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Objective: The present study examined (a) the presence of early maladaptive schemas and coping responses in children who have experienced maltreatment, (b) the relationship between early maladaptive schemas and coping responses, and (c) how qualitative findings compare to previous theoretical structures in quantitative studies., Method: There were 100 participants ( M age = 10.72 years, SD = 3.35; 64 girls, 30 boys, six transgender/nonbinary), with 70% identifying as White. Data were collected in collaboration with a community child advocacy center through forensic interviews in cases of reported child abuse. Early maladaptive schemas were assessed using an adapted version of the Dusseldorf Illustrated Schema Questionnaire for Children. Coping responses were assessed using the COPE Inventory. Information about individual and abuse factors was gathered from case reports. Child advocacy center staff completed the measures based on information obtained during forensic interviews., Results: All assessed early maladaptive schemas were endorsed in this sample; children reported an ability to adapt through the use of socially supported and self-sufficient coping responses. Hierarchical cluster analysis examining word similarity within coded texts demonstrated that subjugation and self-sacrifice were most strongly related., Conclusion: This mixed-method study integrating children's voices contributes a new perspective on early maladaptive schemas and coping responses that can provide education to multidisciplinary teams involved in forensic interviews. However, limits to generalizability must be considered given that the sample was derived from one region in the U.S. Midwest. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Francisella tularensis is a Gram-negative facultative intracellular bacterial pathogen that is classified by the Centers for Disease Control and Prevention as a Tier 1 Select Agent. F. tularensis infection causes the disease tularemia, also known as rabbit fever. Treatment of tularemia is limited to few effective antibiotics which are associated with high relapse rates, toxicity, and potential emergence of antibiotic-resistant strains. Consequently, new therapeutic options for tularemia are needed. Through screening a focused chemical library and subsequent structure-activity relationship studies, we have discovered a new and potent inhibitor of intracellular growth of Francisella tularensis , D8-03. Importantly, D8-03 effectively reduces bacterial burden in mice infected with F. tularensis . Preliminary mechanistic investigations suggest that D8-03 works through a potentially novel host-dependent mechanism and serves as a promising lead compound for further development.

Introduction: Medication errors during hospital discharge can lead to adverse outcomes, medication-related readmissions, and increased health care costs. Pharmacist-led medication reconciliation at discharge is a potential solution to mitigate poor outcomes and optimize medication safety., Objectives: This study aimed to quantify medication errors identified at discharge and characterize the severity of patient harm prevented following pharmacist-led discharge medication reconciliation. Cost avoidance analysis was conducted to determine its associated financial impact., Methods: Patients discharged from an adult internal medicine service during October 2022, were included in this one-month pilot prospective quality improvement study. Number of errors at discharge were documented, categorized by type, and adjudicated for severity of potential harm. Error severity was classified based on a modified National Coordinating Council for Medication Error Reporting and Prevention Medication Error Index. Cost avoidance was calculated based on whether each error would have resulted in additional medical encounters and length of stay., Results: Thirty-one patients were included in the analysis. Forty errors were identified by pharmacist-led medication reconciliation at discharge, with a mean of 1.3±1.9 errors per patient and 68% of patients having at least one error. The most common errors were duplication of therapy (25%) and medication access barriers at discharge (25%). The severity of errors included low (22.5%), serious (75%), and life-threatening harm (2.5%). Thirty-five percent of errors could have led to emergency visits or hospital readmissions. The estimated total cost for errors was $25,600. Pharmacist labor cost for reconciliation was $816. Cost avoidance was $24,784 from the 14 errors at discharge that could have resulted in additional emergency or inpatient visits., Conclusion: Pharmacist-led medication reconciliation at discharge may prevent harm from reaching patients, decrease cost from unnecessary health encounters, and stop the error from continuing across transitions of care., Competing Interests: Conflict of interest statement The authors declare no conflicts of interest.

