Comparison of four handheld point-of-care ultrasound devices by expert users.

BACKGROUND: Point-of-care ultrasound (POCUS) is rapidly becoming ubiquitous across healthcare specialties. This is due to several factors including its portability, immediacy of results to guide clinical decision-making, and lack of radiation exposure to patients. The recent growth of handheld ultrasound devices has improved access to ultrasound for many clinicians. Few studies have directly compared different handheld ultrasound devices among themselves or to cart-based ultrasound machines. We conducted a prospective observational study comparing four common handheld ultrasound devices for ease of use, image quality, and overall satisfaction. Twenty-four POCUS experts utilized four handheld devices (Butterfly iQ+™ by Butterfly Network Inc., Kosmos™ by EchoNous, Vscan Air™ by General Electric, and Lumify™ by Philips Healthcare) to obtain three ultrasound views on the same standardized patients using high- and low-frequency probes. RESULTS: Data were collected from 24 POCUS experts using all 4 handheld devices. No single ultrasound device was superior in all categories. For overall ease of use, the Vscan Air™ was rated highest, followed by the Lumify™. For overall image quality, Lumify™ was rated highest, followed by Kosmos™. The Lumify™ device was rated highest for overall satisfaction, while the Vscan Air™ was rated as the most likely to be purchased personally and carried in one's coat pocket. The top 5 characteristics of handheld ultrasound devices rated as being "very important" were image quality, ease of use, portability, total costs, and availability of different probes. CONCLUSIONS: In a comparison of four common handheld ultrasound devices in the United States, no single handheld ultrasound device was perceived to have all desired characteristics. POCUS experts rated the Lumify™ highest for image quality and Vscan Air™ highest for ease of use. Overall satisfaction was highest with the Lumify™ device, while the most likely to be purchased as a pocket device was the Vscan Air™. Image quality was felt to be the most important characteristic in evaluating handheld ultrasound devices.

Enteric Viruses and Pepper Mild Mottle Virus Show Significant Correlation in Select Mid-Atlantic Agricultural Waters.

Enteric viruses (EVs) are the largest contributors to foodborne illnesses and outbreaks globally. Their ability to persist in the environment, coupled with the challenges experienced in environmental monitoring, creates a critical aperture through which agricultural crops may become contaminated. This study involved a 17-month investigation of select human EVs and viral indicators in nontraditional irrigation water sources (surface and reclaimed waters) in the Mid-Atlantic region of the United States. Real-time quantitative PCR was used for detection of Aichi virus, hepatitis A virus, and norovirus genotypes I and II (GI and GII, respectively). Pepper mild mottle virus (PMMoV), a common viral indicator of human fecal contamination, was also evaluated, along with atmospheric (air and water temperature, cloud cover, and precipitation 24 h, 7 days, and 14 days prior to sample collection) and physicochemical (dissolved oxygen, pH, salinity, and turbidity) data, to determine whether there were any associations between EVs and measured parameters. EVs were detected more frequently in reclaimed waters (32% [n = 22]) than in surface waters (4% [n = 49]), similar to PMMoV detection frequency in surface (33% [n = 42]) and reclaimed (67% [n = 21]) waters. Our data show a significant correlation between EV and PMMoV (R2 = 0.628, P < 0.05) detection levels in reclaimed water samples but not in surface water samples (R2 = 0.476, P = 0.78). Water salinity significantly affected the detection of both EVs and PMMoV (P < 0.05), as demonstrated by logistic regression analyses. These results provide relevant insights into the extent and degree of association between human (pathogenic) EVs and water quality data in Mid-Atlantic surface and reclaimed waters, as potential sources for agricultural irrigation. IMPORTANCE Microbiological analysis of agricultural waters is fundamental to ensure microbial food safety. The highly variable nature of nontraditional sources of irrigation water makes them particularly difficult to test for the presence of viruses. Multiple characteristics influence viral persistence in a water source, as well as affecting the recovery and detection methods that are employed. Testing for a suite of viruses in water samples is often too costly and labor-intensive, making identification of suitable indicators for viral pathogen contamination necessary. The results from this study address two critical data gaps, namely, EV prevalence in surface and reclaimed waters of the Mid-Atlantic region of the United States and subsequent evaluation of physicochemical and atmospheric parameters used to inform the potential for the use of indicators of viral contamination.

