Listeria monocytogenes Illness and Deaths Associated With Ongoing Contamination of a Multiregional Brand of Ice Cream Products, United States, 2010-2015.

BACKGROUND: Frozen foods have rarely been linked to Listeria monocytogenes illness. We describe an outbreak investigation prompted by both hospital clustering of illnesses and product testing. METHODS: We identified outbreak-associated listeriosis cases using whole-genome sequencing (WGS), product testing results, and epidemiologic linkage to cases in the same Kansas hospital. We reviewed hospital medical and dietary records, product invoices, and molecular subtyping results. Federal and state officials tested product and environmental samples for L. monocytogenes. RESULTS: Kansas officials were investigating 5 cases of listeriosis at a single hospital when, simultaneously, unrelated sampling for a study in South Carolina identified L. monocytogenes in Company A ice cream products made in Texas. Isolates from 4 patients and Company A products were closely related by WGS, and the 4 patients with known exposures had consumed milkshakes made with Company A ice cream while hospitalized. Further testing identified L. monocytogenes in ice cream produced in a second Company A production facility in Oklahoma; these isolates were closely related by WGS to those from 5 patients in 3 other states. These 10 illnesses, involving 3 deaths, occurred from 2010 through 2015. Company A ultimately recalled all products. CONCLUSIONS: In this US outbreak of listeriosis linked to a widely distributed brand of ice cream, WGS and product sampling helped link cases spanning 5 years to 2 production facilities, indicating longstanding contamination. Comprehensive sanitation controls and environmental and product testing for L. monocytogenes with regulatory oversight should be implemented for ice cream production.

Anatomical and molecular characterization of some rhigonematid parasites of millipedes in Nigeria, with new insights into their phylogeny.

Parasitic nematodes of millipedes from Nigeria are molecularly characterized for the first time. During nematode surveys on live giant African millipedes from several localities in Nigeria, 4 species of rhigonematids were identified by application of integrative taxonomical approaches (morpho-anatomy and molecular markers), including Brumptaemilius sp., Gilsonema gabonensis, Obainia pachnephorus, and Rhigonema disparovis. The results of morphometric and molecular analyses of D2-D3 28S, ITS, partial 18S rRNA, and cytochrome oxidase c subunit 1 (COI) gene sequences further characterized the rhigonematid species, and clearly separated them from other related species. Phylogenetic relationships based on 28S and 18S rRNA genes suggest that genera within Ransomnematoidea (Ransomnema, Heth, Carnoya, Brumptaemilius, Cattiena, Insulanema, Gilsonema) and Rhigonematoidea (Rhigonema, Obainia, Xystrognathus, Trachyglossoides, Ichthyocephaloides) clustered rather closer than could be expected in view of their morphological differences. Phylogenetic relationships based on ITS and COI are congruent with those of other ribosomal genes; however, they are not conclusive due to the scarcity of available sequences of these genes for these genera in NCBI.

Improved tolerability of neratinib in patients with HER2-positive early-stage breast cancer: the CONTROL trial.

