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We measured plasma human herpesvirus 8 (HHV8) DNA load in consecutive patients presenting with HIV-associated multicentric Castleman disease (MCD) and in contemporaneous patients who had Kaposi sarcoma (KS), lymphoma or other diagnoses. All 11 patients with MCD had detectable plasma HHV8 DNA compared with 18 (72%) of 25 patients with KS, none with lymphoma and one of 38 patients with other diagnoses. Detectable plasma HHV8 DNA levels were higher among MCD patients, median (interquartile range [IQR]) = 43,500 (5200-150,000) copies/mL, when compared with those with KS, median (IQR) = 320 (167-822) copies/mL and those with lymphoma and other diagnoses (one-way analysis of variance; P = 0.0303). Using receiver operating characteristic analysis, a cut-off of >1000 copies HHV8 DNA/mL of plasma helped to discriminate between MCD and other diagnoses, with a specificity of 94.7% and a negative predictive value of 97.3%. The level of HHV8 viraemia, while not diagnostic, may aid discrimination between patients with MCD and those with KS and other systemic illnesses. [ABSTRACT FROM AUTHOR]

BACKGROUND: Randomized control studies have not shown an association between treatment with tenofovir (TDF) and clinically significant kidney toxicity. However, multiple cases of renal tubular toxicity have been described in patients with HIV treated with TDF. It is unclear whether spot urine protein- or albumin-creatinine ratio is a sufficiently sensitive screening test to detect subclinical renal tubular toxicity in patients with HIV. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 99 patients with HIV with serum creatinine levels < 1.70 mg/dL and dipstick-negative proteinuria; 19 were antiretroviral treatment (ART) naive, 47 were on a TDF regimen, and 33 were on ART, but with no history of TDF exposure. PREDICTOR OR FACTOR: Exposure to TDF. OUTCOMES: Spot urine concentrations of retinol-binding protein (RBP; a low-molecular-weight protein normally reabsorbed by the proximal tubule), N-acetyl-beta-D-glucosaminidase (NAG; a proximal tubule lysosomal enzyme), albumin (A; a marker of glomerular disease), and protein (P; a standard clinical screening test for kidney pathological states) expressed as a ratio to creatinine (C; U(RBP/C), U(NAG/C), U(A/C), and U(P/C), respectively). RESULTS: There were no significant differences in median U(A/C) (ART-naive, 7.3 mg/g [range, 0-245.8 mg/g]; TDF, 9.0 mg/g [range, 0.1-184.1 mg/g]; and non-TDF, 10.5 mg/g [range, 2.6-261.6 mg/g]; P = 0.8). U(RBP/C) excretion was significantly higher in the TDF group (median, 214.2 microg/g [range, 26.8-17,454.5 microg/g]) than in the ART-naive group (92.5 microg/g [range, 21.3-3,969.0 microg/g]; P = 0.03); there was also a trend toward higher values than in the non-TDF group (111.6 microg/g [range, 31.0-6,136.3 microg/g]; P = 0.08). U(NAG/C) excretion was significantly higher in both the TDF (median, 394.7 micromol/h/g [range, 140.5-10,851.3 micromol/h/g]; P = 0.01) and non-TDF (406.8 micromol/h/g [range, 12.4-8,485.8 micromol/h/g]; P = 0.03) groups compared with the ART-naive group (218.6 micromol/h/g [range, 56.5-2,876.1 micromol/h/g]). U(P/C) was significantly higher in the TDF (median, 123.9 mg/g [range, 53.1-566.4 mg/g]) than the non-TDF group (97.3 mg/g [range, 0-451.3 mg/g]; P = 0.03). The proportion of patients with evidence of tubular dysfunction (increased U(RBP/C) and/or U(NAG/C)) was considerably higher than the proportion with an increase in U(A/C) or U(P/C) in all groups: for ART-naive, 52.6% vs 31.6% vs 25.0%; for TDF, 80.9% vs 29.8% vs 52.2%; and for non-TDF, 81.8% vs 39.4% vs 30.0%. The level of agreement among the different urinary test results was low. LIMITATIONS: Causality cannot be established from single measurements of urinary markers in a cross-sectional study. CONCLUSIONS: Patients with HIV had high rates of subclinical proteinuria, but neither U(P/C) nor U(A/C) is sufficiently sensitive alone to detect many of these cases. Patients using TDF have increased U(RBP/C) and U(P/C); the significance of this will need to be determined from longer-term outcome studies. [ABSTRACT FROM AUTHOR]

