Udder health outcomes in Irish herds participating in cellcheck dry cow consults.

The CellCheck Dry Cow Consult (DCC) was developed by the CellCheck Technical Working Group to enable farmers to engage with their nominated vet to develop farm-specific selective dry cow therapy (SDCT) plans, where appropriate. This study evaluated the effect of the DCC on farmer decision-making around dry cow therapy, and the udder health impact of implementing SDCT, in study herds over the 2019 and 2020 dry periods. The DCC was a 3-h consult, delivered and funded as part of the Targeted Advisory Service on Animal Health (TASAH). Herds that completed a DCC were invited to register for a Dry Cow Review the following year. The combined data set for analysis across both years comprised of 439 herds and 25,357 cows. Available herd size ranged from 25 to 800. The median SCC of cows dried off with teat sealant only was 47,000 cells/ml before drying off in 2019 and 48,000 cells/ml at first milk recording in 2020, and 43,000 cells/ml before drying off in 2020 and 39,000 cells/ml at first milking recording in 2021. Following both the 2019 and 2020 dry periods, cows tended to converge toward a similar median SCC early in the following lactation, irrespective of prior dry cow treatment strategy. The uptake of SDCT was greater in Review herds, with 21% of cows receiving teat sealant only in 2020, compared with 16.3% of cows in herds participating in a Consult for the first time in 2020. At an individual cow level, in both years dry period new infection rate (NIR) was approximately 2.7% higher for cows treated with teat sealant only, than for those treated with both dry cow antibiotic tubes and teat sealant, and 1.2% higher than cows treated with antibiotic only. Regardless of treatment, there was a significant association between increasing parity and the risk of a dry period new infection. Increasing herd size had a statistically significant effect on the risk of dry period new infection rates. At a herd level, there was no statistically significant increase in NIR when SDCT was used compared with herds where blanket dry cow therapy was used. While not without risk, SDCT can be successfully implemented in Irish herds; however, constant attention to hygiene and management is essential. Though there are challenges to face, facilitating continued farmer education and engagement with professional guidance will be important.

Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Concordance of diagnostic modalities in atypical skin and soft tissue infections in hospitalized patients.

Skin and soft tissue infections (SSTIs) have high rates of morbidity and mortality worldwide but lack reliable standards for diagnostic workup. As a result, atypical infections, more prevalent among immunocompromised patients, can be missed due to deviance from classic features only to be revealed later through inconsistently performed ancillary studies. Our objectives included to evaluate the sensitivities of clinical impression, histopathology, tissue culture, and molecular and non-molecular ancillary tests in diagnosing inpatient SSTIs, as well as to qualitatively discuss the unusual features making a subset of infections "atypical." To do so, we retrospectively reviewed the histopathologic reports and charts of inpatient dermatologic consults at a single tertiary care institution over a 3-year period. We identified a total of 111 cases of SSTIs evaluated by the inpatient dermatology consultation service with concurrent skin or soft tissue biopsy, with 32.4% representing atypical infections. Among these, clinical impression suggested infection in 9(25.0%), routine histopathology in 21(58.3%), specialized stains for microorganisms in 22(68.8%), and tissue culture in 15(68.2%). Due to incomplete picture that each modality by itself creates, we conclude that clinicians and pathologists should carry a low threshold for including SSTIs in their differential diagnoses and should evaluate with skin biopsy, special stains for microorganisms, and ancillary studies, particularly in critically ill individuals who necessitate timely diagnoses.

SARS-CoV-2 Variant Spike and accessory gene mutations alter pathogenesis.