Autistic adults participate less and express lower satisfaction in leisure activities than nonautistic adults, although literature is limited. The multifaceted nature of leisure participation makes it challenging to measure, with most measures being retrospective. Ecological momentary assessments (EMA) can reduce recall bias. This pilot study assessed the feasibility and acceptability of EMA among autistic adults. Participants (N = 40) were recruited via email and online. After completing a baseline interview, participants were asked to complete a once-daily survey for 30 days, in which they received survey links through a text messaging smartphone app. Surveys asked participants to report whether they participated in any leisure activities during the day, their level of enjoyment, with whom they interacted, and where they participated. The EMA appeared feasible in this sample, as participants completed the daily survey on average 27.05 (SD = 3.92) days. Regarding acceptability, most agreed that survey timing was convenient, that it was easy to enter responses and answer questions daily, and that they had enough response time. Overall, this study supports the use of EMA methodology among autistic adults. Future research should follow and improve upon these EMA data collection practices to examine daily behavior and well-being among autistic adults., (©AAIDD.)

Background: The Commission on Cancer implemented Standard 5.8 in 2021, which requires removal of 3 mediastinal nodes and 1 hilar node with lung cancer resection. We conducted a national survey to assess whether surgeons who treat lung cancer in different clinical settings correctly identify mediastinal lymph node stations., Methods: Cardiac or thoracic surgeons expressing interest in lung cancer surgery on the Cardiothoracic Surgery Network were asked to complete a 7-question survey assessing their knowledge of lymph node anatomy. General surgeons whose practice includes thoracic surgery were invited through American College of Surgeon's Cancer Research Program. Results were analyzed using Pearson's chi-square test. Multivariable linear regression was used to identify predictors of a higher score on the survey., Results: Of the 280 surgeons that responded, 86.8% were male and 13.2% were female; the median age was 50 years. Of these surgeons, 211 (75.4%) were thoracic, 59 (21.1%) were cardiac, and 10 (3.6%) were general surgeons. Surgeons were most likely to correctly identify lymph node stations 8R and 9R and least likely to correctly identify the midline pretracheal node just superior to the carina (4R). Surgeons whose practice involved a greater percentage of thoracic surgery patients and surgeons who performed a greater number of lobectomies scored higher on the lymph node assessment., Conclusion: Knowledge of mediastinal node anatomy among surgeons who perform thoracic surgery is generally high, but varies by clinical setting. Efforts are under way to better educate lung cancer surgeons on nodal anatomy, and to increase adoption of Standard 5.8., Competing Interests: Disclosure None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objectives: Multiple reforms aimed at improving the Chinese population's health have been introduced in recent years, including several designed to improve access to innovative drugs. We sought to review current factors affecting access to innovative drugs in China and to anticipate future trends., Methods: Targeted reviews of published literature and statistics on the Chinese healthcare system, medical insurance and reimbursement processes were conducted, as well as interviews with five Chinese experts involved in the reimbursement of innovative drugs., Results: Drug reimbursement in China is becoming increasingly centralized due to the removal of provincial pathways, the establishment of the National Healthcare Security Administration and the implementation of the National Reimbursement Drug List (NRDL), which is now the main route for drug reimbursement in China. There is also an increasing number of other channels via which patients may access innovative treatments, including various types of commercial insurance and special access. Health technology assessment (HTA) and health economic evidence are becoming pivotal elements of the NRDL decision-making process. Alongside the optimization of HTA decision making, innovative risk-sharing agreements are anticipated to be increasingly leveraged in the future to optimize access to highly specialized technologies and encourage innovation while safeguarding limited healthcare funds., Conclusions: Drug public reimbursement in China continues to align more closely with approaches widely used in Europe in terms of HTA, health economics and pricing. Centralization of decision-making processes for public reimbursement of innovative drugs allows consistency in assessment and access, which optimizes the improvement of the Chinese population's health., Competing Interests: Bérengère Macabeo, Linda Zheng, and Philippe Laramée were employees of Pierre Fabre Group at the time of the conduction of this study. Liam Wilson and Petar Atanasov were employees of Amaris Consulting Ltd., a paid consultant to Pierre Fabre Group to support the conduction of this study., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Objective: Childhood emotional abuse has been linked with mental and physical health concerns yet may be perceived as less severe than other forms of childhood abuse. The present study aims to (a) understand perceptions of childhood abuse forms across psychologists, general college-level students, and the general public and (b) investigate whether personal emotional abuse history affects perceptions of emotional abuse., Method: Participants ( N = 444) completed the Childhood Trauma Questionnaire-Short Form and provided perceived abuse severity and offender responsibility on eight case vignettes of emotional, physical, sexual, and no abuse. Research Question 1 was tested with a two-way (Vignette Type × Participant Type) multivariate analysis of variance performed on perceived severity and offender responsibility scores. Research Question 2 included abuse history as a third factor to examine potential moderation., Results: All three groups perceived scenarios regarding emotional abuse as less severe and the offender less responsible than scenarios regarding sexual or physical abuse. Unexpectedly, psychologists were just as variable in their perceptions of abuse severity across abuse forms, as compared to the general public and college students. However, psychologists with emotional abuse histories provided more severe ratings on emotional abuse items, more in line with general public perceptions. College students' and the general public's relative ratings were roughly equivalent regardless of emotional abuse history., Conclusions: The study calls for more attention to emotional abuse in psychologist training programs. Research and training to increase understanding of emotional abuse and its sequelae could move forward related educational outreach and legal proceedings. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