A reading program utilizing five components--a shortcut to phonemic awareness, Adapted Dolch words, Bridge lists and the Bridging process, reading comprehension, and American Sign Language development/language experience stories--was administered to 48 elementary school students at a residential school for the deaf. Data analyses reveal dramatic gains in students' reading levels and academic behavior, teachers' growth in reflective sign skills, and students' and teachers' overall growth in ASL skills, resulting in a more organized, consistent approach to linguistic input and usage. [ABSTRACT FROM AUTHOR]

National guidance on sexual health in England recommends service development to meet the specific needs of ethnic minority populations. Our aim was to evaluate mode of referral, number of sexually transmitted infections (STIs) diagnosed, and the offering and uptake of HIV testing in patients of South Asian ethnicity. A retrospective case-control study was undertaken in two London genito-urinary (GU) medicine clinics. There were 250 case-control pairs with approximately equal numbers of men and women. South Asians were less likely to have an STI (Odds ratio [OR] 0.66, 95% confidence interval [CI] 0.45, 0.97) or to report risk factors for HIV (OR 0.45, 95% CI 0.28, 0.71). Offering and uptake of HIV antibody testing were high in both South Asian and non-South Asian groups (OR 0.62, 95% CI 0.27, 1.51). South Asians were significantly more likely than controls to have been referred by other medical services rather than self-referred (OR 2.00, 95% CI 1.32, 3.01), which is in keeping with poorer access to GU medicine services in London. [ABSTRACT FROM AUTHOR]

Claviceptaceous endophytic fungi in the genus Epichloë mostly form a symbiotic relationship with cool-season grasses. Epichloë spp. are capable of producing bioactive alkaloids such as peramines, lolines, ergot alkaloids, and indole-diterpenes, which protect the host plant from herbivory by animals, insects, and nematodes. The host also benefits from enhanced tolerance to abiotic stresses, such as salt, drought, waterlogging, cold, heavy metals, and low nitrogen stress. The bioactive alkaloids produced can have both direct and indirect effects towards plant parasitic nematodes. Direct interaction with nematodes' motile stages can cause paralysis (nematostatic effect) or death (nematicidal effect). Indirectly, the metabolites may induce host immunity which inhibits feeding and subsequent nematode development. This review highlights the different mechanisms through which this interaction and the metabolites produced have been explored in the suppression of plant parasitic nematodes and also how the specific interactions between different grass genotypes and endophyte strains result in variable suppression of different nematode species. An understanding of the different grass-endophyte interactions and their successes and failures in suppressing various nematode species is essential to enable the proper selection of grass-endophyte combinations to identify the alkaloids produced, concentrations required, and determine which nematodes are sensitive to which specific alkaloids.

People living with HIV (PLWH) are at higher risk of reactivation of Chagas disease, a neglected tropical disease, caused by Trypanosoma cruzi . There are no data from UK HIV clinics on the prevalence of T. cruzi . We implemented T. cruzi screening at our clinic as part of routine care for PLWH with epidemiological risk factors. Among 86 patients screened, none had positive serology: one seropositive patient was identified due to increased clinician awareness. Implementing T. cruzi screening as part of routine clinical care was feasible, though labour intensive and identified at-risk individuals., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: The aim of this study was to retrospectively evaluate vision outcomes of dogs with primary angle closure glaucoma (PACG) that underwent Ahmed valve gonioimplantation (AVG) followed by lensectomy and endolaser cyclophotocoagulation (ECP) with or without bleb resection after AVG failure., Procedure: Medical records from 2008 to April 2022 were reviewed. All patients selected had an AVG performed first. Following valve failure, lensectomy-ECP was performed in addition to bleb resection as indicated. Additional ECP and AVG replacement surgeries were performed as deemed medically necessary. Main outcomes evaluated included vision preservation, average IOP reduction, and the number of glaucoma medications (both oral and topical) at 6, 12, 24, and 36 months., Results: Fourteen eyes from 13 patients were included in the study. Females were predominant (n = 9) compared with males (n = 4). Mean age at initial glaucoma diagnosis was 6.82 years. Following AVG and lensectomy-ECP, vision was preserved in 93%, 84%, 60%, and 48% of eyes at 1, 2, 3, and 4 years respectively. Following lensectomy-ECP, there was a significant reduction in mean IOP of 9.64 mmHg (p = .015) and 9.71 mmHg (p = .016) at 2 and 6 months, respectively. There was a reduction in mean IOP of 2.45, 7.25, and 12.25 mmHg at 12, 24, and 36 months, respectively, which was not statistically significant. There was a significant decrease in the number of glaucoma medications at all evaluated time points except 24 months., Conclusions: Combined AVG and lensectomy-ECP is successful in maintaining vision long term as well as decreasing IOP, and the number of glaucoma medications administered., (© 2023 The Authors. Veterinary Ophthalmology published by Wiley Periodicals LLC on behalf of American College of Veterinary Ophthalmologists.)