The ongoing COVID-19 pandemic is a major public health crisis. Despite the development and deployment of vaccines against SARS-CoV-2, the pandemic persists. The continued spread of the virus is largely driven by the emergence of viral variants, which can evade the current vaccines through mutations in the Spike protein. Although these differences in Spike are important in terms of transmission and vaccine responses, these variants possess mutations in the other parts of their genome which may affect pathogenesis. Of particular interest to us are the mutations present in the accessory genes, which have been shown to contribute to pathogenesis in the host through innate immune signaling, among other effects on host machinery. To examine the effects of accessory protein mutations and other non-spike mutations on SARS-CoV-2 pathogenesis, we synthesized viruses where the WA1 Spike is replaced by each variant spike genes in a SARS-CoV-2/WA-1 infectious clone. We then characterized the in vitro and in vivo replication of these viruses and compared them to the full variant viruses. Our work has revealed that non-spike mutations in variants can contribute to replication of SARS-CoV-2 and pathogenesis in the host and can lead to attenuating phenotypes in circulating variants of concern. This work suggests that while Spike mutations may enhance receptor binding and entry into cells, mutations in accessory proteins may lead to less clinical disease, extended time toward knowing an infection exists in a person and thus increased time for transmission to occur. Significance: A hallmark of the COVID19 pandemic has been the emergence of SARS-CoV-2 variants that have increased transmission and immune evasion. Each variant has a set of mutations that can be tracked by sequencing but little is known about their affect on pathogenesis. In this work we first identify accessory genes that are responsible for pathogenesis in vivo as well as identify the role of variant spike genes on replication and disease in mice. Isolating the role of Spike mutations in variants identifies the non-Spike mutations as key drivers of disease for each variant leading to the hypothesis that viral fitness depends on balancing increased Spike binding and immuno-evasion with attenuating phenotypes in other genes in the SARS-CoV-2 genome.

Multifamily groups for patients with schizophrenia: an exploratory randomised controlled trial in Bosnia and Herzegovina.

BACKGROUND: Schizophrenia has a significant and lasting impact on the quality of life of patients and their families and is a leading cause of disability globally. Family interventions can be beneficial and may be particularly appropriate in settings with limited resources. We conducted an exploratory trial testing the effectiveness of a multifamily group intervention, which draws on the traditions of psychoeducation and trialogue, for improving the quality of life of patients with schizophrenia in Bosnia and Herzegovina. METHODS: We conducted an exploratory, randomised controlled trial with patients with schizophrenia attending an outpatient clinic in Sarajevo. Our primary outcome was improved quality of life at 6-month follow-up. Secondary outcomes included objective social outcomes, psychiatric symptoms and psychiatric hospitalisation measured at 6 and 12 months. Experiences of participants were assessed in post-intervention interviews. RESULTS: 72 patients were randomly assigned to either one of six multifamily groups or treatment as usual. Follow-up assessments were completed with 53 patients (74%) at 6 months and 55 patients (76%) at 12 months. The intervention significantly improved quality of life at 6 months (Cohen's d = 0.78, F = 6.37, p = 0.016) and 12 months (d = 1.08, F = 17.92, p < 0.001), compared with treatment as usual. Re-hospitalisation rates at 6 months and symptom levels also improved significantly whilst changes in other secondary outcomes failed to reach statistical significance. CONCLUSION: These findings suggest multifamily groups can be effective for improving the quality of life of patients with schizophrenia in Bosnia and Herzegovina. Further research is required to assess how multifamily groups may be scaled up in similar settings with limited resources.

The Emirates Mars Mission.

The Emirates Mars Mission (EMM) was launched to Mars in the summer of 2020, and is the first interplanetary spacecraft mission undertaken by the United Arab Emirates (UAE). The mission has multiple programmatic and scientific objectives, including the return of scientifically useful information about Mars. Three science instruments on the mission's Hope Probe will make global remote sensing measurements of the Martian atmosphere from a large low-inclination orbit that will advance our understanding of atmospheric variability on daily and seasonal timescales, as well as vertical atmospheric transport and escape. The mission was conceived and developed rapidly starting in 2014, and had aggressive schedule and cost constraints that drove the design and implementation of a new spacecraft bus. A team of Emirati and American engineers worked across two continents to complete a fully functional and tested spacecraft and bring it to the launchpad in the middle of a global pandemic. EMM is being operated from the UAE and the United States (U.S.), and will make its data freely available.

Community interventions for improving adult mental health: mapping local policy and practice in England.

