron antibióticos promotores del crecimiento ni coccidiostáticos ionóforos. Todos utilizaron cloruro de cobre tribásico (TBCC) con un nivel de ≤120 ppm de cobre agregado en raciones para pollos de engorde. Se aisló Clostridium perfringens del 83% y el 67% de las lesiones de molleja cultivadas en dos complejos, y las determinaciones del número más probable de C. perfringens en los sacos ciegos fueron mayores en aves severamente afectadas que en aves levemente afectadas o no afectadas. La histopatología reveló defectos de fusión de la capa córnea acelular característicos de la toxicidad por cobre, así como infiltrados de células inflamatorias. Se observaron bacilos intralesionales sugestivos de C. perfringens en el 78% de las parvadas afectadas examinadas. La especie Aviadenovirus E se aisló de un ave en un complejo, y esa ave tenía un único cuerpo de inclusión intranuclear; en ninguna otra parvada se aislaron o detectaron adenovirus mediante PCR, ni se observaron cuerpos de inclusión. Se pensó que otros virus detectados fueron incidentales. Un estudio piloto que utilizó alimento con cobre suplementario de cloruro de cobre tribásico o sulfato de cobre y con desafío con una de las cepas aisladas de C. perfringens reprodujo las lesiones. Se realizó un estudio de batería con un grupo de control negativo no desafiado alimentado con una dieta con 16 ppm de cobre agregado, un grupo alimentado con la dieta de control y desafiado por vía oral con 108 organismos de una cepa de campo de C. perfringens a los 21 y 22 días, y un grupo tratado con la misma dieta que contenía 250 ppm de cobre agregado de cloruro de cobre tribásico y desafiados por vía oral con C. perfringens. A las aves se les realizó la necropsia a los 23 y 28 días. Todos los grupos desafiados desarrollaron lesiones, y aquellos que recibieron cloruro de cobre tribásico y C. perfringens tuvieron puntuaciones de lesiones macroscópicas e histopatológicas significativamente más altas que los controles negativos no desafiados. Las lesiones eran cualitativamente similares a las del campo y contenían bacilos sospechosos de C. perfringens. Debido a que los niveles de cloruro de cobre tribásico utilizados en las aves comerciales y en el ensayo en batería generalmente se han considerado seguros, y debido a que C. perfringens generalmente se considera un patógeno del tracto gastrointestinal inferior, la posible asociación de estos dos agentes con erosiones y ulceraciones severas de la molleja es una observación reciente y justifica una mayor investigación.

The Management of Persistent Distal Occlusions after Mechanical Thrombectomy and Thrombolysis: An Inter- and Intrarater Agreement Study.

BACKGROUND AND PURPOSE: The best management of patients with persistent distal occlusion after mechanical thrombectomy with or without IV thrombolysis remains unknown. We sought to evaluate the variability and agreement in decision-making for persistent distal occlusions. MATERIALS AND METHODS: A portfolio of 60 cases was sent to clinicians with varying backgrounds and experience. Responders were asked whether they considered conservative management or rescue therapy (stent retriever, aspiration, or intra-arterial thrombolytics) a treatment option as well as their willingness to enroll patients in a randomized trial. Agreement was assessed using κ statistics. RESULTS: The electronic survey was answered by 31 physicians (8 vascular neurologists and 23 interventional neuroradiologists). Decisions for rescue therapies were more frequent (n = 1116/1860, 60%) than for conservative management (n = 744/1860, 40%; P < .001). Interrater agreement regarding the final management decision was "slight" (κ = 0.12; 95% CI, 0.09-0.14) and did not improve when subgroups of clinicians were studied according to background, experience, and specialty or when cases were grouped according to the level of occlusion. On delayed re-questioning, 23 of 29 respondents (79.3%) disagreed with themselves on at least 20% of cases. Respondents were willing to offer trial participation in 1295 of 1860 (69.6%) cases. CONCLUSIONS: Individuals did not agree regarding the best management of patients with persistent distal occlusion after mechanical thrombectomy and IV thrombolysis. There is sufficient uncertainty to justify a dedicated randomized trial.