Personalized balance games for children with cerebral palsy: A pilot study.

PURPOSE: To assess the changes in balance function in children with cerebral palsy (CP) after two weeks of daily training with personalized balance games. METHODS: Twenty-five children with CP, aged 5 to 18 years were randomly selected for experimental or control groups. Over a period of two weeks, all participants received 8-9 game sessions for 15-20 minutes, totaling 150-160 minutes. The experimental group used personalized balance games available from the GAmification for Better LifE (GABLE) online serious gaming platform. Children from the control group played Nintendo Wii games using a handheld Wii Remote. Both groups received the same background treatment. Recorded outcome measures were from a Trunk Control Measurement Scale (TCMS), Timed Up & Go Test (TUG), Center of Pressure Path Length (COP-PL), and Dynamic Balance Test (DBT). RESULTS: After two weeks of training in the experimental group TCMS scores increased by 4.5 points (SD = 3.5, p< 0.05) and DBT results increased by 0.88 points (IQR = 1.03, p< 0.05) while these scores did not change significantly in the control group. Overall, TUG and COP-PL scores were not affected in either group. CONCLUSION: This study demonstrates improvement of balancing function in children with CP after a two-week course of training with personalized rehabilitation computer games.

Preparing for a School-Located COVID-19 Vaccination Clinic.

School-located vaccination events (SLVE) have a long history in the United States and have successfully contributed to lower morbidity and mortality due to vaccine-preventable diseases. The school is an ideal place to reach children from all cultures, socioeconomic groups, and age-groups and is conveniently situated in communities for ease of accessibility for students, parents, and staff alike. School nurses play an important role in planning for SLVE and are ideally positioned to initiate this process and provide accurate information, dispelling myths about vaccines. Because school nurses are considered a trusted source of health information by the school community, they can provide valuable education on the impact of vaccination on student and staff attendance. Conducting a successful SLVE requires research, planning, and partnerships, and these partnerships are needed both within the school setting and outside this setting, within the community at large. The proliferation of the current COVID-19 pandemic and the subsequent vaccine production has caused school nurses to take the lead in preparing for mass vaccination clinics in order to help mitigate this serious public health threat. This manuscript describes the process a group of school nurses used to develop SLVE plans in response to a pandemic.

Temporal and Agricultural Factors Influence Escherichia coli Survival in Soil and Transfer to Cucumbers.