BACKGROUND: Public mental health (PMH) aims to improve wellbeing and prevent poor mental health at the population level. It is a global challenge and a UK priority area for action. Communities play an important role in the provision of PMH interventions. However, the evidence base concerning community-based PMH interventions is limited, meaning it is challenging to compare service provision to need. Without this, the efficient and equitable provision of services is hindered. Here, we sought to map the current range of community-based interventions for improving mental health and wellbeing currently provided in England to inform priority areas for policy and service intervention. METHOD: We adopted an established mapping exercise methodology, comparing service provision with demographic and deprivation statistics. Five local authority areas of England were selected based on differing demographics, mental health needs and wider challenging circumstances (i.e. high deprivation). Community-based interventions were identified through: 1) desk-based research 2) established professional networks 3) chain-referral sampling of individuals involved in local mental health promotion and prevention and 4) peer researchers' insight. We included all community-based, non-clinical interventions aimed at adult residents operating between July 2019 and May 2020. RESULTS: 407 interventions were identified across the five areas addressing 16 risk/protective factors for PMH. Interventions for social isolation and loneliness were most prevalent, most commonly through social activities and/or befriending services. The most common subpopulations targeted were older adults and people from minority ethnic backgrounds. Interventions focusing on broader structural and environmental determinants were uncommon. There was some evidence of service provision being tailored to local need, though this was inconsistent, meaning some at-risk groups such as men or LGBTQ+ people from minority ethnic backgrounds were missed. Interventions were not consistently evaluated. CONCLUSIONS: There was evidence of partial responsiveness to national and local prioritising. Provision was geared mainly towards addressing social and individual determinants of PMH, suggesting more integration is needed to engage wider service providers and policy-makers in PMH strategy and delivery at the community level. The lack of comprehensive evaluation of services to improve PMH needs to be urgently addressed to determine the extent of their effectiveness in communities they serve.

A phase 1, single centre, open label, escalating dose study to assess the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) for HPV-associated head and neck cancer (HNC).

BACKGROUND: We conducted a phase 1 dose escalation study (ACTRN12618000140257 registered on 30/01/2018) to evaluate the safety, tolerability and immunogenicity of a therapeutic human papillomavirus (HPV) DNA vaccine (AMV002) in subjects previously treated for HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Eligible subjects had to have no evidence of recurrent and/or metastatic disease at least 12 weeks following the completion of treatment. Three dosing cohorts each consisted of four subjects: group 1: 0.25 mg/dose, group 2: 1 mg/dose, group 3: 4 mg/dose. AMV002 was delivered intradermally on days 0, 28 and 56. Incidence and severity of treatment-emergent adverse events (TEAE) including local reaction at the injection site, and vaccination compliance were recorded. T cell and antibody responses to HPV16 E6 and E7 were measured by interferon gamma (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) assay and enzyme-linked immunosorbent assay (ELISA). RESULTS: All subjects completed the vaccination programme and experienced mild discomfort at the injection site(s). Pre-immunisation, cell-mediated responses to HPV16 E6 and E7 were evident in all subjects, and E7-specific antibodies were detected in 11 (91.7%), reflecting previous exposure to HPV. Post-vaccination, 10 of 12 (83.3%) subjects responded to one or more of the E6 and/or E7 peptide pools, while 2 (16.7%) did not show additional vaccine-induced cell-mediated responses. Vaccination resulted in a ≥ 4-fold increase in anti-HPV16 E7 antibody titre in one subject in group 3. CONCLUSIONS: AMV002 was well tolerated at all dose levels and resulted in enhanced specific immunity to virus-derived tumour-associated antigens in subjects previously treated for HPV-associated OPSCC.

Using a Sweating Residuum/socket Interface Simulator for the Evaluation of Sweat Management Liners in Lower Limb Prosthetics.