Unravelling the genetic basis of Schizophrenia.

Neuronal development is a highly regulated mechanism that is central to organismal function in animals. In humans, disruptions to this process can lead to a range of neurodevelopmental phenotypes, including Schizophrenia (SCZ). SCZ has a significant genetic component, whereby an individual with an SCZ affected family member is eight times more likely to develop the disease than someone with no family history of SCZ. By examining a combination of genomic, transcriptomic and epigenomic datasets, large-scale 'omics' studies aim to delineate the relationship between genetic variation and abnormal cellular activity in the SCZ brain. Herein, we provide a brief overview of some of the key omics methods currently being used in SCZ research, including RNA-seq, the assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and high-throughput chromosome conformation capture (3C) approaches (e.g., Hi-C), as well as single-cell/nuclei iterations of these methods. We also discuss how these techniques are being employed to further our understanding of the genetic basis of SCZ, and to identify associated molecular pathways, biomarkers, and candidate drug targets.

Strain-mode-specific mechanical testing and the interpretation of bone adaptation in the deer calcaneus.

The artiodactyl (deer and sheep) calcaneus is a model that helps in understanding how many bones achieve anatomical optimization and functional adaptation. We consider how the dorsal and plantar cortices of these bones are optimized in quasi-isolation (the conventional view) versus in the context of load sharing along the calcaneal shaft by "tension members" (the plantar ligament and superficial digital flexor tendon). This load-sharing concept replaces the conventional view, as we have argued in a recent publication that employs an advanced analytical model of habitual loading and fracture risk factors of the deer calcaneus. Like deer and sheep calcanei, many mammalian limb bones also experience prevalent bending, which seems problematic because the bone is weaker and less fatigue-resistant in tension than compression. To understand how bones adapt to bending loads and counteract deleterious consequences of tension, it is important to examine both strain-mode-specific (S-M-S) testing (compression testing of bone habitually loaded in compression; tension testing of bone habitually loaded in tension) and non-S-M-S testing. Mechanical testing was performed on individually machined specimens from the dorsal "compression cortex" and plantar "tension cortex" of adult deer calcanei and were independently tested to failure in one of these two strain modes. We hypothesized that the mechanical properties of each cortex region would be optimized for its habitual strain mode when these regions are considered independently. Consistent with this hypothesis, energy absorption parameters were approximately three times greater in S-M-S compression testing in the dorsal/compression cortex when compared to non-S-M-S tension testing of the dorsal cortex. However, inconsistent with this hypothesis, S-M-S tension testing of the plantar/tension cortex did not show greater energy absorption compared to non-S-M-S compression testing of the plantar cortex. When compared to the dorsal cortex, the plantar cortex only had a higher elastic modulus (in S-M-S testing of both regions). Therefore, the greater strength and capacity for energy absorption of the dorsal cortex might "protect" the weaker plantar cortex during functional loading. However, this conventional interpretation (i.e., considering adaptation of each cortex in isolation) is rejected when critically considering the load-sharing influences of the ligament and tendon that course along the plantar cortex. This important finding/interpretation has general implications for a better understanding of how other similarly loaded bones achieve anatomical optimization and functional adaptation.

In Vivo Verification of Electron Paramagnetic Resonance Biodosimetry Using Patients Undergoing Radiation Therapy Treatment.