Biological soil amendments of animal origin (BSAAO) increase nutrient levels in soils to support the production of fruits and vegetables. BSAAOs may introduce or extend the survival of bacterial pathogens which can be transferred to fruits and vegetables to cause foodborne illness. Escherichia coli survival over 120 days in soil plots (3 m2) covered with (mulched) or without plastic mulch (not mulched), amended with either poultry litter, composted poultry litter, heat-treated poultry pellets, or chemical fertilizer, and transfer to cucumbers in 2 years (2018 and 2019) were evaluated. Plots were inoculated with E. coli (8.5 log CFU/m2) and planted with cucumber seedlings (Supremo). The number of days needed to reduce E. coli levels by 4 log CFU (dpi4log) was determined using a sigmoidal decline model. Random forest regression and one-way analysis of variance (ANOVA; P < 0.05) identified predictors (soil properties, nutrients, and weather factors) of dpi4log of E. coli and transfer to cucumbers. The combination of year, amendment, and mulch (25.0% increase in the mean square error [IncMSE]) and year (9.75% IncMSE) were the most prominent predictors of dpi4log and transfer to cucumbers, respectively. Nitrate levels at 30 days and soil moisture at 40 days were also impactful predictors of dpi4log. Differing rainfall amounts in 2018 (24.9 in.) and 2019 (12.6 in.) affected E. coli survival in soils and transfer to cucumbers. Salmonella spp. were recovered sporadically from various plots but were not recovered from cucumbers in either year. Greater transfer of E. coli to cucumbers was also shown to be partially dependent on dpi4log of E. coli in plots containing BSAAO.IMPORTANCE Poultry litter and other biological soil amendments are commonly used fertilizers in fruit and vegetable production and can introduce enteric pathogens such as Escherichia coli O157:H7 or Salmonella previously associated with outbreaks of illness linked to contaminated produce. E. coli survival duration in soils covered with plastic mulch or uncovered and containing poultry litter or heat-treated poultry litter pellets were evaluated. Nitrate levels on day 30 and moisture content in soils on day 40 on specific days were good predictors of E. coli survival in soils; however, the combination of year, amendment, and mulch type was a better predictor. Different cumulative rainfall totals from year to year most likely affected the transfer of E. coli from soils to cucumbers and survival durations in soil. E. coli survival in soils can be extended by the addition of several poultry litter-based soil amendments commonly used in organic production of fruits and vegetables and is highly dependent on temporal variation in rainfall.

A novel pathogenic missense ADAMTS17 variant that impairs secretion causes Weill-Marchesani Syndrome with variably dysmorphic hand features.

Weill-Marchesani syndrome (WMS) is a rare disorder displaying short stature, brachydactyly and joint stiffness, and ocular features including microspherophakia and ectopia lentis. Brachydactyly and joint stiffness appear less commonly in patients with WMS4 caused by pathogenic ADAMTS17 variants. Here, we investigated a large family with WMS from Newfoundland, Canada. These patients displayed core WMS features, but with proportionate hands that were clinically equivocal for brachydactyly. Whole exome sequencing and autozygosity mapping unveiled a novel pathogenic missense ADAMTS17 variant (c.3068 G > A, p.C1023Y). Sanger sequencing demonstrated variant co-segregation with WMS, and absence in 150 population matched controls. Given ADAMTS17 involvement, we performed deep phenotyping of the patients' hands. Anthropometrics applied to hand roentgenograms showed that metacarpophalangeal measurements of affected patients were smaller than expected for their age and sex, and when compared to their unaffected sibling. Furthermore, we found a possible sub-clinical phenotype involving markedly shortened metacarpophalangeal bones with intrafamilial variability. Transfection of the variant ADAMTS17 into HEK293T cells revealed significantly reduced secretion into the extracellular medium compared to wild-type. This work expands understanding of the molecular pathogenesis of ADAMTS17, clarifies the variable hand phenotype, and underscores a role for anthropometrics in characterizing sub-clinical brachydactyly in these patients.

Demonstration of a Longitudinal Medical Education Model (LMEM) Model to Teach Point-of-Care Ultrasound in Resource-Limited Settings.

Background: Short-term medical missions prevail as the most common form of international medical volunteerism, but they are ill-suited for medical education and training local providers in resource-limited settings. Objective: The purpose of this study is to evaluate the effectiveness of a longitudinal educational program in training clinicians how to perform point-of-care ultrasound (POCUS) in resource-limited clinics. Design: A retrospective study of a four-month POCUS training program was conducted with clinicians from a rural hospital in Haiti. The model included one-on-one, in-person POCUS teaching sessions by volunteer instructors from the United States and Europe. The Haitian trainees were assessed at the start of the program and at its conclusion by a direct objective structured clinical examination (OSCE), administered by the visiting instructors, with similar pre- and post- program ultrasound competency assessments. Results: Post-intervention, a significant improvement in POCUS competency was observed across six different fundamental areas of ultrasound (p < 0.0001). According to our objective structured clinical examination (OSCE), the mean assessment score increased from 0.47 to 1.68 out of a maximum score of 2 points, and each trainee showed significant overall improvement in POCUS competency independent of the initial competency pre-training (p < 0.005). There was a statistically significant improvement in POCUS application for five of the six medically relevant assessment categories tested. Conclusion: Our results provide a proof-of-concept for the longitudinal education-centered healthcare delivery framework in a resource-limited setting. Our longitudinal model provides local healthcare providers the skills to detect and diagnose significant pathologies, thereby reducing avoidable morbidity and mortality at little or no addition cost or risk to the patient. Furthermore, training local physicians obviates the need for frequent volunteering trips, saving costs in healthcare training and delivery.