BACKGROUND: Lab-based simulators can help to reduce variability in prosthetics research. However, they have not yet been used to investigate the effects of sweating at the residuum-liner interface. This work sought to create and validate a simulator to replicate the mechanics of residual limb perspiration. The developed apparatus was used to assess the effects of perspiration and different liner designs. METHODOLOGY: By scanning a cast, an artificial residuum was manufactured using a 3D-printed, transtibial bone model encased in silicone, moulded with pores. The pores allowed water to emit from the residuum surface, simulating sweating. Dry and sweating cyclic tests were performed by applying compressive and tensile loading, while measuring the displacement of the residuum relative to the socket. Tests were conducted using standard and perforated liners. FINDINGS: Although maximum displacement varied between test setups, its variance was low (coefficient of variation <1%) and consistent between dry tests. For unperforated liners, sweating increased the standard deviation of maximum displacement approximately threefold (0.04mm v 0.12mm, p<0.001). However, with the perforated liner, sweating had little effect on standard deviation compared to dry tests (0.04mm v 0.04mm, p=0.497). CONCLUSIONS: The test apparatus was effective at simulating the effect of perspiration at the residual limb. Moisture at the skin-liner interface can lead to inconsistent mechanics. Perforated liners help to remove sweat from the skin-liner interface, thereby mitigating these effects.

Genotyping-by-Sequencing for Analysis of the Genetic Variation of Podosphaera xanthii, Incitant of Cucurbit Powdery Mildew.

This research was conducted to identify species causing powdery mildew on cucurbits and to determine genetic variations among isolates of the pathogen. We collected 109 isolates from six cucurbit species hosts (Cucumis melo, Cucumis sativus, Cucurbita maxima, Cucurbita moschata, Cucurbita pepo, and Lagenaria siceraria) in California, Illinois, Indiana, Michigan, New York, Texas, Washington, and Wisconsin in the United States and in Italy. By sequencing the internal transcribed spacer region of the nuclear rDNA of these 109 isolates, Podosphaera xanthii was found as the only species causing powdery mildew on cucurbits in the United States. Genotyping-by-sequencing was applied to these 109 isolates to investigate their genetic diversity, which showed a trend of isolates clustering from New York and Italy. In addition, the virulence of 36 isolates was compared and a significant difference (P < 0.0001) was found among them. Furthermore, results of the virulence tests of 28 isolates from Illinois showed significant effects of collection years, hosts, and locations on the virulence of the isolates.

Using Perforated Liners to Combat the Detrimental Effects of Excessive Sweating in Lower Limb Prosthesis Users.

BACKGROUND: Excessive sweating of the residual limb has a substantial effect on the daily activities of people with lower limb amputation. Prosthetic liners offer protection and comfort to sensitive areas but often exacerbate perspiration. They act as insulators, trapping sweat on the skin's surface to the detriment of skin health. Recently, liners with perforations have been developed, allowing the moisture to escape. The goal of this study was to assess the impact of such liners. METHODS: A sample group of 13 patients with unilateral transtibial amputation, who wore a perforated liner (PL) as part of their current prescription, was compared to 20 control patients who wore non-perforated liners (NPL). During their routine appointments, they completed a survey of scientifically validated outcome measures relating to their limb health, pain and the impact on daily life over a 12-month period. RESULTS: Patients using the PL had healthier residual limbs, reporting higher scores on questions relating to limb health, experiencing fewer skin issues (p<0.001) and estimating a 61.8% lower rating in perceived sweat (p=0.004). Perhaps consequentially, there was a lower incidence of residual (p=0.012) and phantom (p=0.001) limb pain when compared to the control group. The prevalence of individual issues affecting the residual limbs of PL users was also lower. Of the issues that remained, only 23% were attributed to sweating in PL users, compared to 49% for the NPL group (p=0.066). PL users missed fewer days of work in the year (2.4 vs 11.6, p=0.267) and were also limited on fewer days (1.4 vs 75.4, p=0.009). CONCLUSION: The use of perforated liners shows much promise within prosthetic care, significantly improving the health of the residual limb. The observed effects on perceived sweat reduction, residual skin health, pain levels and patient limitation suggest that perforated liners are highly beneficial to patients.

Treatment gap and mental health service use among Syrian refugees in Sultanbeyli, Istanbul: a cross-sectional survey.