PURPOSE: Electron paramagnetic resonance (EPR) biodosimetry, used to triage large numbers of individuals incidentally exposed to unknown doses of ionizing radiation, is based on detecting a stable physical response in the body that is subject to quantifiable variation after exposure. In vivo measurement is essential to fully characterize the radiation response relevant to a living tooth measured in situ. The purpose of this study was to verify EPR spectroscopy in vivo by estimating the radiation dose received in participants' teeth. METHODS AND MATERIALS: A continuous wave L-band spectrometer was used for EPR measurements. Participants included healthy volunteers and patients undergoing head and neck and total body irradiation treatments. Healthy volunteers completed 1 measurement each, and patients underwent measurement before starting treatment and between subsequent fractions. Optically stimulated luminescent dosimeters and diodes were used to determine the dose delivered to the teeth to validate EPR measurements. RESULTS: Seventy measurements were acquired from 4 total body irradiation and 6 head and neck patients over 15 months. Patient data showed a linear increase of EPR signal with delivered dose across the dose range tested. A linear least-squares weighted fit of the data gave a statistically significant correlation between EPR signal and absorbed dose (P < .0001). The standard error of inverse prediction (SEIP), used to assess the usefulness of fits, was 1.92 Gy for the dose range most relevant for immediate triage (≤7 Gy). Correcting for natural background radiation based on patient age reduced the SEIP to 1.51 Gy. CONCLUSIONS: This study demonstrated the feasibility of using spectroscopic measurements from radiation therapy patients to validate in vivo EPR biodosimetry. The data illustrated a statistically significant correlation between the magnitude of EPR signals and absorbed dose. The SEIP of 1.51 Gy, obtained under clinical conditions, indicates the potential value of this technique in response to large radiation events.

Lymphoproliferative Disease Virus and Reticuloendotheliosis Virus Detection and Disease in Wild Turkeys (Meleagris gallopavo).

Lymphoproliferative disease virus (LPDV) and reticuloendotheliosis virus (REV) are oncogenic retroviruses that can cause disease in wild and domestic fowl. Lymphoproliferative disease virus infections are common and widespread in Wild Turkeys (Meleagris gallopavo) in the US and east-central Canada, while REV has been detected worldwide in numerous avian host species. We tested tissues (spleen, liver, and/or bone marrow, plus neoplastic tissue, if present) from 172 Wild Turkeys that underwent necropsy from December 2018 through October 2021 for both viruses using PCR. We evaluated demographic, geographic, temporal, and seasonal data by chi-square test of independence and logistic regression for turkeys infected with LPDV and/or REV. At least one of these retroviruses was detected in 80.8% (139/172) of Wild Turkeys from 15 US states, with significantly more turkeys being positive for LPDV (72.1%, 124/172) versus REV (43.6%, 75/172; P<0.001). Both viruses (coinfections) were detected in 34.9% (60/172) of turkeys. Among LPDV-infected turkeys (including coinfections), bone marrow had the highest detection rate (38/58, 65.5%), significantly higher than spleen (30/58, 51.7%) and liver (20/58, 34.5%; P<0.001). In REV-infected turkeys, bone marrow had the highest detection rate (24/58, 41.4%). All three tissues (spleen, liver, bone marrow) concurrently tested positive in most (15/25, 60%) REV-infected turkeys. These results suggest LPDV tissue tropism for bone marrow, whereas REV may have broader tissue tropism. Histopathology consistent with lymphoid proliferation and/or neoplasia characteristic of lymphoproliferative disease was evident in 29/172 (16.9%) turkeys assessed, including two REV-only-infected turkeys. Season was significantly associated with LPDV prevalence (highest in winter); year and season were both significantly associated with REV prevalence (highest in 2020 and winter). These data contribute to optimizing diagnostic strategies that may aid in pathogen monitoring and improve detections to increase our understanding of the potential impacts of these viruses on Wild Turkey populations.

Leaf thermal safety margins decline at hotter temperatures in a natural warming 'experiment' in the Amazon.