BACKGROUND: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for extended adjuvant treatment in early-stage HER2-positive breast cancer based on the phase III ExteNET study. In that trial, in which no antidiarrheal prophylaxis was mandated, grade 3 diarrhea was observed in 40% of patients and 17% discontinued due to diarrhea. The international, open-label, sequential-cohort, phase II CONTROL study is investigating several strategies to improve tolerability. PATIENTS AND METHODS: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year plus loperamide prophylaxis (days 1-28 or 1-56). Sequential cohorts evaluated additional budesonide or colestipol prophylaxis (days 1-28) and neratinib dose escalation (DE; ongoing). The primary end point was the incidence of grade ≥3 diarrhea. RESULTS: Final data for loperamide (L; n = 137), budesonide + loperamide (BL; n = 64), colestipol + loperamide (CL; n = 136), and colestipol + as-needed loperamide (CL-PRN; n = 104) cohorts, and interim data for DE (n = 60; completed ≥six cycles or discontinued; median duration 11 months) are available. No grade 4 diarrhea was observed. Grade 3 diarrhea rates were lower than ExteNET in all cohorts and lowest in DE (L 31%, BL 28%, CL 21%, CL-PRN 32%, DE 15%). Median number of grade 3 diarrhea episodes was one; median duration per grade 3 episode was 1.0-2.0 days across cohorts. Most grade 3 diarrhea and diarrhea-related discontinuations occurred in month 1. Diarrhea-related discontinuations were lowest in DE (L 20%, BL 8%, CL 4%, CL-PRN 8%, DE 3%). Decreases in health-related quality of life did not cross the clinically important threshold. CONCLUSIONS: Neratinib tolerability was improved with preemptive prophylaxis or DE, which reduced the rate, severity, and duration of neratinib-associated grade ≥3 diarrhea compared with ExteNET. Lower diarrhea-related treatment discontinuations in multiple cohorts indicate that proactive management can allow patients to stay on neratinib for the recommended time period. CLINICALTRIALS.GOV: NCT02400476.

Trends in County-Level COVID-19 Incidence in Counties With and Without a Mask Mandate - Kansas, June 1-August 23, 2020.

Wearing masks is a CDC-recommended* approach to reduce the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), by reducing the spread of respiratory droplets into the air when a person coughs, sneezes, or talks and by reducing the inhalation of these droplets by the wearer. On July 2, 2020, the governor of Kansas issued an executive order† (state mandate), effective July 3, requiring masks or other face coverings in public spaces. CDC and the Kansas Department of Health and Environment analyzed trends in county-level COVID-19 incidence before (June 1-July 2) and after (July 3-August 23) the governor's executive order among counties that ultimately had a mask mandate in place and those that did not. As of August 11, 24 of Kansas's 105 counties did not opt out of the state mandate§ or adopted their own mask mandate shortly before or after the state mandate was issued; 81 counties opted out of the state mandate, as permitted by state law, and did not adopt their own mask mandate. After the governor's executive order, COVID-19 incidence (calculated as the 7-day rolling average number of new daily cases per 100,000 population) decreased (mean decrease of 0.08 cases per 100,000 per day; net decrease of 6%) among counties with a mask mandate (mandated counties) but continued to increase (mean increase of 0.11 cases per 100,000 per day; net increase of 100%) among counties without a mask mandate (nonmandated counties). The decrease in cases among mandated counties and the continued increase in cases in nonmandated counties adds to the evidence supporting the importance of wearing masks and implementing policies requiring their use to mitigate the spread of SARS-CoV-2 (1-6). Community-level mitigation strategies emphasizing wearing masks, maintaining physical distance, staying at home when ill, and enhancing hygiene practices can help reduce transmission of SARS-CoV-2.

Monogenic cerebral small-vessel diseases: diagnosis and therapy. Consensus recommendations of the European Academy of Neurology.

BACKGROUND AND PURPOSE: Guidelines on monogenic cerebral small-vessel disease (cSVD) diagnosis and management are lacking. Endorsed by the Stroke and Neurogenetics Panels of the European Academy of Neurology, a group of experts has provided recommendations on selected monogenic cSVDs, i.e. cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL), autosomal dominant High Temperature Requirement A Serine Peptidase 1 (HTRA1), cathepsin-A-related arteriopathy with strokes and leukoencephalopathy (CARASAL), pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL), Fabry disease, mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) and type IV collagen (COL4)A1/2. METHODS: We followed the Delphi methodology to provide recommendations on several unanswered questions related to monogenic cSVD, including genetic testing, clinical and neuroradiological diagnosis, and management. RESULTS: We have proposed 'red-flag' features suggestive of a monogenic disease. General principles applying to the management of all cSVDs and specific recommendations for the individual forms of monogenic cSVD were agreed by consensus. CONCLUSIONS: The results provide a framework for clinicians involved in the diagnosis and management of monogenic cSVD. Further multicentre observational and treatment studies are still needed to increase the level of evidence supporting our recommendations.