We have previously identified mitogen-activated protein kinase-activated protein kinase 2 (MK2) is required for caspase-3 nuclear translocation in the execution of apoptosis; however, little is known of the underlying mechanisms. Therefore, we sought to determine the role of kinase and nonkinase functions of MK2 in promoting nuclear translocation of caspase-3. We identified two non-small cell lung cancer cell lines for use in these experiments based on low MK2 expression. Wild-type, enzymatic and cellular localization mutant MK2 constructs were expressed using adenoviral infection. Cell death was evaluated by flow cytometry. In addition, cell lysates were harvested for protein analyses. Phosphorylation of caspase-3 was determined using two-dimensional gel electrophoresis followed by immunoblotting and in vitro kinase assay. Association between MK2 and caspase-3 was evaluated using proximity-based biotin ligation assays and co-immunoprecipitation. Overexpression of MK2 resulted in nuclear translocation of caspase-3 and caspase-3-mediated apoptosis. MK2 directly phosphorylates caspase-3; however, phosphorylation status of caspase-3 or MK2-dependent phosphorylation of caspase-3 did not alter caspase-3 activity. The enzymatic function of MK2 was dispensable in nuclear translocation of caspase-3. MK2 and caspase-3 associated together and a nonenzymatic function of MK2, chaperoned nuclear trafficking, is required for caspase-3-mediated apoptosis. Taken together, our results demonstrate a nonenzymatic role for MK2 in the nuclear translocation of caspase-3. Furthermore, MK2 may function as a molecular switch in regulating the transition between the cytosolic and nuclear functions of caspase-3.

Non-small cell lung cancers (NSCLCs) demonstrate intrinsic resistance to cell death, even after chemotherapy. Previous work suggested defective nuclear translocation of active caspase-3 in observed resistance to cell death. We have identified mitogen-activated protein kinase-activated protein kinase 2 (MK2; encoded by the gene MAPKAPK2 ) is required for caspase-3 nuclear translocation in the execution of apoptosis in endothelial cells. The objective was to determine MK2 expression in NSCLCs and the association between MK2 and clinical outcomes in patients with NSCLC. Clinical and MK2 mRNA data were extracted from two demographically distinct NSCLC clinical cohorts, North American (The Cancer Genome Atlas, TCGA) and East Asian (EA). Tumor responses following first round of chemotherapy were dichotomized as clinical response (complete response, partial response, and stable disease) or progression of disease. Multivariable survival analyses were performed using Cox proportional hazard ratios and Kaplan-Meier curves. NSCLC exhibited lower MK2 expression than SCLC cell lines. In patients, lower tumor MK2 transcript levels were observed in those presenting with late-stage NSCLC. Higher MK2 expression was associated with clinical response following initial chemotherapy and independently associated with improved 2-yr survival in two distinct cohorts, 0.52 (0.28-0.98) and 0.1 (0.01-0.81), TCGA and EA, respectively, even after adjusting for common oncogenic driver mutations. Survival benefit of higher MK2 expression was unique to lung adenocarcinoma when comparing across various cancers. This study implicates MK2 in apoptosis resistance in NSCLC and suggests prognostic value of MK2 transcript levels in patients with lung adenocarcinoma.