Blue copper proteins are models for illustrating how proteins tune metal properties. Nevertheless, the mechanisms by which the protein controls the metal site remain to be fully elucidated. A hindrance is that the closed shell Cu(I) site is inaccessible to most spectroscopic analyses. Carbon deuterium (C-D) bonds used as vibrational probes afford nonperturbative, selective characterization of the key cysteine and methionine copper ligands in both redox states. The structural integrity of Nostoc plastocyanin was perturbed by disrupting potential hydrogen bonds between loops of the cupredoxin fold via mutagenesis (S9A, N33A, N34A), variably raising the midpoint potential. The C-D vibrations show little change to suggest substantial alteration to the Cu(II) coordination in the oxidized state or in the Cu(I) interaction with the cysteine ligand. They rather indicate, along with visible and NMR spectroscopy, that the methionine ligand distinctly interacts more strongly with the Cu(I) ion, in line with the increases in midpoint potential. Here we show that the protein structure determines the redox properties by restricting the interaction between the methionine ligand and Cu(I) in the reduced state., (© 2023. Springer Nature Limited.)

It is considerably harder to generalize identity across different pictures of unfamiliar faces, compared with familiar faces. This finding hints strongly at qualitatively distinct processing of unfamiliar face stimuli-for which we have less expertise. Yet, the extent to which face selective versus generic visual processes drive outcomes during this task has yet to be determined. To explore the relative contributions of each, we contrasted performance on a version of the popular Telling Faces Together unfamiliar face matching task, implemented in both upright and inverted orientations. Furthermore, we included different age groups (132 British children ages 6 to 11 years [69.7% White], plus 37 British White adults) to investigate how participants' experience with faces as a category influences their selective utilization of specialized processes for unfamiliar faces. Results revealed that unfamiliar face matching is highly orientation-selective. Accuracy was higher for upright compared with inverted faces from 6 years of age, which is consistent with selective utilization of specialized processes for upright versus inverted unfamiliar faces during this task. The effect of stimulus orientation did not interact significantly with age, and there was no graded increase in the magnitude of inversion effects observed across childhood. Still, a numerically larger inversion effect in adults compared to children provides a degree of support for developmental changes in these specialized face abilities with increasing age/experience. Differences in the pattern of errors across age groups are also consistent with a qualitative shift in unfamiliar face processing that occurs some time after 11 years of age. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The culture media recommended for the isolation and enumeration of the Fusarium spp. lack selectivity for Fusarium graminearum . Five fungicides-Amistar ® (250 g·L -1 azoxystrobin), Filan ® (500 g·kg -1 boscalid), Comet ® 200 (200 g·L -1 pyraclostrobin), Imtrex ® (62.5 g·L -1 fluxapyroxad), Poraz ® (450 g·L -1 prochloraz)-were investigated for their potential as selective inhibitors in culture media for the isolation of F. graminearum from soil and plant material. Based on the screening, fluxapyroxad was further tested for selective inhibition for the isolation of F. graminearum from soil. Additionally, selective media were compared for the isolation of F. graminearum from plant material. The fungicides tested did not prove to be effective inhibitors for the development of selective media. For the detection of F. graminearum in plant material, Czapek Dox propiconazole dichloran agar was found to be a better medium than Komada's media, as the former resulted in colonies with darker pigmentation over a shorter incubation time and appeared to have a less inhibitory effect on F. graminearum growth.