How efficient is modern peri-urban nitrogen cycling: A case study.

Urban centres acquire and accumulate many materials from their hinterland, among these are nutrient elements such as nitrogen (N). The popular North American vision of a peri-urban setting is one where urban food production, composting and re-cycling are assumed to limit urban accumulation of nutrients. This study quantifies this assumption using the Lower Fraser Valley (LFV) of British Columbia as an example, ideal because it is surrounded by mountains, ocean and an international border which collectively delimit the peri-urban boundaries. Nitrogen influxes are dominated by livestock feed imports to support dairy and poultry production (18000 tonnes N), followed by human food imports (9210 tonnes N), as well as 5410 tonnes N as fertilizer and 4690 tonnes N in atmospheric deposition. There is a transfer of 6700 tonnes N from agricultural to urban ecosystems displacing food imports, but food production contributes to the N footprint of the LFV. Nitrogen effluxes are dominated by sewage disposal (10400 tonnes N), solid waste disposal (7020 tonnes N) and atmospheric emissions (9460 tonnes N). The total influx is 15 kg N per person, the net influx is 3.1 kg N per person. Per unit land area, these are a total influx of 24 kg N/ha and a net influx of 4.7 kg N/ha. The atmospheric emissions are 4.7 kg N per person and 7.2 kg/ha. The N in soil is mobile and it is assumed soil N is at a steady state concentration, thus the surplus N is lost from the soil, probably by leaching and runoff. The Fraser River is estimated to acquire and transport 5230 tonnes N from the region into the ocean each year, in addition to 10300 tonnes N from sewage outfall. This is coupled with effluxes of phosphorus (estimated previously), and the result probably has an impact on the coastal waters. There is little reuse of imported N and current waste management practices including composting and combustion do little to improve N efficiency.

Clinical efficacy of a next-generation sequencing gene panel for primary immunodeficiency diagnostics.

Primary immunodeficiencies (PIDs) are rare monogenic inborn errors of immunity that result in impairment of functions of the human immune system. PIDs have a broad phenotype with increased morbidity and mortality, and treatment choices are often complex. With increased accessibility of next-generation sequencing (NGS), the rate of discovery of genetic causes for PID has increased exponentially. Identification of an underlying monogenic diagnosis provides important clinical benefits for patients with the potential to alter treatments, facilitate genetic counselling, and pre-implantation diagnostics. We investigated a NGS PID panel of 242 genes within clinical care across a range of PID phenotypes. We also evaluated Phenomizer to predict causal genes from human phenotype ontology (HPO) terms. Twenty-seven participants were recruited, and a total of 15 reportable variants were identified in 48% (13/27) of the participants. The panel results had implications for treatment in 37% (10/27) of participants. Phenomizer identified the genes harbouring variants from HPO terms in 33% (9/27) of participants. This study shows the clinical efficacy that genetic testing has in the care of PID. However, it also highlights some of the disadvantages of gene panels in the rapidly moving field of PID genomics and current challenges in HPO term assignment for PID.

Availability of Phosphorus after Long-term Whole and Separated Slurry Application to Perennial Grass prior to Corn Silage.

Removing solids from whole dairy slurry (WS) can reduce P loading on fields. This study investigated the effects of 11 yr of applications of WS, separated liquid fraction (LF), commercial fertilizer, WS plus fertilizer, and a control on total and extractable (Kelowna) soil P in perennial grass ( Schreb.) and two subsequent silage corn ( L.) crops. Plots received 200 kg N ha with or without 40 kg P ha. Shoot biomass, P uptake, arbuscular mycorrhizal fungi root colonization, and soil microbial P were determined for corn at six leaves. Whole-crop and grain yield, P uptake, dry matter, and grain content were determined at maturity. The LF treatment received 30% less manure P than WS, had lower extractable soil P at 0 to 15 and 15 to 30 cm, and had lower total P at 0 to 15 cm. Historical treatments had no effect on soil microbial P or arbuscular mycorrhizal fungi colonization. At six leaves, corn shoot biomass, P concentration, and P uptake were related to historical P rates in Year 2, but the relationship was not apparent in Year 1. Starter P fertilizer increased shoot yield and P uptake for all treatments in both years. At maturity, most yield parameters for WS and LF were similar in Year 1, but in Year 2, there was a significant response to starter P fertilizer and a positive relationship between historical P rate and corn performance. This study shows that long-term LF treatments reduced the risk of P pollution with relatively little effect on the P response of subsequent corn crops.