Shiraz disease (SD) is an economically important virus-associated disease that can significantly reduce yield in sensitive grapevine varieties and has so far only been reported in South Africa and Australia. In this study, RT-PCR and metagenomic high-throughput sequencing was used to study the virome of symptomatic and asymptomatic grapevines within vineyards affected by SD and located in South Australia. Results showed that grapevine virus A (GVA) phylogroup II variants were strongly associated with SD symptoms in Shiraz grapevines that also had mixed infections of viruses including combinations of grapevine leafroll-associated virus 3 (GLRaV-3) and grapevine leafroll-associated virus 4 strains 5, 6 and 9 (GLRaV-4/5, GLRaV-4/6, GLRaV-4/9). GVA phylogroup III variants, on the other hand, were present in both symptomatic and asymptomatic grapevines, suggesting no or decreased virulence of these strains. Similarly, only GVA phylogroup I variants were found in heritage Shiraz grapevines affected by mild leafroll disease, along with GLRaV-1, suggesting this phylogroup may not be associated with SD.

The purpose of this article is to review the objectives of the American College of Surgeons Commission on Cancer Operative Standards with a specific focus on Standard 5.5, which pertains to curative intent wide local excision of primary cutaneous melanoma lesions. We review the details and rationale of the standard itself, including its requirement to include specific elements and responses in synoptic format in operative reports., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The aim of this study is to report two cases of paediatric Yolk sac tumours (YST) of the orbit and sinonasal tract, with a major review on the subject., Methods: Two case reports along with a comprehensive retrospective literature review of all English language publications between 1974 and 2021 is presented. Literature review examined the demographics, clinical presentation and diagnostic and prognostic factors of extragonadal YSTs of the orbit and sinonasal tract., Results: Orbit and sinuses are rare sites for YST, with only 25 paediatric cases reported in the literature. Extragonadal yolk sac tumours carry a significantly worse outcome than those localised to the gonads, with the 5-year survival of 66% and 81-89%, respectively. Our review found the median age of presentation to be 18 months (18 months for males and 24 months for females), and females are more commonly affected. The most common presentations were proptosis, facial swelling and ophthalmoplegia. Treatments and therefore outcomes varied in the cases due to the large time period. Of the cases reported in the last 10 years, all patients with data provided were alive and disease-free at follow-up., Conclusion: Sino-orbital yolk sac tumours are rare and have variable presentations, dependent on the extent of local invasion. Early diagnosis and treatment with multimodal therapy are paramount in having improved overall survival.

Background: A 2019 public workshop convened by the National Academies of Sciences, Engineering and Medicine (NASEM) Roundtable on Health Literacy identified a need to develop evidence-based guidance for best practices for health literacy and patient activation in clinical trials., Purpose: To identify studies of health literacy interventions within medical care or clinical trial settings that were associated with improved measures of health literacy or patient activation, to help inform best practices in the clinical trial process., Data Sources: Literature searches were conducted in PubMed, the Cumulative Index to Nursing and Allied Health Literature, SCOPUS, Cochrane, and Web of Science from January 2009 to June 2021., Study Selection: Of 3592 records screened, 22 records investigating 27 unique health literacy interventions in randomized controlled studies were included for qualitative synthesis., Data Extraction: Data screening and abstraction were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines., Data Synthesis: Types of health literacy interventions were multimedia or technology-based (11 studies), simplification of written material (six studies) and in-person sessions (five studies). These interventions were applied at various stages in the healthcare and clinical trial process. All studies used unique outcome measures, including patient comprehension, quality of informed consent, and patient activation and engagement., Conclusions: The findings of our study suggest that best practice guidelines recommend health literacy interventions during the clinical trial process, presentation of information in multiple forms, involvement of patients in information optimization, and improved standardization in health literacy outcome measures., (Copyright © 2022. Published by Elsevier Inc.)