The threat of rising global temperatures may be especially pronounced for low-latitude, lowland plant species that have evolved under stable climatic conditions. However, little is known about how these species may acclimate to elevated temperatures. Here, we leveraged a strong, steep thermal gradient along a natural geothermal river to assess the ability of woody plants in the Amazon to acclimate to elevated air temperatures. We measured leaf traits in six common tropical woody species along the thermal gradient to investigate whether individuals of these species: acclimate their thermoregulatory traits to maintain stable leaf temperatures despite higher ambient temperatures; acclimate their photosynthetic thermal tolerances to withstand hotter leaf temperatures; and whether acclimation is sufficient to maintain stable leaf thermal safety margins (TSMs) across different growth temperatures. Individuals of three species acclimated their thermoregulatory traits, and three species increased their thermal tolerances with growth temperature. However, acclimation was generally insufficient to maintain constant TSMs. Notwithstanding, leaf health was generally consistent across growth temperatures. Acclimation in woody Amazonian plants is generally too weak to maintain TSMs at high growth temperatures, supporting previous findings that Amazonian plants will be increasingly vulnerable to thermal stress as temperatures rise.

Antimicrobial Metaphylaxis and its Impact on Health, Performance, Antimicrobial Resistance, and Contextual Antimicrobial Use in High-Risk Beef Stocker Calves.

The objective of this blinded, cluster-randomized, complete block trial was to evaluate the impact of metaphylaxis on health, performance, antimicrobial resistance, and contextual antimicrobial use (AMU) in high-risk beef stocker calves. Calves (n = 155) were randomly assigned to receive either saline or tulathromycin at the time of arrival processing. Deep nasopharyngeal swabs were collected from each calf at arrival and 14 d later. Calves were monitored for bovine respiratory disease (BRD) for 42 d. Body weights were obtained at arrival, days 14, 28, and 42. Contextual antimicrobial use (AMU) was calculated using dose and mass-based metrics. Calves given tulathromycin had a greater average daily gain (0.96 ±â€…0.07 kg vs. 0.82 ±â€…0.07 kg; P = 0.034) and lower prevalence of BRD than controls (17% vs. 40%; P = 0.008). Proportions of calves with BRD pathogens identified at arrival were similar between treatment groups [17%; P = 0.94]. Proportions of calves with BRD pathogens identified at day 14 were lower for calves receiving tulathromycin compared to controls (15% vs. 60%, P < 0.001). Overall, 81% of Pastuerella multocida isolates and 47% of Mannheimia haemolytica isolates were pansusceptible. When measured as regimens per head in, AMU in calves receiving tulathromycin was higher than calves receiving saline (P = 0.01). Under the conditions of this study, metaphylaxis had positive impacts on the health and performance of high-risk beef stocker calves, did not contribute to the selection of resistant bacterial isolates in the nasopharynx of treated cattle, and increased AMU.

In this study, we investigated the impact of metaphyactic antimicrobial administration on health, performance, and antimicrobial use in high-risk beef stocker calves. Our findings demonstrated that metaphylaxis improves performance and has positive effects on animal health and well-being but increases total antimicrobial use. Additionally, our study revealed that metaphylaxis alone does not contribute to the selection of antimicrobial-resistant pathogens in the upper airway of treated cattle.

Autosomal dominant neovascular inflammatory vitreoretinopathy with CAPN5 c.731T > C gene mutation; clinical management of a family cohort and review of the literature.

BACKGROUND: To report a cohort of patients with clinically and genetically diagnosed autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) and showcase the spectrum of the disease utilizing multimodal imaging and genetic testing. Additionally, the utility of multimodal imaging in guiding treatment will also be illustrated. MATERIALS/METHODS: Five patients from a single-family pedigree in Ohio with clinical signs of ADNIV were evaluated. Medical history, family history, and complete ocular examinations were obtained during regular clinic visits. Multimodal imaging including ocular coherence tomography, fluorescein angiography, wide-field fundus photographs, and Humphrey visual field testing was obtained for all five patients. Additionally, genetic testing for the Calpain-5 (CAPN5) gene was conducted on all patients. RESULTS: All five patients were noted to have a CAPN5 c.731T > C (p.L244P) mutation on genetic testing. Using multimodal imaging to supplement the clinical examination, pathologic changes such as retinal vascular inflammation, macular edema, and tractional retinal membranes were well illustrated and monitored over time. This allowed for earlier intervention when appropriate such as with intraocular steroid or systemic anti-inflammatory treatments. CONCLUSION: Phenotypic presentation varied among patients in this series, but is consistent with the spectrum of pathologic changes previously described in patients with other CAPN5 gene mutations. Monitoring of patients with ADNIV utilizing multimodal imaging can help better assess progression of this disease and guide treatment decisions. Additionally, increased genetic testing in patients with inherited retinal diseases may reveal novel gene mutations that could serve as potential targets for future genetic treatment regimens.