AIMS: Syrian refugees may have increased mental health needs due to the frequent exposure to potentially traumatic events and violence experienced during the flight from their home country, breakdown of supportive social networks and daily life stressors related to refugee life. The aim of this study is to report evidence on mental health needs and access to mental health and psychosocial support (MHPSS) among Syrians refugees living in Sultanbeyli-Istanbul, Turkey. METHODS: A cross-sectional survey was conducted among Syrian refugees aged 18 years or over in Sultanbeyli between February and May 2018. We used random sampling to select respondents by using the registration system of the municipality. Data among 1678 Syrian refugees were collected on mental health outcomes using the Posttraumatic Stress Disorder (PTSD) Checklist (PCL-5) and the Hopkins Symptoms Checklist (HSCL-25) for depression and anxiety. We also collected data on health care utilisation, barriers to seeking and continuing care as well as knowledge and attitudes towards mental health. Descriptive analyses were used. RESULTS: The estimated prevalence of symptoms of PTSD, depression and anxiety was 19.6, 34.7 and 36.1%, respectively. In total, 249 respondents (15%) screened positive for either PTSD, depression or anxiety in our survey and self-reported emotional/behavioural problems since arriving in Sultanbeyli. The treatment gap (the proportion of these 249 people who did not seek care) was 89% for PTSD, 90% for anxiety and 88% for depression. Several structural and attitudinal barriers for not seeking care were reported, including the cost of mental health care, the belief that time would improve symptoms, fear of being stigmatised and lack of knowledge on where and how to get help. Some negative attitudes towards people with mental health problems were reported by respondents. CONCLUSIONS: Syrian refugees hardly access MHPSS services despite high mental health needs, and despite formally having access to the public mental health system in Turkey. To overcome the treatment gap, MHPSS programmes need to be implemented in the community and need to overcome the barriers to seeking care which were identified in this study. Mental health awareness raising activities should be provided in the community alongside the delivery of psychological interventions. This is to increase help-seeking and to tackle negative attitudes towards mental health and people with mental health problems.

Quality of reporting and fragility index for randomized controlled trials in the vesicoureteral reflux literature: where do we stand?

BACKGROUND/INTRODUCTION: Randomized controlled trials (RCTs) are considered the "gold standard" methodology for examining the effects of clinical interventions, yet only 1% of urology literature employs this design. The Consolidated Standards of Reporting Trials (CONSORT) statement contains a standardized checklist of 37 items to be included when reporting RCTs to ensure transparency and completeness of information [2]. Despite the robust design of RCTs, the number of events can greatly change the significance of the results, which can be represented by the fragility index (FI). OBJECTIVE: The objective was to assess the quality of reporting of RCTs in the pediatric vesicoureteral reflux (VUR) literature using the 2010 CONSORT statement and, for studies with significant positive findings, to determine the FI as a measure of robustness of the results. STUDY DESIGN: A comprehensive search was conducted through MEDLINE® and Embase® to identify RCTs in VUR literature from 2000 to 2016. Two reviewers independently selected articles, which were evaluated using the CONSORT checklist. An overall quality of reporting score (OQS) (%) was calculated by dividing the number of checklist items present in each study by the maximum possible score (34) and expressed as a percentage. Studies were classified as low (<40%), moderate (40-70%) and high quality (>70%) based on the modified assessing the methodological quality of systematic reviews (AMSTAR) checklist. Of the 2052 initial matches, 98% were excluded due to methodology or content, a further 28 studies were found not to meet inclusion criteria after full text review. The FI was calculated for the 7 studies that met inclusion criteria with significantly different results by manually adding events to the study groups until p>0.05. RESULTS: Twenty-two studies met inclusion criteria. The mean OQS was 46+17% with 9 (41%) identified as low quality (score <40%), 11 (50%) as moderate (40-70%) and 2 (9%) as high quality (>70%). There was no significant difference in OQS between RCTs with a sample size > 100 (n=15) versus <100 patients (n=7) (45+17% vs. 47+17%, p=0.7). However, we noted a difference when we compared RCTs with biostatistician support (n=4) vs. those without (n=18) (59+20% vs. 43+15%, p<0.05). Seven studies reported significant positive results making calculation of FI possible. The mean FI was 5.8+5.1 indicating that most studies were fragile. There was no correlation between the OQS and FI. DISCUSSION AND CONCLUSION: The mean OQS of VUR RCTs was suboptimal (46%), with most studies having low FI scores indicating the instability of the findings. The only variable that significantly impacted the OQS was biostatistician support. Implementation of the CONSORT checklist with a minimum of 50% inclusion as a prerequisite for submission of manuscripts may improve the quality and transparency of reporting. Calculation of the FI could provide readers with an objective measure of robustness for the published trials, allowing for appropriate interpretation of the results.