The COVID-19 pandemic has had widespread impact on healthcare, resulting in modifications to how we perform cancer research, including clinical trials for cancer. The impact of some healthcare workers and study coordinators working remotely and patients minimizing visits to medical facilities impacted clinical trial participation. Clinical trial accrual dropped at the onset of the pandemic, with improvement over time. Adjustments were made to some trial protocols, allowing telephone or video-enabled consent. Certain study activities were permitted to be performed by local healthcare providers or at local laboratories to maximize patients' ability to continue on study during these challenging times. We discuss the impact of COVID-19 on cancer clinical trials and changes at the local, cooperative group, and national level., (© 2021. Society of Surgical Oncology.)

Globally, high-throughput sequencing (HTS) has been used for virus detection in germplasm certification programs. However, sequencing costs have impeded its implementation as a routine diagnostic certification tool. In this study, the targeted genome sequencing (TG-Seq) approach was developed to simultaneously detect multiple (four) viral species of; Pea early browning virus (PEBV), Cucumber mosaic virus (CMV), Bean yellow mosaic virus (BYMV) and Pea seedborne mosaic virus (PSbMV). TG-Seq detected all the expected viral amplicons within multiplex PCR (mPCR) reactions. In contrast, the expected PCR amplicons were not detected by gel electrophoresis (GE). For example, for CMV, GE only detected RNA1 and RNA2 while TG-Seq detected all the three RNA components of CMV. In an mPCR to amplify all four viruses, TG-Seq readily detected each virus with more than 732,277 sequence reads mapping to each amplicon. In addition, TG-Seq also detected all four amplicons within a 10 -8 serial dilution that were not detectable by GE. Our current findings reveal that the TG-Seq approach offers significant potential and is a highly sensitive targeted approach for detecting multiple plant viruses within a given biological sample. This is the first study describing direct HTS of plant virus mPCR products. These findings have major implications for grain germplasm healthy certification programs and biosecurity management in relation to pathogen entry into Australia and elsewhere.

LAMP assays are targeted molecular tests for the rapid detection of species in the laboratory and field. We developed a LAMP assay for an economically important fruit fly species, Queensland fruit fly, Bactrocera tryoni. This assay was assessed against a broad panel of target and non-target species and found to be specific, only amplifying the target species and closest relatives, in a portable real-time fluorometer (Genie III) in under 15 minutes with an anneal derivative temperature of 82.5 o C. The assay is sensitive to low levels of target DNA (>0.016 ng/µl), performing equally to the existing qPCR test. To enable retention of a physical voucher specimen, for potential morphological confirmation of LAMP results, a novel whole-specimen non-destructive DNA extraction method was developed, suitable for LAMP in the field. The stability of DNA extraction and LAMP reagents was tested under simulated and actual field conditions and shown to be robust. Our new assay now provides a portable molecular tool for the detection of this significant tephritid fruit fly pest species of biosecurity/quarantine concern. This has already proven invaluable for in-field diagnostics, providing real-time support influencing immediate actions, with negative results allowing the release of fruit produce, and positive results initiating fruit fly control measures.

The aim of this study was to assess the development of personalized dentistry in the curricula of North American dental schools from 2014 to 2017. In 2014, a web-based survey on personalized medicine/dentistry (PM/PD) was distributed to academic deans of all U.S. (n=65) and Canadian (n=10) dental schools with graduating classes. The results (n=42; 56% response rate) showed that few schools had plans for implementation of PM/PD at the time, even though the majority of respondents reported feeling that PM/PD should be taught in the curriculum and will impact clinical practice in the future. A three-year followup survey in 2017, sent to the same 75 schools, was designed to reassess the teaching/practice of PM/PD in dental schools in both didactic and clinical curricula. In the results of the 2017 survey (n=30; 40% response rate), the majority of respondents reported feeling that PM/PD should be taught in dental curricula. However, while most respondents indicated their schools did not teach PM/PD as a portion of their didactic curricula, they reported that specific pertinent PM/PD topics were taught as part of other courses in their curricula. The 2017 survey also evaluated the use of seven genetics-based and eight non-genetics-based PM/PD diagnostics in the schools' clinical curricula. Overall, non-genetics-based diagnostics were used more often than genetics-based diagnostics, and the use of genetics-based diagnostics was more prevalent in postgraduate than predoctoral clinics. Personalized dentistry will inevitably be part of the dental professional's future and should be reflected in basic science research, clinical settings, and dental school curricula in both predoctoral and postgraduate programs.