Improving Auditory Filter Estimation by Incorporating Absolute Threshold and a Level-dependent Internal Noise.

Auditory filter (AF) shape has traditionally been estimated with a combination of a notched-noise (NN) masking experiment and a power spectrum model (PSM) of masking. However, there are several challenges that remain in both the simultaneous and forward masking paradigms. We hypothesized that AF shape estimation would be improved if absolute threshold (AT) and a level-dependent internal noise were explicitly represented in the PSM. To document the interaction between NN threshold and AT in normal hearing (NH) listeners, a large set of NN thresholds was measured at four center frequencies (500, 1000, 2000, and 4000 Hz) with the emphasis on low-level maskers. The proposed PSM, consisting of the compressive gammachirp (cGC) filter and three nonfilter parameters, allowed AF estimation over a wide range of frequencies and levels with fewer coefficients and less error than previous models. The results also provided new insights into the nonfilter parameters. The detector signal-to-noise ratio (K) was found to be constant across signal frequencies, suggesting that no frequency dependence hypothesis is required in the postfiltering process. The ANSI standard "Hearing Level-0dB" function, i.e., AT of NH listeners, could be applied to the frequency distribution of the noise floor for the best AF estimation. The introduction of a level-dependent internal noise could mitigate the nonlinear effects that occur in the simultaneous NN masking paradigm. The new PSM improves the applicability of the model, particularly when the sound pressure level of the NN threshold is close to AT.

Comparative effectiveness of pharmacological interventions for hand osteoarthritis: a systematic review and network meta-analysis of randomised trials.

OBJECTIVE: To explore the comparative effectiveness of pharmacological interventions for hand osteoarthritis (OA). METHODS: We systematically searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception until 26 December 2021, for randomised trials of pharmacological interventions for people with hand OA. Two reviewers independently extracted study data and assessed the risk of bias. We calculated the effect sizes for pain (standardised mean differences) using Bayesian random effects models for network meta-analysis (NMA) and pairwise meta-analysis. Based on a pre-specified protocol, we prospectively registered the study at PROSPERO, CRD42021215393. RESULTS: We included 72 trials with 7609 participants. 65 trials (n=5957) were eligible for the quantitative synthesis, investigating 29 pharmacological interventions. Oral non-steroidal anti-inflammatory drugs (NSAIDs) and oral glucocorticoids' NMA effect sizes were -0.18 (95% credible interval -0.36 to 0.02) and -0.54 (-0.83 to -0.24), respectively, compared with placebo, and the result was consistent when limiting evidence to the pairwise meta-analysis of trials without high risk of bias. Intra-articular hyaluronate, intra-articular glucocorticoids, hydroxychloroquine, and topical NSAIDs' NMA effect sizes were 0.22 (-0.08 to 0.51), 0.25 (0.00 to 0.51), -0.01 (-0.19 to 0.18), and -0.14 (-0.33 to 0.08), respectively, compared with placebo. Oral NSAIDs were inferior to oral glucocorticoids with an NMA effect size of 0.36 (0.01 to 0.72). No intervention was superior to placebo when stratifying for thumb and finger OA. CONCLUSION: Oral NSAIDs and glucocorticoids are apparently effective pharmacological interventions in hand OA. Intra-articular therapies and topical NSAIDs were not superior to placebo.