The Influence of Hydraulic Ankles and Microprocessor-control on the Biomechanics of Trans-tibial Amputees During Quiet Standing on a 5° Slope.

BACKGROUND: Lower limb amputees have a high incidence of comorbidities, such as osteoarthritis, which are believed to be caused by kinetic asymmetries. A lack of prosthetic adaptation to different terrains requires kinematic compensations, which may influence these asymmetries. METHOD: Six SIGAM grade E-F trans-tibial amputees (one bilateral) wore motion capture markers while standing on force plates, facing down a 5° slope. The participants were tested under three prosthetic conditions; a fixed attachment foot (FIX), a hydraulic ankle (HYD) and a microprocessor foot with a 'standing support' mode (MPF). The resultant ground reaction force (GRF) and support moment for prosthetic and sound limbs were chosen as outcome measures. These were compared between prosthetic conditions and to previously captured able-bodied control data. RESULTS: The distribution of GRF between sound and prosthetic limbs was not significantly affected by foot type. However, the MPF condition required fewer kinematic compensations, leading to a reduction in sound side support moment of 59% (p=0.001) and prosthetic side support moment of 43% (p=0.02) compared to FIX. For the bilateral participant, only the MPF positioned the GRF vector anterior to the knees, reducing the demand on the residual joints to maintain posture. CONCLUSIONS: For trans-tibial amputees, loading on lower limb joints is affected by prosthetic foot technology, due to the kinematic compensations required for slope adaptation. MPFs with 'standing support' might be considered reasonable and necessary for bilateral amputees, or amputees with stability problems due to the reduced biomechanical compensations evident.

The Influence of Perforated Prosthetic Liners on Residual Limb Wound Healing: a Case Report.

CASE DESCRIPTION: Good residual limb skin health is vital to successful prosthetic prescription. Unnatural loading profiles and excessive sweating can lead to skin and soft tissue problems. Perforated liners allow the transport of moisture away from the skin and allow negative pressure (a condition that has been shown to aid wound healing) to act directly on the residuum surface. AIM: Assess the effects of perforated prosthetic liner use, particularly with respect to wound healing. METHOD: Three patient histories were retrospectively reviewed following prescription of perforated prosthetic liners due to excessive sweating or prolonged residual limb health concerns. Photographic records from patient files were used to document changes in residual limb condition. Patients also provided subjective feedback regarding their experiences. FINDINGS: Two cases described active amputees with persistent blistering irritated during exercise. Another case described a patient of low mobility level with a history of residual limb skin infections. All saw their conditions heal and reported a reduction in problematic sweating. Two patients reported cancelling surgical interventions after substantial improvements with the perforated liner. DISCUSSION: These findings provide evidence that the use of perforated prosthetic liners allow improvements in residual limb health, while still permitting prosthetic use.

Predicting the risk of cucurbit downy mildew in the eastern United States using an integrated aerobiological model.