Purpose: To identify the molecular cause in five unrelated families with a distinct autosomal dominant ocular systemic disorder we called ROSAH syndrome due to clinical features of retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and migraine headache., Methods: Independent discovery exome and genome sequencing in families 1, 2, and 3, and confirmation in families 4 and 5. Expression of wild-type messenger RNA and protein in human and mouse tissues and cell lines. Ciliary assays in fibroblasts from affected and unaffected family members., Results: We found the heterozygous missense variant in the ɑ-kinase gene, ALPK1, (c.710C>T, [p.Thr237Met]), segregated with disease in all five families. All patients shared the ROSAH phenotype with additional low-grade ocular inflammation, pancytopenia, recurrent infections, and mild renal impairment in some. ALPK1 was notably expressed in retina, retinal pigment epithelium, and optic nerve, with immunofluorescence indicating localization to the basal body of the connecting cilium of the photoreceptors, and presence in the sweat glands. Immunocytofluorescence revealed expression at the centrioles and spindle poles during metaphase, and at the base of the primary cilium. Affected family member fibroblasts demonstrated defective ciliogenesis., Conclusion: Heterozygosity for ALPK1, p.Thr237Met leads to ROSAH syndrome, an autosomal dominant ocular systemic disorder.

Antigen-binding fragments (Fab) and F(ab') 2 antibodies serve as alternative formats to full-length anti-bodies in therapeutic and immune assays. They provide the advantage of small size, short serum half-life, and lack of effector function. Several proteases associated with invasive diseases are known to cleave antibodies in the hinge-region, and this results in anti-hinge antibodies (AHA) toward the neoepitopes. The AHA can act as surrogate Fc and reintroduce the properties of the Fc that are otherwise lacking in antibody fragments. While this response is desired during the natural process of fighting disease, it is commonly unwanted for therapeutic antibody fragments. In our study, we identify a truncation in the lower hinge region of the antibody that maintains efficient proteolytic cleavage by IdeS protease. The resulting neoepitope at the F(ab') 2 C-terminus does not have detectable binding of pre-existing AHA, providing a practical route to produce F(ab') 2 in vitro by proteolytic digestion when the binding of pre-existing AHA is undesired. We extend our studies to the upper hinge region of the antibody and provide a detailed analysis of the contribution of C-terminal residues of the upper hinge of human IgG1, IgG2 and IgG4 to pre-existing AHA reactivity in human serum. While no pre-existing antibodies are observed toward the Fab of IgG2 and IgG4 isotype, a significant response is observed toward most residues of the upper hinge of human IgG1. We identify a T 225 L variant and the natural C-terminal D 221 as solutions with minimal serum reactivity. Our work now enables the production of Fab and F(ab') 2 for therapeutic and diagnostic immune assays that have minimal reactivity toward pre-existing AHA.