Point-of-Care Ultrasound for Hospitalists: A Position Statement of the Society of Hospital Medicine.

Many hospitalists incorporate point-of-care ultrasound (POCUS) into their daily practice to answer specific diagnostic questions or to guide performance of invasive bedside procedures. However, standards for hospitalists in POCUS training and assessment are not yet established. Most internal medicine residency training programs, the major pipeline for incoming hospitalists, have only recently begun to incorporate POCUS in their curricula. The purpose of this document is to inform a broad audience on what POCUS is and how hospitalists are using it. This document is intended to provide guidance for the hospitalists who use POCUS and administrators who oversee its use. We discuss POCUS 1) applications, 2) training, 3) assessments, and 4) program management. Practicing hospitalists must continue to collaborate with their local credentialing bodies to outline requirements for POCUS use. Hospitalists should be integrally involved in decision-making processes surrounding POCUS program management.

Novel 25 kb Deletion of MERTK Causes Retinitis Pigmentosa With Severe Progression.

Purpose: Retinitis pigmentosa (RP) describes a complex group of inherited retinal dystrophies with almost 300 reported genes and loci. We investigated the genetic etiology of autosomal recessive RP (arRP) in a large kindred with 5 affected family members, who reside on the island of Newfoundland, Canada. Methods: Genetic linkage analysis was performed on 12 family members (Infinium HumanOmni2.5-8 BeadChip). Whole exome sequencing analysis (Illumina HiSeq) was performed on one affected individual. A custom pipeline was applied to call, annotate, and filter variants. FishingCNV was used to scan the exome for rare copy number variants (CNVs). Candidate CNVs subsequently were visualized from microarray data (CNVPartition v.3.1.6.). MERTK breakpoints were mapped and familial cosegregation was tested using Sanger Sequencing. Results: We found strong evidence of linkage to a locus on chromosome 2 (logarithm of the odds [LOD] 4.89 [θ = 0]), at an interval encompassing the MERTK gene. Whole exome sequencing did not uncover candidate point mutations in MERTK, or other known RP genes. Subsequently, CNV analysis of the exome data and breakpoint mapping revealed a 25,218 bp deletion of MERTK, encompassing exons 6 to 8, with breakpoints in introns 5 (chr2:112,725,292) and 8 (chr2:112,750,421). A 48 bp insertion sequence was buried within the breakpoint; 18 bps shared homology to MIR4435-2HG and LINC00152, and 30 bp mapped to MERTK. The deletion cosegregated with arRP in the family. Conclusions: This study describes the molecular and clinical characterization of an arRP family segregating a novel 25 kb deletion of MERTK. These findings may assist clinicians in providing a diagnosis for other unsolved RP cases.

An improved computational constitutive model for glass.

In 2011, Holmquist and Johnson presented a model for glass subjected to large strains, high strain rates and high pressures. It was later shown that this model produced solutions that were severely mesh dependent, converging to a solution that was much too strong. This article presents an improved model for glass that uses a new approach to represent the interior and surface strength that is significantly less mesh dependent. This new formulation allows for the laboratory data to be accurately represented (including the high tensile strength observed in plate-impact spall experiments) and produces converged solutions that are in good agreement with ballistic data. The model also includes two new features: one that decouples the damage model from the strength model, providing more flexibility in defining the onset of permanent deformation; the other provides for a variable shear modulus that is dependent on the pressure. This article presents a review of the original model, a description of the improved model and a comparison of computed and experimental results for several sets of ballistic data. Of special interest are computed and experimental results for two impacts onto a single target, and the ability to compute the damage velocity in agreement with experiment data.This article is part of the themed issue 'Experimental testing and modelling of brittle materials at high strain rates'.