Fatigue and cognitive function in systemic lupus erythematosus: associations with white matter microstructural damage. A diffusion tensor MRI study and meta-analysis.

Objective The objective of this study was to investigate fatigue and cognitive impairments in systemic lupus erythematous (SLE) in relation to diffuse white matter microstructural brain damage. Methods Diffusion tensor MRI, used to generate biomarkers of brain white matter microstructural integrity, was obtained in patients with SLE and age-matched controls. Fatigue and cognitive function were assessed and related to SLE activity, clinical data and plasma biomarkers of inflammation and endothelial dysfunction. Results Fifty-one patients with SLE (mean age 48.8 ± 14.3 years) were included. Mean diffusivity (MD) was significantly higher in all white matter fibre tracts in SLE patients versus age-matched healthy controls ( p < 0.0001). Fatigue in SLE was higher than a normal reference range ( p < 0.0001) and associated with lower MD ( ß = -0.61, p = 0.02), depression ( ß = 0.17, p = 0.001), anxiety ( ß = 0.13, p = 0.006) and higher body mass index ( ß = 0.10, p = 0.004) in adjusted analyses. Poorer cognitive function was associated with longer SLE disease duration ( p = 0.003) and higher MD ( p = 0.03) and, in adjusted analysis, higher levels of IL-6 ( ß = -0.15, p = 0.02) but not with MD. Meta-analysis (10 studies, n = 261, including the present study) confirmed that patients with SLE have higher MD than controls. Conclusion Patients with SLE have more microstructural brain white matter damage for age than the general population, but this does not explain increased fatigue or lower cognition in SLE. The association between raised IL-6 and worse current cognitive function in SLE should be explored in larger datasets.

Phosphorus flows in a peri-urban region with intensive food production: A case study.

Excess phosphorus (P) in peri-urban regions is an emerging issue, whereas there is global depletion of quality mined supplies of P. The flow of P across the landscape leading to regional surpluses and deficits is not well understood. We computed a regional P budget with internal P flows in a fairly discreet peri-urban region (Lower Fraser Valley, BC) with closely juxtaposed agricultural and non-agricultural urban ecosystems, in order to clarify the relationship between food production, food consumption and other activities involving use of P (e.g. keeping pets and horses and using soaps). We hypothesized changes that might notably improve P efficiency in peri-urban settings and wider regions. Livestock feed for the dairy and poultry sectors was the largest influx of P: the peri-urban land is too limited to grow feed grains and they are imported from outside the region. Fertilizer and import of food were the next largest influxes of P and a similar amount of P flows as food from the agricultural to urban ecosystems. Export of horticultural crops (berries and greenhouse crops) and poultry represented agricultural effluxes that partially offset the influxes. P efficiency was lower for horticultural production (21%) than animal production (32%), the latter benefited from importing feed crops, suggesting a regional advantage for animal products. There was 2.0, 3.8, 5.7 and 5.6 tonnes imported P per $ million farm cash receipts for horticulture, dairy, poultry meat and eggs. Eliminating fertilizer for corn and grass would reduce the ratio for the dairy industry. The net influx, dominated by fertilizer, animal feed and food was 8470 tonnes P per year or 3.2 kg P per person per year, and of this the addition to agricultural soils was 3650 tonnes P. The efflux in sewage effluent to the sea was 1150 tonnes P and exported sewage solids was 450 tonnes P. Municipal solid waste disposal was most difficult to quantify and was about 1800 tonnes P, 80% of which was partly reused in the urban regions and partly sequestered in landfill, which may be considered an efflux or a surplus. Reuse of rendering waste for feeding poultry significantly reduced P importation, but no rendering waste is used for cattle due to health concerns. Sensitivity analysis showed that variation in human population and the amount of P consumed per person in chicken and dairy products had the most influence on the total movement of P from agricultural to urban-ecosystems. There are current farm practices that mitigate P surpluses and new technologies are being developed to further reduce farm imbalances. However, current waste management policies that promote practices such composting of home wastes and exporting of poultry manure and biosolids to semiarid rangeland do little to enhance overall P cycling because the P is not returned to the farms producing feed and food for the peri-urban region. Sequestering in landfills may be a better solution until better ways are found to return surplus P.