Prognostic value of illness perception on changes in knee pain among elderly individuals: Two-year results from the Frederiksberg Cohort study.

Objective: To investigate the prognostic value of illness perception (IP) on knee pain, quality of life (QoL) and functional level in elderly individuals reporting knee pain. Design: A prospective cohort study of 1552 elderly with knee pain comparing two previously established clusters based on the Brief Illness Perception questionnaire. Cluster 1 ("Concerned optimists" [hypothesized unfavorable profile]; n â€‹= â€‹642) perceived their knee pain as a greater threat to them than Cluster 2 ("Unconcerned confident" [hypothesized favorable profile]; n â€‹= â€‹910). Primary outcome was the change from baseline to year 2 in the KOOS Pain subscale. Secondary outcomes were changes from baseline in quality of life (EuroQol-5 Domain and EQ VAS) and in the KOOS subscales Symptom, Activities of Daily Living, Knee-related QoL and Sports and recreation. Analyses were done on the original Intention-To-Survey (ITS) population, using repeated measures mixed linear models. Results: Among the ITS population, 841 (54%) responded to the 2-year survey. There was a statistically significant but clinically irrelevant cluster difference in the 2-year change from baseline in KOOS pain (mean difference: 6.0 KOOS points [95% CI: 7.3 to -4.7]) explained by a minor improvement in Cluster 1: (6.2 points) and no changes in Cluster 2: (0.2 points). Comparable results were found across the secondary outcomes. Clinically irrelevant cluster changes in IP were seen. Conclusion: In a cohort of people with knee pain, IP phenotype (i.e., Clusters) were of no prognostic value for the 2-year changes in pain, function, and QoL. Targeting IP may not be relevant in this patient population. Trial registration number and date of registration: The Frederiksberg Cohort study was pre-registered at clinicaltrials.gov (NCT03472300) on March 21, 2018.

Effect of gabapentin on ambulatory, direct, systemic arterial blood pressure in apparently healthy cats in the at-home and in-clinic environments.

OBJECTIVES: Situational increases in blood pressure (BP) frequently confound the accurate diagnosis of pathological systemic hypertension in cats. The objective of this study was to investigate the effect of gabapentin on direct, ambulatory systolic arterial BP (SBP) in cats in at-home and in-clinic environments. METHODS: Six adult purpose-bred cats with surgically implanted femoral artery telemetric BP-sensing catheters were administered 100 mg of gabapentin or a placebo orally in two randomized, masked, crossover study phases. In the first, direct BP was measured continuously in undisturbed cats for 24 h before (at-home baseline) and 4 h after administration of study drug. The mean SBP after administration of the drug was compared between treatments. In the second study period, cats were administered gabapentin or placebo 90 mins before transport to a clinic, where direct BP was measured continuously during a simulated veterinary visit that included an indirect BP measurement session. Changes in mean direct SBP relative to the 24-h at-home pre-treatment period were calculated for each of one waiting room and two examination-room periods, and compared between treatments. Concurrent in-clinic direct and indirect SBP measurements were compared within-cat. Data were compared using linear mixed models. RESULTS: Direct SBP data from one cat were excluded due to implant failure. There were no differences in at-home or in-clinic SBP between treatment groups, with large inter-individual variability. Cats in both treatment groups experienced in-clinic increases in direct SBP relative to at-home baseline (range 11-50 and 10-52 mmHg in placebo- and gabapentin-treated cats, respectively). Across all visits, direct SBP was 15.6 mmHg higher than indirect SBP (P <0.001). No effects of treatment on difference between direct and indirect SBP were identified. CONCLUSIONS AND RELEVANCE: Significant effects of gabapentin on direct SBP were not identified, though a type II error is possible. Situational increases cannot be excluded in gabapentin-treated cats with high SBP.