Frequent occurrences of high levels of Fusarium mycotoxins have been recorded in Norwegian oat grain. To elucidate the influence of tillage operations on the development of Fusarium and mycotoxins in oat grain, we conducted tillage trials with continuous oats at two locations in southeast Norway. We have previously presented the content of Fusarium DNA detected in straw residues and air samples from these fields. Grain harvested from ploughed plots had lower levels of Fusarium langsethiae DNA and HT-2 and T-2 toxins (HT2 + T2) compared to grain from harrowed plots. Our results indicate that the risk of F. langsethiae and HT2 + T2 contamination of oats is reduced with increasing tillage intensity. No distinct influence of tillage on the DNA concentration of Fusarium graminearum and Fusarium avenaceum in the harvested grain was observed. In contrast to F. graminearum and F. avenaceum, only limited contents of F. langsethiae DNA were observed in straw residues and air samples. Still, considerable concentrations of F. langsethiae DNA and HT2 + T2 were recorded in oat grain harvested from these fields. We speculate that the life cycle of F. langsethiae differs from those of F. graminearum and F. avenaceum with regard to survival, inoculum production and dispersal.

Over recent decades, the Norwegian cereal industry has had major practical and financial challenges associated with the occurrence of Fusarium head blight (FHB) pathogens and their associated mycotoxins in cereal grains. Deoxynivalenol (DON) is one of the most common Fusarium -mycotoxins in Norwegian oats, however T-2 toxin (T2) and HT-2 toxin (HT2) are also commonly detected. The aim of our study was to rank Nordic spring oat varieties and breeding lines by content of the most commonly occurring Fusarium mycotoxins (DON and HT2 + T2) as well as by the DNA content of their respective producers. We analyzed the content of mycotoxins and DNA of seven fungal species belonging to the FHB disease complex in grains of Nordic oat varieties and breeding lines harvested from oat field trials located in the main cereal cultivating district in South-East Norway in the years 2011-2020. Oat grains harvested from varieties with a high FHB resistance contained on average half the levels of mycotoxins compared with the most susceptible varieties, which implies that choice of variety may indeed impact on mycotoxin risk. The ranking of oat varieties according to HT2 + T2 levels corresponded with the ranking according to the DNA levels of Fusarium langsethiae, but differed from the ranking according to DON and Fusarium graminearum DNA. Separate tests are therefore necessary to determine the resistance towards HT2 + T2 and DON producers in oats. This creates practical challenges for the screening of FHB resistance in oats as today's screening focuses on resistance to F. graminearum and DON. We identified oat varieties with generally low levels of both mycotoxins and FHB pathogens which should be preferred to mitigate mycotoxin risk in Norwegian oats.

Fusarium head blight (FHB) is an important disease of small grain cereals worldwide, resulting in reduced yield and quality as well as the contamination of harvested grains with mycotoxins. The key mycotoxin of concern is deoxynivalenol (DON), which has legislative and advisory limits in numerous countries. Cereal growers have a number of control options for FHB including rotation, cultivation, and varietal resistance; however, growers are still reliant on fungicides applied at flowering as part of an IPM program. Fungicides currently available to control FHB are largely restricted to triazole chemistry. This study conducted three field experiments to compare a new co-formulation of pydiflumetofen (a succinate dehydrogenase inhibitor (SDHI) with the tradename ADEPIDYN ™ ) and prothioconazole (a triazole) against current standard fungicides at various timings (flag leaf fully emerged, mid-head emergence, early flowering, and late flowering) for the control of FHB and DON. Overall, the co-formulation showed greater efficacy compared to either pydiflumetofen alone or current fungicide chemistry. This greater activity was demonstrated over a wide range of spray timings (flag leaf fully emerged to late flowering). The availability of an SDHI with good activity against FHB and the resulting DON contamination of harvested grain will give growers an additional tool within an IPM program that will provide a greater flexibility of spray application windows and reduce fungicide resistance selection pressure.

Fusarium graminearum is regarded as the main deoxynivalenol (DON) producer in Norwegian oats, and high levels of DON are occasionally recorded in oat grains. Weather conditions in the period around flowering are reported to have a high impact on the development of Fusarium head blight (FHB) and DON in cereal grains. Thus, it would be advantageous if the risk of DON contamination of oat grains could be predicted based on weather data. We conducted a functional data analysis of weather-based time series data linked to DON content in order to identify weather patterns associated with increased DON levels. Since flowering date was not recorded in our dataset, a mathematical model was developed to predict phenological growth stages in Norwegian spring oats. Through functional data analysis, weather patterns associated with DON content in the harvested grain were revealed mainly from about three weeks pre-flowering onwards. Oat fields with elevated DON levels generally had warmer weather around sowing, and lower temperatures and higher relative humidity or rain prior to flowering onwards, compared to fields with low DON levels. Our results are in line with results from similar studies presented for FHB epidemics in wheat. Functional data analysis was found to be a useful tool to reveal weather patterns of importance for DON development in oats.