Dietary modulation of the microbiome affects autoinflammatory disease.

The incidences of chronic inflammatory disorders have increased considerably over the past three decades. Recent shifts in dietary consumption may have contributed importantly to this surge, but how dietary consumption modulates inflammatory disease is poorly defined. Pstpip2(cmo) mice, which express a homozygous Leu98Pro missense mutation in the Pombe Cdc15 homology family protein PSTPIP2 (proline-serine-threonine phosphatase interacting protein 2), spontaneously develop osteomyelitis that resembles chronic recurrent multifocal osteomyelitis in humans. Recent reports demonstrated a crucial role for interleukin-1ß (IL-1ß) in osteomyelitis, but deletion of the inflammasome components caspase-1 and NLRP3 failed to rescue Pstpip2(cmo) mice from inflammatory bone disease. Thus, the upstream mechanisms controlling IL-1ß production in Pstpip2(cmo) mice remain to be identified. In addition, the environmental factors driving IL-1ß-dependent inflammatory bone erosion are unknown. Here we show that the intestinal microbiota of diseased Pstpip2(cmo) mice was characterized by an outgrowth of Prevotella. Notably, Pstpip2(cmo) mice that were fed a diet rich in fat and cholesterol maintained a normal body weight, but were markedly protected against inflammatory bone disease and bone erosion. Diet-induced protection against osteomyelitis was accompanied by marked reductions in intestinal Prevotella levels and significantly reduced pro-IL-1ß expression in distant neutrophils. Furthermore, pro-IL-1ß expression was also decreased in Pstpip2(cmo) mice treated with antibiotics, and in wild-type mice that were kept under germ-free conditions. We further demonstrate that combined deletion of caspases 1 and 8 was required for protection against IL-1ß-dependent inflammatory bone disease, whereas the deletion of either caspase alone or of elastase or neutrophil proteinase 3 failed to prevent inflammatory disease. Collectively, this work reveals diet-associated changes in the intestinal microbiome as a crucial factor regulating inflammasome- and caspase-8-mediated maturation of IL-1ß and osteomyelitis in Pstpip2(cmo) mice.

The prevalence of human papillomavirus and its impact on cervical dysplasia in Northern Canada.

INTRODUCTION: Certain types of the Human Papillomavirus (HPV) are sexually transmitted and highly associated with development of cervical dysplasia and cervical cancer but the distribution of HPV infection in the North, particularly amongst First Nations, Metis, and Inuit peoples, is little known. The purposes of the study are to identify the prevalence of type-specific HPV infections and the association of different HPV types with cervical dysplasia among women in Northern Canada. METHODS: This was a cross-sectional study with attendants of the routine or scheduled Pap testing program in the Northwest Territories (NWT), Nunavut, Labrador and Yukon, Canada. Approximately half of each sample was used for Pap test and the remaining was used for HPV genotyping using a Luminex-based method. Pap test results, HPV types, and demographic information were linked for analyses. RESULTS: Results from 14,598 specimens showed that HPV infection was approximately 50% higher among the Aboriginal than the non-Aboriginal population (27.6% vs. 18.5%). Although the most common HPV type detected was HPV 16 across region, the prevalence of other high risk HPV types was different. The age-specific HPV prevalence among Aboriginal showed a 'U' shape which contrasted to non-Aboriginal. The association of HPV infection with cervical dysplasia was similar in both Aboriginal and non-Aboriginal populations. CONCLUSIONS: The HPV prevalence was higher in Northern Canada than in other Areas in Canada. The prevalence showed a higher rate of other high risk HPV infections but no difference of HPV 16/18 infections among Aboriginal in comparison with non-Aboriginal women. This study provides baseline information on HPV prevalence that may assist in surveillance and evaluation systems to track and assess HPV vaccine programs.