The Prevalence of Grass Pollen-Related Allergic Rhinoconjunctivitis in Elite Amateur Irish Athletes.

Allergic rhinoconjunctivitis (AR/C), has been shown to impact upon athletic performance. The championships of the unique, amateur Irish sports of hurling and Gaelic football (collectively known as GAA) take place during the prime pollen months of summer. Elite GAA players must perform optimally when most exposed to pollen. Elite GAA subjects (n=254) underwent skin prick testing to 6 aeroallergens and completed a validated questionnaire (AQUA), producing a score indicating likelihood of having allergy. The prevalence of allergy (positive to at least one aeroallergen on SPT and positive AQUA score) was 27.1% (n=69). Sixteen and a half percent (n=42) of the subjects tested had grass pollen AR/C while 22% (n=54) had house dust mite AR/C, though none were on standard medical therapies or had used allergen-specific immunotherapy. Grass pollen AR/C prevalence appears as common in elite Irish athletes as it is in other countries. It appears to be mild rather than well controlled in these subjects.

Novel thogotovirus associated with febrile illness and death, United States, 2014.

A previously healthy man from eastern Kansas, USA, sought medical care in late spring because of a history of tick bite, fever, and fatigue. The patient had thrombocytopenia and leukopenia and was given doxycycline for a presumed tickborne illness. His condition did not improve. Multiorgan failure developed, and he died 11 days after illness onset from cardiopulmonary arrest. Molecular and serologic testing results for known tickborne pathogens were negative. However, testing of a specimen for antibodies against Heartland virus by using plaque reduction neutralization indicated the presence of another virus. Next-generation sequencing and phylogenetic analysis identified the virus as a novel member of the genus Thogotovirus.

Visual system evolution and the nature of the ancestral snake.

The dominant hypothesis for the evolutionary origin of snakes from 'lizards' (non-snake squamates) is that stem snakes acquired many snake features while passing through a profound burrowing (fossorial) phase. To investigate this, we examined the visual pigments and their encoding opsin genes in a range of squamate reptiles, focusing on fossorial lizards and snakes. We sequenced opsin transcripts isolated from retinal cDNA and used microspectrophotometry to measure directly the spectral absorbance of the photoreceptor visual pigments in a subset of samples. In snakes, but not lizards, dedicated fossoriality (as in Scolecophidia and the alethinophidian Anilius scytale) corresponds with loss of all visual opsins other than RH1 (λmax 490-497 nm); all other snakes (including less dedicated burrowers) also have functional sws1 and lws opsin genes. In contrast, the retinas of all lizards sampled, even highly fossorial amphisbaenians with reduced eyes, express functional lws, sws1, sws2 and rh1 genes, and most also express rh2 (i.e. they express all five of the visual opsin genes present in the ancestral vertebrate). Our evidence of visual pigment complements suggests that the visual system of stem snakes was partly reduced, with two (RH2 and SWS2) of the ancestral vertebrate visual pigments being eliminated, but that this did not extend to the extreme additional loss of SWS1 and LWS that subsequently occurred (probably independently) in highly fossorial extant scolecophidians and A. scytale. We therefore consider it unlikely that the ancestral snake was as fossorial as extant scolecophidians, whether or not the latter are para- or monophyletic.