Personal data is ubiquitous in the digital world, can be highly valuable in aggregate, and can lead to unintended intrusions for the data creator. However, individuals' expressions of concern about exposure of their personal information are generally not matched by their behavioural caution. One reason for this mismatch could be the varied and intangible value of personal data. We present three studies investigating the potential association between personal data value and privacy behaviour, assessing both individual and cross-cultural differences in personal data valuation, comparing collectivist and individualistic cultures. Study 1a, using a representative UK sample, found no relationship between personal data value and privacy behaviour. However, Study 1b found Indian (collectivist) participants' privacy behaviour was sensitive to personal data value, unlike US (individualist) participants. Study 2 showed that in a UK sample, privacy behaviour was sensitive to personal data value but only for individuals who think of themselves as more similar to others (i.e., self-construe as similar, rather than different). We suggest those who prioritise group memberships are more sensitive to unintentional disclosure harm and therefore behave in accordance with personal data valuations-which informs the privacy concern-behaviour relationship. Our findings can suggest approaches to encourage privacy behaviours., Competing Interests: The authors have declared that no competing interests exist.

Background: Surgical treatment of scaphoid nonunion has evolved over the years to include a variety of procedures and techniques involving a number of vascularized and nonvascularized bone grafting options and fixation strategies. Volar plating of scaphoid nonunions with use of pure cancellous nonvascularized autograft is a safe and effective treatment method with good functional outcomes and union rates 1 ., Description: Volar plating of the scaphoid nonunion is performed via a volar approach, with debridement and reduction of the nonunion site. A nonvascularized pure cancellous bone autograft is then harvested and impacted from the distal aspect of the ipsilateral radius or the olecranon. Finally, a low-profile volar locking plate is applied for fixation 2 ., Alternatives: There is no consensus regarding the optimal treatment of scaphoid nonunion. Headless compression screws are currently popular, and advances have been made over time to include various nonvascularized and vascularized corticocancellous grafts. The advent of plate fixation of the scaphoid has enabled the surgical treatment of nonunion to better replicate scaphoid morphology, allowing for improved biomechanical stability and optimizing the biologic milieu for healing., Rationale: Headless compression screws, although a reasonable option for most acute scaphoid fractures, may not be the most appropriate application for nonunions. Compression, in itself, is not required for the surgical treatment of scaphoid nonunion, and can even prove detrimental by forcing the reduction into a malunion. The stability of headless compression screws must rely on a structural graft to resist the compression and create friction. The more structural the graft, however, the less biologically active it tends to be. Further, the simple placement of a metallic screw within the fracture site is counter to orthopaedic principles because it dramatically lowers the surface area available for union. Volar locking plates address the shortcoming of headless compression screws by (1) directly buttressing the deforming forces superior to headless screws 3-6 ; (2) utilizing the most accessible, biologically active nonvascularized bone graft, which is pure cancellous graft; (3) allowing for maximal surface area contact for union; and (4) preserving the intraosseous vascular network within the scaphoid and its vascular supply at its dorsal ridge., Expected Outcomes: Volar scaphoid plating with cancellous bone grafting is a reliable technique with excellent union rates and favorable functional outcomes. A review of 34 patients with scaphoid nonunions with segmental defects treated with volar plates and pure cancellous autograft demonstrated 100% union as verified by computed tomography scans postoperatively 1 . Average Disabilities of the Arm, Shoulder and Hand scores and grip strengths improved by final follow-up. Another series of 13 scaphoid nonunions with osteonecrosis treated with volar plating and pure cancellous autograft showed 100% union and good patient-reported and functional outcomes, despite smokers, proximal poles, and previous failed surgical procedures in the cohort 2 . These favorable results are consistent with earlier reports of the modern plating systems; however, concerns for hardware-related complications have been elucidated over the years, including symptomatic hardware impingement 7 . This risk can be mitigated by proper surgical technique and plate placement., Important Tips: Clear visualization of the entire volar surface of the scaphoid is crucial. Take care not to reflect too much capsule, so as to cause ulnar translation of the carpus.Thorough debridement of nonviable bone is paramount. Using a 2.0 or 3.0-mm low-speed burr with continuous irrigation can be helpful. We have had successful unions even in cases in which the remaining proximal pole was just a cortical shell and essentially a hollow vessel for graft.Err on the side of verticalization of the scaphoid, overextending and supinating the distal pole. Overstuffing the nonunion site with cancellous autograft aids in reduction and maximizes the osteoinductive and osteoconductive properties of the graft.Impaction of the graft is crucial, and the surgeon should harvest more autograft than one might initially anticipate.Secure the plate to the proximal portion of the scaphoid first. There is less room for error on the proximal portion where plate positioning is more critical.Do not cross the scaphoid "line in the sand"; to do so will result in plate impingement on the radius. Proper placement of the plate is just distal to the point at which the convex surface of the proximal pole transitions to become the concave surface of the scaphoid waist, as viewed from a volar approach.Plate modification for proximal pole fractures and nonunions: removal of the most proximal hole in the plate allows for improved fixation despite the plate itself remaining behind the scaphoid "line in the sand." In these cases, the locking screws must be directed so that they buttress the subchondral bone of each pole, especially the proximal pole., Competing Interests: Disclosure: The authors indicated that no external funding was received for any aspect of this work. The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSEST/A337)., (Copyright © 2021 By The Journal Of Bone And Joint Surgery, Incorporated.)