RIP1-driven autoinflammation targets IL-1α independently of inflammasomes and RIP3.

The protein-tyrosine phosphatase SHP-1 has critical roles in immune signalling, but how mutations in SHP-1 cause inflammatory disease in humans remains poorly defined. Mice homozygous for the Tyr208Asn amino acid substitution in the carboxy terminus of SHP-1 (referred to as Ptpn6(spin) mice) spontaneously develop a severe inflammatory syndrome that resembles neutrophilic dermatosis in humans and is characterized by persistent footpad swelling and suppurative inflammation. Here we report that receptor-interacting protein 1 (RIP1)-regulated interleukin (IL)-1α production by haematopoietic cells critically mediates chronic inflammatory disease in Ptpn6(spin) mice, whereas inflammasome signalling and IL-1ß-mediated events are dispensable. IL-1α was also crucial for exacerbated inflammatory responses and unremitting tissue damage upon footpad microabrasion of Ptpn6(spin) mice. Notably, pharmacological and genetic blockade of the kinase RIP1 protected against wound-induced inflammation and tissue damage in Ptpn6(spin) mice, whereas RIP3 deletion failed to do so. Moreover, RIP1-mediated inflammatory cytokine production was attenuated by NF-κB and ERK inhibition. Together, our results indicate that wound-induced tissue damage and chronic inflammation in Ptpn6(spin) mice are critically dependent on RIP1-mediated IL-1α production, whereas inflammasome signalling and RIP3-mediated necroptosis are dispensable. Thus, we have unravelled a novel inflammatory circuit in which RIP1-mediated IL-1α secretion in response to deregulated SHP-1 activity triggers an inflammatory destructive disease that proceeds independently of inflammasomes and programmed necrosis.

Molecular genetics of achromatopsia in Newfoundland reveal genetic heterogeneity, founder effects and the first cases of Jalili syndrome in North America.

Achromatopsia (ACHM) is a severe retinal disorder characterized by an inability to distinguish colors, impaired visual acuity, photophobia and nystagmus. This rare autosomal recessive disorder of the cone photoreceptors is best known for its increased frequency due to founder effect in the Pingelapese population of the Pacific islands. Sixteen patients from Newfoundland, Canada were sequenced for mutations in the four known achromatopsia genes CNGA3, CNGB3, GNAT2, and PDE6C. The majority (n = 12) of patients were either homozygotes or compound heterozygotes for known achromatopsia alleles, two in CNGB3 (p.T383fsX and p.T296YfsX9) and three in CNGA3 (p.R283Q, p.R427C and p.L527R). Haplotype reconstruction showed that recurrent mutations p.T383fsX and p.L527R were due to a founder effect. Aggregate data from exome sequencing, segregation analysis and archived medical records support a rediagnosis of Jalili syndrome in affected siblings (n = 4) from Family 0094, which to our knowledge is the first family identified with Jalili Syndrome in North America.

Factors associated with human papillomavirus infection among women in the Northwest Territories.