Impact of rosiglitazone on body composition, hepatic fat, fatty acids, adipokines and glucose in persons with impaired fasting glucose or impaired glucose tolerance: a sub-study of the DREAM trial.

AIMS: Thiazolidinediones reduce ectopic fat, increase adiponectin and reduce inflammatory adipokines, fatty acids and glucose in people with Type 2 diabetes. We aimed to measure these effects in people with impaired fasting glucose and/or impaired glucose tolerance. METHODS: After approximately 3.5 years of exposure to rosiglitazone 8 mg (n = 88) or placebo (n = 102), 190 DREAM trial participants underwent abdominal computed tomography and dual-energy X-ray absorptiometry scans. Visceral and subcutaneous adipose tissue areas, estimated hepatic fat content, total fat and lean mass were calculated and changes in levels of fasting adipokines, free fatty acids, glucose and post-load glucose were assessed. RESULTS: Compared with the placebo, participants on rosiglitazone had no difference in lean mass, had 4.1 kg more body fat (P < 0.0001) and 31 cm(2) more subcutaneous abdominal adipose tissue area (P = 0.007). Only after adjusting for total fat, participants on rosiglitazone had 23 cm² less visceral adipose tissue area (P = 0.01) and an 0.08-unit higher liver:spleen attenuation ratio (i.e. less hepatic fat; P = 0.02) than those on the placebo. Adiponectin increased by 15.0 µg/ml with rosiglitazone and by 0.4 µg/ml with placebo (P < 0.0001). Rosiglitazone's effect on fat distribution was not independent of changes in adiponectin. Rosiglitazone's effects on fasting (-0.36 mmol/l; P = 0.0004) and 2-h post-load glucose (-1.21 mmol/l; P = 0.0008) were not affected by adjustment for fat distribution or changes in adiponectin or free fatty acids. CONCLUSIONS: In people with impaired fasting glucose/impaired glucose tolerance, rosiglitazone is associated with relatively less hepatic and visceral fat, increased subcutaneous fat and increased adiponectin levels. These effects do not appear to explain the glucose-lowering effect of rosiglitazone.

Outbreak of cryptosporidiosis among responders to a rollover of a truck carrying calves - Kansas, April 2013.

In April 2013, the Thomas County Health Department notified the Kansas Department of Health and Environment's Infectious Disease Epidemiology and Response section (KDHE) of two cases of cryptosporidiosis among emergency responders to a tractor-trailer rollover. The truck was carrying approximately 350 preweaned Holstein calves. An outbreak investigation was led by KDHE with assistance from the county health department; six cases of cryptosporidiosis were identified among the 15 emergency responders. No additional primary cases with this exposure or secondary cases were identified. Disease was associated with carrying calves (relative risk [RR] = 3.0) and contact with fecal matter (RR = 4.5). The calves were aged <10 days and reportedly suffered from scours (diarrheal disease), which is often caused by Cryptosporidium spp., a chlorine-tolerant protozoan parasite. Because of the age of the calves and the conditions at the rollover scene, a high potential existed for fecal contamination and subsequent transmission of Cryptosporidium. This outbreak is the first report of both law enforcement and volunteer emergency responders contracting cryptosporidiosis, with transmission of Cryptosporidium attributed solely to direct contact with animals and their feces. Human illness resulting from contact with animals during an emergency response might be minimized if 1) all responders are aware of the potential for zoonotic transmission, 2) education is provided on proper animal handling including the use of appropriate personal protective equipment, and 3) responders practice thorough hand hygiene and decontaminate clothing and equipment following contact with feces.

Does it run in the family? - Improving radiological risk assessment in the coastal environment using taxonomic and phylogenetic perspectives in macroalgae species.