When two people look at the same object in the environment and are aware of each other's attentional state, they find themselves in a shared-attention episode. This can occur through intentional or incidental signaling and, in either case, causes an exchange of information between the two parties about the environment and each other's mental states. In this article, we give an overview of what is known about the building blocks of shared attention (gaze perception and joint attention) and focus on bringing to bear new findings on the initiation of shared attention that complement knowledge about gaze following and incorporate new insights from research into the sense of agency. We also present a neurocognitive model, incorporating first-, second-, and third-order social cognitive processes (the shared-attention system, or SAS), building on previous models and approaches. The SAS model aims to encompass perceptual, cognitive, and affective processes that contribute to and follow on from the establishment of shared attention. These processes include fundamental components of social cognition such as reward, affective evaluation, agency, empathy, and theory of mind.

The transformation of quiescent keratocytes to activated fibroblasts and myofibroblasts (KFM transformation) largely depends on transforming growth factor beta (TGFβ) signaling. Initiation of the TGFβ signaling cascade results from binding of TGFβ to the labile type I TGFβ receptor (TGFβRI), which is stabilized by the 90 kDa heat shock protein (Hsp90). Since myofibroblast persistence within the corneal stroma can result in stromal haze and corneal fibrosis in patients undergoing keratorefractive therapy, modulation of TGFβ signaling through Hsp90 inhibition would represent a novel approach to prevent myofibroblast persistence. In vitro, rabbit corneal fibroblasts (RCFs) or stratified immortalized human corneal epithelial cells (hTCEpi) were treated with a Hsp90 inhibitor (17AAG) in the presence/absence of TGFβ1. RCFs were cultured either on tissue culture plastic, anisotropically patterned substrates, and hydrogels of varying stiffness. Cellular responses to both cytoactive and variable substrates were assessed by morphologic changes to the cells, and alterations in expression patterns of key keratocyte and myofibroblast proteins using PCR, Western blotting and immunocytochemistry. Transepithelial electrical resistance (TEER) measurements were performed to establish epithelial barrier integrity. In vivo, the corneas of New Zealand White rabbits were wounded by phototherapeutic keratectomy (PTK) and treated with 17AAG (3× or 6× daily) either immediately or 7 days after wounding for 28 days. Rabbits underwent clinical ophthalmic examinations, SPOTS scoring and advanced imaging on days 0, 1, 3, 7, 10, 14, 21 and 28. On day 28, rabbits were euthanized and histopathology/immunohistochemistry was performed. In vitro data demonstrated that 17AAG inhibited KFM transformation with the de-differentiation of spindle shaped myofibroblasts to dendritic keratocyte-like cells accompanied by significant upregulation of corneal crystallins and suppression of myofibroblast markers regardless of TGFβ1 treatment. RCFs cultured on soft hydrogels or patterned substrates exhibited elevated expression of α-smooth muscle actin (αSMA) in the presence of 17AAG. Treatment of hTCEpi cells disrupted zonula occludens 1 (ZO-1) adherens junction formation. In vivo, there were no differences detected in nearly all clinical parameters assessed between treatment groups. However, rabbits treated with 17AAG developed greater stromal haze formation compared with controls, irrespective of frequency of administration. Lastly, there was increased αSMA positive myofibroblasts in the stroma of 17AAG treated animals when compared with controls. Hsp90 inhibition promoted reversion of the myofibroblast to keratocyte phenotype, although this only occurred on rigid substrates. By contrast, in vivo Hsp90 inhibition was detrimental to corneal wound healing likely due to impairment in corneal epithelial closure and barrier function restoration. Collectively, our data demonstrated a strong interplay in vitro between biophysical cues and soluble signaling molecules in determining corneal stromal cell phenotype., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