BACKGROUND: In some regions, Aboriginal women have higher rates of cervical cancer compared to other Canadian women. However, little data are available regarding the co-factors of HPV infection in the Aboriginal population of Canada. We examined factors associated with high-risk human papillomavirus (HR-HPV) infection in a population of women (both Aboriginal and non-Aboriginal) in the Northwest Territories (NWT). METHODS: We used a cross-sectional design using a convenience sample of all women aged 14 years or older presenting for Papanicolaou (Pap) testing across all regions of the NWT from March 2009 to March 2010. Women answered a questionnaire on demographic characteristics, sexual behaviour, and gynaecological and obstetrical events. We used multiple regression analysis to explore factors associated with HR-HPV infection according to age and cultural background. HPV typing was done using the Luminex assay. RESULTS: Of the total 1,279 participants, 178 had missing HPV results. We obtained data on 1,101 women and overall HR-HPV prevalence was 14.2%. Younger age, single marital status, Aboriginal background, current smoking, lifetime deliveries, use of hormonal contraceptives, and the numbers of sexual partners in the last year were associated with prevalent HR-HPV. DISCUSSION: Our findings tend to indicate that Aboriginal women have different predictors of HR-HPV than non-Aboriginal women that may affect HPV progression to cervical cancer. These findings can help to better target public health practices for the women at higher risk of HPV infection and cervical cancer.

Primary angle closure glaucoma in East Asia: educational attainment as a protective factor.

PURPOSE: To examine the relationship between education, other risk factors and incident primary angle closure glaucoma (PACG). METHOD: Glaucoma was excluded in a group of 4597 Mongolian volunteers in 1999. After 6 years, 1892 traced participants had full ophthalmic examination, dilated disc photographs and agreed to complete a questionnaire on socio-economic status. PACG was diagnosed using both structural and functional evidence from objective grading of paired disc photographs, follow up visual fields and clinical examination. Ophthalmic examination included van Herick grading, Goldmann intraocular pressure (IOP), gonioscopy, lens opacity grading and dilated disc examination. Central anterior chamber depth, lens thickness and axial length were recorded using ultrasound A scan mounted on a slitlamp. Education level was assessed using national census categories. RESULTS: PACG was diagnosed in 29 participants (6 year incidence = 1.53%, 95% confidence interval (CI) = 1.03-2.19%). In univariate analysis, risk factors for incident PACG included presence of refractive error, narrow van Herick grading of ≤15%, narrower average Shaffer grading, higher IOP, larger cup disc ratio and lower levels of education. In multivariate analysis, adjusted for age, sex, Shaffer grading, refractive error and IOP, those with no formal education were approximately 7 times more likely to develop PACG compared to those with >8 years of formal schooling (OR = 7.27, 95% CI = 2.73-19.38). CONCLUSIONS: People with lower levels of education have a higher risk of incident PACG, independent of age, sex, IOP and axial length.

Influence of Methylobacterium on iron translocation in plants.

Iron metabolism in plants is essential to maintain optimal growth and iron nutrition is dependent on uptake of iron from the environment and movement of iron in the plant tissues. We have examined the translocation of iron in plant leaves following foliar application of FeEDTA to Vicia faba and Zea mays. Using radiolabeled iron, we observed that iron translocation is stimulated by products of Methylobacterium mesophylicum and by the cytokinin, kinetin. When cytokinins were applied to leaves along with (55)FeEDTA, the rate of iron translocation was greater than in controls without cytokinin addition. Since recent studies indicate that M. mesophylicum is widely distributed in the environment as a pyllospheric bacterium, this organism may have an important role in enhancing translocation of nutrients in plant leaves.

A novel, non-stop mutation in FOXE3 causes an autosomal dominant form of variable anterior segment dysgenesis including Peters anomaly.

Anterior segment dysgenesis (ASD) is a spectrum of disorders that affect the anterior ocular chamber. Clinical studies on a Newfoundland family over the past 30 years show that 11 relatives have a variable ocular phenotype ranging from microcornea to Peters anomaly, segregating as an autosomal dominant trait. To determine the molecular etiology of the variable ASD in this family, we sequenced nine functional candidate genes and identified 44 variants. A point mutation in FOXE3, which codes for a transcription factor involved in the formation of the lens and surrounding structures, co-segregated with the variable ocular phenotype. This novel mutation (c.959G>T) substitutes the stop codon for a leucine residue, predicting the addition of 72 amino acids to the C-terminus of FOXE3. Two recent reports have also identified non-stop mutations in FOXE3 in patients with variable ocular phenotypes and predict an extended protein. Although FOXE3 is a lens-specific gene, we successfully isolated complementary DNA from lymphoblasts of an affected family member, and our sequencing results show that the c.959T allele is absent, suggesting that it may be degraded at the RNA level. Though preliminary, our results challenge the notion that an extended FOXE3 protein causes ASD, and instead suggests a mechanism of haploinsufficiency in the case of non-stop mutations. This study adds to several reports that suggest that autosomal-dominant mutations within FOXE3 cause ASD and has important clinical utility, especially for the diagnosis of mildly affected patients.