Marine macroalgae are widely used indicator species for monitoring environmental radioactivity. Empirical studies have demonstrated a range in radionuclide transfer coefficients, or concentration ratios (CRs), between taxonomic groups, however the CR values used for dose estimation assume that macroalgae are a homogenous group, represented by a single CR. This study demonstrates the presence of a taxonomic signal in macroalgae CRs for multiple anthropogenic and naturally occurring radionuclides (137Cs, 241Am, 239+240Pu, 210Po) based on a collation of available data. A Residual Maximum Likelihood (REML) mixed model was applied, producing relative estimate CRs specific to each species within the datasets. The collated data was also analysed for a phylogenetic signal, but only a weak signal was found for one radionuclide in one group (239+240Pu in Phaeophyceae). A theoretical case study using the estimated CRs and the ERICA tool was carried out to demonstrate the implications of these findings in a real-world scenario.

Diagnosing and managing anorexia nervosa in UK primary care: a focus group study.

BACKGROUND: Anorexia is a leading cause of adolescent hospital admission and death from psychiatric disorder. Despite the potential role of general practitioners in diagnosis, appropriate referral and coordinating treatment, few existing studies provide fine-grained accounts of GPs' beliefs about anorexia. OBJECTIVES: To identify GPs' understandings and experiences of diagnosing and managing patients with anorexia in primary care. METHODS: Case-based focus groups with co-working general practitioners in the East Midlands region of England were used to explore attitudes towards issues common to patients with eating disorders. Group discussions were transcribed and analysed using corpus linguistic and discourse analytic approaches. RESULTS: Participants' discussion focused on related issues of making hesitant diagnoses, the utility of the body mass index, making referrals and overcoming patient resistance. Therapeutic relationships with patients with anorexia are considered highly complex, with participants using diagnostic tests as rhetorical strategies to help manage communicative obstacles. CONCLUSIONS: Overcoming patient repudiation and securing referrals are particular challenges with this patient group. Successfully negotiating these problems appears to require advanced communication skills.

Genetic linkage of cone-rod retinal dystrophy to chromosome 19q and evidence for segregation distortion.

Inherited retinal dystrophies are the most common cause of childhood blindness in the developed world. Cone-rod retinal dystrophies are severe examples of this group of disorders. Analysis of a large cone-rod dystrophy pedigree suggested that inheritance within the family was influenced by meiotic drive (p = 0.008), a rare segregation distortion in human genetics. Two-point linkage analysis showed significant linkage with three markers mapping to chromosome 19q. Multipoint analysis gave a maximum lod score of 10.08 (theta = 0.05) distal to D19S47. Cone-rod dystrophy is therefore assigned to 19q13.1-q13.2 and a new candidate locus for other retinal dystrophies is identified.

Restoration of photoreceptor ultrastructure and function in retinal degeneration slow mice by gene therapy.

The gene Prph2 encodes a photoreceptor-specific membrane glycoprotein, peripherin-2 (also known as peripherin/rds), which is inserted into the rims of photoreceptor outer segment discs in a complex with rom-1 (ref. 2). The complex is necessary for the stabilization of the discs, which are renewed constantly throughout life, and which contain the visual pigments necessary for photon capture. Mutations in Prph2 have been shown to result in a variety of photoreceptor dystrophies, including autosomal dominant retinitis pigmentosa and macular dystrophy. A common feature of these diseases is the loss of photoreceptor function, also seen in the retinal degeneration slow (rds or Prph2 Rd2/Rd2) mouse, which is homozygous for a null mutation in Prph2. It is characterized by a complete failure to develop photoreceptor discs and outer segments, downregulation of rhodopsin and apoptotic loss of photoreceptor cells. The electroretinograms (ERGs) of Prph2Rd2/Rd2 mice have greatly diminished a-wave and b-wave amplitudes, which decline to virtually undetectable concentrations by two months. Subretinal injection of recombinant adeno-associated virus (AAV) encoding a Prph2 transgene results in stable generation of outer segment structures and formation of new stacks of discs containing both perpherin-2 and rhodopsin, which in many cases are morphologically similar to normal outer segments. Moreover, the re-establishment of the structural integrity of the photoreceptor layer also results in electrophysiological correction. These studies demonstrate for the first time that a complex ultrastructural cell defect can be corrected both morphologically and functionally by in vivo gene transfer.