To facilitate social interactions, humans need to process the responses that other people make to their actions, including eye movements that could establish joint attention. Here, we investigated the neurophysiological correlates of the processing of observed gaze responses following the participants' own eye movement. These observed gaze responses could either establish, or fail to establish, joint attention. We implemented a gaze leading paradigm in which participants made a saccade from an on-screen face to an object, followed by the on-screen face either making a congruent or incongruent gaze shift. An N170 event-related potential was elicited by the peripherally located gaze shift stimulus. Critically, the N170 was greater for joint attention than non-joint gaze both when task-irrelevant (Experiment 1) and task-relevant (Experiment 2). These data suggest for the first time that the neurocognitive system responsible for structural encoding of face stimuli is affected by the establishment of participant-initiated joint attention., (© The Author(s) 2020. Published by Oxford University Press.)

Background: The London patient (participant 36 in the IciStem cohort) underwent allogeneic stem-cell transplantation with cells that did not express CCR5 (CCR5Δ32/Δ32); remission was reported at 18 months after analytical treatment interruption (ATI). Here, we present longer term data for this patient (up to 30 months after ATI), including sampling from diverse HIV-1 reservoir sites., Methods: We used ultrasensitive viral load assays of plasma, semen, and cerebrospinal fluid (CSF) samples to detect HIV-1 RNA. In gut biopsy samples and lymph-node tissue, cell-copy number and total HIV-1 DNA levels were quantified in multiple replicates, using droplet digital PCR (ddPCR) and quantitative real-time PCR. We also analysed the presence of intact proviral DNA using multiplex ddPCR targeting the packaging signal (ψ) and envelope (env). We did intracellular cytokine staining to measure HIV-1-specific T-cell responses. We used low-sensitive and low-avidity antibody assays to measure the humoral response to HIV-1. We predicted the probability of rebound using a mathematical model and inference approach., Findings: HIV-1 viral load in plasma remained undetectable in the London patient up to 30 months (last tested on March 4, 2020), using an assay with a detection limit of 1 copy per mL. The patient's CD4 count was 430 cells per μL (23·5% of total T cells) at 28 months. A very low-level positive signal for HIV-1 DNA was recorded in peripheral CD4 memory cells at 28 months. The viral load in semen was undetectable in both plasma (lower limit of detection [LLD] <12 copies per mL) and cells (LLD 10 copies per 10 6 cells) at 21 months. CSF was within normal parameters at 25 months, with HIV-1 RNA below the detection limit (LLD 1 copy per mL). HIV-1 DNA by ddPCR was negative in rectum, caecum, and sigmoid colon and terminal ileum tissue samples at 22 months. Lymph-node tissue from axilla was positive for the long-terminal repeat (33 copies per 10 6 cells) and env (26·1 copies per 10 6 cells), negative for ψ and integrase, and negative by the intact proviral DNA assay, at 27 months. HIV-1-specific CD4 and CD8 T-cell responses have remained absent at 27 months. Low-avidity Env antibodies have continued to decline. Mathematical modelling suggests that the probability of remission for life (cure) is 98% in the context of 80% donor chimerism in total HIV target cells and greater than 99% probability of remission for life with 90% donor chimerism., Interpretation: The London patient has been in HIV-1 remission for 30 months with no detectable replication-competent virus in blood, CSF, intestinal tissue, or lymphoid tissue. Donor chimerism has been maintained at 99% in peripheral T cells. We propose that these findings represent HIV-1 cure., Funding: Wellcome Trust and amfAR (American Foundation for AIDS Research)., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)