Background: To evaluate the aetiology of paediatric optic atrophy in an Australian population., Design: Retrospective review of medical records was conducted at The Children's Hospital at Westmead, Sydney, Australia., Participants: Two hundred twenty-seven subjects <16 years who were diagnosed with optic atrophy on fundoscopic examination between 1979 and 2015 were included in the study., Methods: Subjects were obtained from the hospital database, which codes diagnoses for all admissions, as well as the orthoptic department database, which codes diagnoses for ophthalmology department outpatients., Main Outcome Measures: The predominant cause for optic atrophy was assigned to each patient. Clinical presentation was defined as the principal reason for evaluation. Demographic data included gender, affected eye and age at diagnosis. Data on medical comorbidities (cerebral palsy, developmental delay, microcephaly and seizures) and ocular comorbidities (strabismus and nystagmus) were collected., Results: The mean age at initial eye review was 4.7 ± 4.4 years. There was bilateral optic atrophy in 81.5% of cases. Unilateral optic atrophy was largely due to tumours. When analysing over the three time periods, (1979-1990, 1991-2003 and 2004-2015), perinatal events (3.0%, 22.7% and 22.6%) and neurodegenerative disease (3.0%, 14.9% and 15.1%) are slowly replacing tumours (39.4%, 24.8% and 15.1%) as the top causes for paediatric optic atrophy. The incidence of other causes has remained fairly stable over time, albeit an increase in idiopathic causes., Conclusions: There has been shift in the etiological profile of optic atrophy. Whilst tumours are still an important cause of paediatric optic atrophy for an Australian population, perinatal events and neurodegenerative disease are becoming more significant., (© 2016 Royal Australian and New Zealand College of Ophthalmologists.)

Purpose: To evaluate outcomes of trabeculectomy bleb needle revision with 5-fluorouracil augmentation performed in the operating theater., Methods: Retrospective study of all patients undergoing trabeculectomy bleb needle revisions in the operating theater performed by a single surgeon in a metropolitan hospital in Australia. A total of 51 needle revisions were performed on 33 eyes over a mean follow-up time of 1.81±1.56 years., Results: A total of 29% achieved intraocular pressure (IOP) ≤20 mm Hg off all glaucoma medications, and an additional 39% achieved qualified success with the addition of glaucoma medications, giving overall success of 68%. Analyzing success rate for target IOP≤16 mm Hg, 24% achieved target off all glaucoma medications, 35% achieved qualified success with the addition of glaucoma medications, giving an overall success rate of 59%. There was a statistically significant improvement in IOP, as compared with preoperative levels, at all timepoints postoperatively (P<0.05). However, number of glaucoma medications remained unchanged (P>0.05) contributing to the high percentage of qualified successes. Visual acuity remained unchanged and there were no major postoperative complications. The Kaplan-Meier survival shows a survival rate of 60% with IOP≤20 mm Hg and 40% for IOP≤16 mm Hg at 5 years., Conclusions: Trabeculectomy needle revision is a useful option for the management of elevated IOP in the presence of a failed or failing trabeculectomy bleb. However, as with trabeculectomy, there tends to be a failure rate over time. This often leads to reinstitution of glaucoma medications and/or further needle revisions to maintain IOPs at target level. The procedure itself is minimally invasive with an acceptable safety profile.

We describe the case of an otherwise healthy 13-year-old boy who presented with blurred vision and deteriorating visual acuity in his left eye. Fundus examination showed left optic disk swelling, exudates, and hemorrhages. He was found to have an elevated left central retinal venous pressure to the level of arterial diastolic pressure, an elevated left central macular thickness and a prolonged disk-to-disk transit time on fluorescein angiography, which confirmed the diagnosis of unilateral central retinal vein occlusion (CRVO). The child was treated with one injection of bevacizumab. He has maintained visual acuity of 6/6 for 2 years following treatment, despite persistent elevated left central venous pressure and chronic optic disk edema., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