Cucurbit downy mildew caused by the obligate oomycete, Pseudoperonospora cubensis, is considered one of the most economically important diseases of cucurbits worldwide. In the continental United States, the pathogen overwinters in southern Florida and along the coast of the Gulf of Mexico. Outbreaks of the disease in northern states occur annually via long-distance aerial transport of sporangia from infected source fields. An integrated aerobiological modeling system has been developed to predict the risk of disease occurrence and to facilitate timely use of fungicides for disease management. The forecasting system, which combines information on known inoculum sources, long-distance atmospheric spore transport and spore deposition modules, was tested to determine its accuracy in predicting risk of disease outbreak. Rainwater samples at disease monitoring sites in Alabama, Georgia, Louisiana, New York, North Carolina, Ohio, Pennsylvania and South Carolina were collected weekly from planting to the first appearance of symptoms at the field sites during the 2013, 2014, and 2015 growing seasons. A conventional PCR assay with primers specific to P. cubensis was used to detect the presence of sporangia in rain water samples. Disease forecasts were monitored and recorded for each site after each rain event until initial disease symptoms appeared. The pathogen was detected in 38 of the 187 rainwater samples collected during the study period. The forecasting system correctly predicted the risk of disease outbreak based on the presence of sporangia or appearance of initial disease symptoms with an overall accuracy rate of 66 and 75%, respectively. In addition, the probability that the forecasting system correctly classified the presence or absence of disease was ≥ 73%. The true skill statistic calculated based on the appearance of disease symptoms in cucurbit field plantings ranged from 0.42 to 0.58, indicating that the disease forecasting system had an acceptable to good performance in predicting the risk of cucurbit downy mildew outbreak in the eastern United States.

Predicted coreceptor usage at end-stage HIV disease in tissues derived from subjects on antiretroviral therapy with an undetectable plasma viral load.

HIV cure research is increasingly focused on anatomical tissues as sites for residual HIV replication during combined antiretroviral therapy (cART). Tissue-based HIV could contribute to low-level immune activation and viral rebound over the course of infection and could also influence the development of diseases, such as atherosclerosis, neurological disorders and cancers. cART-treated subjects have a decreased and irregular presence of HIV among tissues, which has resulted in a paucity of actual evidence concerning how or if HIV persists, replicates and evolves in various anatomical sites during therapy. In this study, we pooled 1806 HIV envelope V3 loop sequences from twenty-six tissue types (seventy-one total tissues) of six pre-cART subjects, four subjects with an unknown cART history who died with profound AIDS, and five subjects who died while on cART with an undetectable plasma viral load. A computational approach was used to assess sequences for their ability to utilize specific cellular coreceptors (R5, R5 and X4, or X4). We found that autopsied tissues obtained from virally suppressed cART+ subjects harbored both integrated and expressed viruses with similar coreceptor usage profiles to subjects with no or ineffective cART therapy (i.e., significant plasma viral load at death). The study suggests that tissue microenvironments provide a sanctuary for the continued evolution of HIV despite cART.

Novel Application of Localized Nanodelivery of Anti-Interleukin-6 Protects Organ Transplant From Ischemia-Reperfusion Injuries.

Ischemia-reperfusion injury (IRI) evokes intragraft inflammatory responses, which markedly augment alloimmune responses against the graft. Understanding the mechanisms underlying these responses is fundamental to develop therapeutic regimens to prevent/ameliorate organ IRI. Here, we demonstrate that IRI results in a marked increase in mitochondrial damage and autophagy in dendritic cells (DCs). While autophagy is a survival mechanism for ischemic DCs, it also augments their production of interleukin (IL)-6. Allograft-derived dendritic cells (ADDCs) lacking autophagy-related gene 5 (Atg5) showed higher death rates posttransplantation. Transplanted ischemic hearts from CD11cCre/Atg5 conditional knockout mice showed marked reduction in intragraft expression of IL-6 compared with controls. To antagonize the effect of IL-6 locally in the heart, we synthesized novel anti-IL-6 nanoparticles with capacity for controlled release of anti-IL-6 over time. Compared with systemic delivery of anti-IL-6, localized delivery of anti-IL-6 significantly reduced chronic rejection with a markedly lower amount administered. Despite improved allograft histology, there were no changes to splenic T cell populations, illustrating the importance of local IL-6 in driving chronic rejection after IRI. These data carry potential clinical significance by identifying an innovative, targeted strategy to manipulate organs before transplantation to diminish inflammation, leading to improved long-term outcomes.