Randomised controlled trial of screening and prophylactic treatment to prevent primary angle closure glaucoma.

AIMS: To determine if screening with an ultrasound A-scan and prophylactic treatment of primary angle closure (PAC) with laser peripheral iridotomy (LPI) can reduce the incidence of primary angle closure glaucoma (PACG) in Mongolia. METHODS: A single-masked randomised controlled trial was initiated in 1999. 4725 volunteer Mongolian participants ≥ 50 years old from the capital Ulaanbaatar or the rural province of Bayankhongor were recruited, of which 128 were excluded with glaucoma. 4597 were randomly allocated to the control, no-screening arm or screening with ultrasound central anterior chamber depth (cACD), with the cut-off set at < 2.53 mm. 685 screen-positive participants were examined and angle closure was identified by gonioscopy in 160, of which 156 were treated with prophylactic LPI. Primary outcome of incident PACG was determined using both structural and functional evidence from objective grading of paired disc photographs from baseline and follow-up, objective grading of follow-up visual fields and clinical examination. RESULTS: Six years later, 801 (17.42%) participants were known to have died, and a further 2047 (53.92%) were traced and underwent full ophthalmic examination. In an intention to treat analysis using available data, PACG was diagnosed in 33 participants (1.61%, 95% CI 1.11% to 2.25%), of which 19 were in the screened group and 14 in the non-screened group (OR 1.29, 95% CI 0.65 to 2.60, p = 0.47), indicating no difference between groups. CONCLUSIONS: We were not able to identify a reduction in the 6 year incidence of PACG after screening with cACD < 2.53 mm and prophylactic treatment of PAC.

A comparison of ziprasidone and risperidone in the long-term treatment of schizophrenia: a 44-week, double-blind, continuation study.

OBJECTIVE: This randomized, double-blind, multicentre extension study compared the efficacy, tolerability, and safety of ziprasidone and risperidone for schizophrenia or schizoaffective disorder. METHODS: Patients who had responded to treatment for an acute exacerbation of illness in an 8-week study received ziprasidone, 80 to 160 mg/day (n = 62), or risperidone, 6 to 10 mg/day (n = 77), for up to 44 additional weeks. Primary efficacy variables included changes in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impression Severity (CGI-S) score. Tolerability and safety assessments included movement disorders, adverse events, study discontinuation rates, and weight and metabolic parameters. RESULTS: Both the ziprasidone and risperidone groups showed statistical improvement from baseline in PANSS and CGI-S scores at study end point with no significant differences between treatment groups. More risperidone-treated patients completed the study (41.6%) than ziprasidone-treated patients (33.9%), but the difference was not statistically significant. Ziprasidone-treated patients who completed the study showed greater improvement in depressive symptoms assessed by Montgomery and Asberg Depression Rating Scale than risperidone-treated patients (P < 0.05). Ziprasidone was associated with a more favourable effect on extrapyramidal symptom (EPS) measures and prolactin as well as less weight gain than risperidone. Median dosages were ziprasidone 120 mg/day and risperidone 8 mg/day. CONCLUSIONS: Ziprasidone and risperidone demonstrated similar efficacy during long-term treatment of patients with schizophrenia or schizoaffective disorder. While more subjects on risperidone completed the extension study, ziprasidone was associated with fewer adverse effects on weight, EPS measures, and prolactin than risperidone.