A number of viruses from the genera Furovirus, Hordeivirus and Rymovirus are known to infect and damage the four major temperate cereal crops, wheat, barley, sorghum and oats. Currently, there is no active testing in Australia for any of these viruses, which pose a significant biosecurity threat to the phytosanitary status of Australia's grains industry. To address this, broad spectrum PCR assays were developed to target virus species within the genera Furovirus, Hordeivirus and Rymovirus. Five sets of novel genus-specific primers were designed and tested in reverse-transcription polymerase chain reaction assays against a range of virus isolates in plant virus diagnostic laboratories in both Australia and New Zealand. Three of these assays were then chosen to screen samples in a three-year survey of cereal crops in western Victoria, Australia. Of the 8900 cereal plants screened in the survey, all were tested free of furoviruses, hordeiviruses and rymoviruses. To date, there were no published genus-specific primers available for the detection of furoviruses, hordeiviruses and rymoviruses. This study shows for the first time a broad-spectrum molecular test being used in a survey for exotic grain viruses in Australia. Results from this survey provide important evidence of the use of this method to demonstrate the absence of these viruses in Victoria, Australia. The primer pairs reported here are expected to detect a wide range of virus species within the three genera., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background/aims: Intravenous bisphosphonate therapy is the first-line treatment in moderate-to-severe osteogenesis imperfecta (OI), but there are varied treatment protocols with little data on long-term efficacy. This study evaluates the clinical outcomes when transitioning from active bisphosphonate treatment to maintenance therapy., Methods: A retrospective review was conducted on 17 patients before treatment, following active treatment (zoledronate 0.05 mg/kg 6-monthly or pamidronate 6-9 mg/kg/year) and after establishment on maintenance treatment for more than 2 years (zoledronate 0.025 mg/kg 6-monthly or pamidronate <4 mg/kg/year)., Results: There was a significant reduction in mean fracture rate from 1.5 ± 1.1 fractures/year at baseline to 0.7 ± 0.7 fractures/year on active treatment. Z-scores for lumbar spine bone mineral density, bone mineral content, volumetric bone mineral density and bone mineral content for lean tissue mass increased during active treatment. These improvements were maintained during the period of maintenance treatment. Vertebral height improved in fractured thoracic vertebrae from pre-treatment to active therapy and improved further during maintenance treatment. Metacarpal cortical thickness and relative cortical area also increased over the treatment periods., Conclusion: Maintenance intravenous bisphosphonate therapy preserved the beneficial effects of active treatment at the doses stated above. Further studies are required to determine the optimal bisphosphonate treatment regimen in the management of children with OI., (© 2015 S. Karger AG, Basel.)

Polymerase chain reaction (PCR) is used to detect groups of viruses with the use of group-specific degenerate primers. Inosine residues are sometimes used in the primers to match variable positions within the complementary target sequences, but there is little data on their effects on cDNA synthesis and amplification. A quantitative reverse-transcription PCR was used to measure the rate of amplification with primers containing inosine residues substituted at different positions and in increasing numbers. Experiments were conducted using standard quantities of cloned DNA copied from Potato virus Y genomic RNA and RNA (cRNA) transcribed from the cloned DNA. Single inosine residues had no affect on the amplification rate in the forward primer, except at one position close to the 3' terminus. Conversely, single inosine residues significantly reduced the amplification rate when placed at three out of four positions in the reverse primer. Four or five inosine substitutions could be tolerated with some decline in rates, but amplification often failed from cRNA templates with primers containing larger numbers of inosines. Greater declines in the rate of amplification were observed with RNA templates, suggesting that reverse transcription suffers more than PCR amplification when inosine is included in the reverse primer.

Unlabelled: Unknown and foreign viruses can be detected using degenerate primers targeted at conserved sites in the known viral gene sequences. Conserved sites are found by comparing sequences and so the usefulness of a set of primers depends crucially on how well the known sequences represent the target group including unknown sequences., Methodology/principal Findings: We developed a method for assessing the apparent stability of consensus sequences at sites over time using deposition dates from Genbank. We tested the method using 17 conserved sites in potyvirus genomes. The accumulation of knowledge of sequence variants over 20 years caused 'consensus decay' of the sites. Rates of decay were rapid at all sites but varied widely and as a result, the ranking of the most conserved sites changed. The discovery and reporting of sequences from previously unknown and distinct species, rather than from strains of known species, dominated the decay, indicating it was largely a sampling effect related to the progressive discovery of species, and recent virus mutation was probably only a minor contributing factor., Conclusion/significance: We showed that in the past, the sampling bias has misled the choice of the most conserved target sites for genus specific degenerate primers. The history of sequence discoveries indicates primer designs should be updated regularly and provides an additional dimension for improving the design of degenerate primers.