Discovery of a Ni2+-dependent guanidine hydrolase in bacteria.

Nitrogen availability is a growth-limiting factor in many habitats1, and the global nitrogen cycle involves prokaryotes and eukaryotes competing for this precious resource. Only some bacteria and archaea can fix elementary nitrogen; all other organisms depend on the assimilation of mineral or organic nitrogen. The nitrogen-rich compound guanidine occurs widely in nature2-4, but its utilization is impeded by pronounced resonance stabilization5, and enzymes catalysing hydrolysis of free guanidine have not been identified. Here we describe the arginase family protein GdmH (Sll1077) from Synechocystis sp. PCC 6803 as a Ni2+-dependent guanidine hydrolase. GdmH is highly specific for free guanidine. Its activity depends on two accessory proteins that load Ni2+ instead of the typical Mn2+ ions into the active site. Crystal structures of GdmH show coordination of the dinuclear metal cluster in a geometry typical for arginase family enzymes and allow modelling of the bound substrate. A unique amino-terminal extension and a tryptophan residue narrow the substrate-binding pocket and identify homologous proteins in further cyanobacteria, several other bacterial taxa and heterokont algae as probable guanidine hydrolases. This broad distribution suggests notable ecological relevance of guanidine hydrolysis in aquatic habitats.

Development and preliminary evaluation of the Neurofibromatosis Type 1 Adult Quality of Life (NF1-AdQoL) questionnaire.

BACKGROUND: Neurofibromatosis Type 1 (NF1) is a variable and unpredictable multisystem genetic disorder that predisposes to medical complications, cognitive impairment and disfigurement, of all which can impact negatively upon the health-related quality of life (HRQoL) of affected adults. AIMS: To develop and validate a disease-specific HRQoL adult questionnaire to evaluate effects of NF1 from the patient's viewpoint. METHODS: The Neurofibromatosis Type 1 Adult Health-related Quality of Life questionnaire (NF1-AdQoL) was based on patient interviews (n = 8), clinician survey and questionnaire pilot study. Adults with NF1 (n = 114, aged 18-40 years) were recruited from three Australian genetics clinics and completed the NF1-AdQoL, the 29-item Skindex (Skindex-29) and the 36-item Short Form, version 2 (SF-36v2) questionnaires. An exploratory factor analysis of the NF1-AdQoL was conducted to assess construct validity. Convergent and discriminant validity of the NF1-AdQoL was determined by using multitrait multimethod analysis with Skindex-29 and SF-36v2 scores. RESULTS: Factor analysis indicated that 62.7% of the common variance between the questionnaires could be explained by three factors: 'emotions associated with cosmetic appearance' (12 items), 'functioning - social and learning' (11 items) and 'physical symptoms' (8 items). NF1-AdQoL had good internal consistency (Cronbach α = 0.96). Convergent validity was confirmed by moderate associations with similarly named scales of the Skindex-29 and SF-36v2. Results from all three HRQoL questionnaires indicated overall healthy HRQoL for young to early middle-aged adults with NF1. CONCLUSION: The NF1-AdQoL is a relatively valid, feasible and fairly easy to read tool to measure the HRQoL of adults with NF1. Further evaluation is required to determine the test-retest reliability, responsiveness and validity of the NF1-AdQoL in larger adult NF1 cohorts.

Case Report: Congenital Methaemoglobinaemia Type 1: Benign Cyanosis?

Type 1 congenital methaemoglobinaemia is a rare cause of cyanosis which may manifest in affected individuals during concomitant illness. Treatment indications and aims differ from that of acquired methaemoglobinaemia. Type 1 methaemoglobinaemia is a distinct condition from the type 2 form which has a high mortality rate in infancy. A 25 year old male with known type 1 congential methaemoglobinaemia presented with cyanosis in the context of Influenza A with raised methaemoglobin levels on arterial blood gas analysis. The patient was assessed based on his level of 'functional haemoglobin' with no acute indication for IV methylene blue or ascorbic acid. Consideration could be given to prescription of these on a cosmetic basis for some patient populations.

Bioengineered human skeletal muscle capable of functional regeneration.

BACKGROUND: Skeletal muscle (SkM) regenerates following injury, replacing damaged tissue with high fidelity. However, in serious injuries, non-regenerative defects leave patients with loss of function, increased re-injury risk and often chronic pain. Progress in treating these non-regenerative defects has been slow, with advances only occurring where a comprehensive understanding of regeneration has been gained. Tissue engineering has allowed the development of bioengineered models of SkM which regenerate following injury to support research in regenerative physiology. To date, however, no studies have utilised human myogenic precursor cells (hMPCs) to closely mimic functional human regenerative physiology. RESULTS: Here we address some of the difficulties associated with cell number and hMPC mitogenicity using magnetic association cell sorting (MACS), for the marker CD56, and media supplementation with fibroblast growth factor 2 (FGF-2) and B-27 supplement. Cell sorting allowed extended expansion of myogenic cells and supplementation was shown to improve myogenesis within engineered tissues and force generation at maturity. In addition, these engineered human SkM regenerated following barium chloride (BaCl2) injury. Following injury, reductions in function (87.5%) and myotube number (33.3%) were observed, followed by a proliferative phase with increased MyoD+ cells and a subsequent recovery of function and myotube number. An expansion of the Pax7+ cell population was observed across recovery suggesting an ability to generate Pax7+ cells within the tissue, similar to the self-renewal of satellite cells seen in vivo. CONCLUSIONS: This work outlines an engineered human SkM capable of functional regeneration following injury, built upon an open source system adding to the pre-clinical testing toolbox to improve the understanding of basic regenerative physiology.

Orbital exenteration and reconstruction in a tertiary UK institution: a 5-year experience.

PURPOSE: Orbital exenteration is a radical oncological surgery that is usually indicated for advanced primary orbital tumors or invasion from local malignancy. We report a 5-year series from a tertiary head and neck center with particular focus on our ablative and reconstructive approach. METHODS: We performed a clinicopathological review of patients referred to Guy's and St Thomas' NHS Foundation Trust Head and Neck multidisciplinary team for management input of an orbital malignancy during the period of 2013 to 2018. Cases involving local invasion from sinonasal malignancy were excluded. The reconstructive approach, perioperative complications, disease-free and overall survival were analyzed. RESULTS: 27 patients were identified and of those treated surgically, a radical extended orbital exenteration was required in almost half (44.4%), with squamous cell carcinoma being the most common pathology (55.6%). A concurrent neck dissection and parotidectomy were commonly performed with confirmed or suspected regional disease, or in the presence of high-risk pathological features. This approach resulted in favourable 2-year overall survival in these advanced stage cases of 84.6% and disease-free survival of 73.2%, with 92% achieving a negative surgical margin. The majority of treated patients required a free flap reconstruction, especially when an extended exenteration defect or adjuvant treatment was anticipated. The anterolateral thigh flap was the most commonly used donor site, and we present our algorithm for reconstruction of these defects. CONCLUSIONS: A multidisciplinary approach to advanced orbital malignancy with a comprehensive approach to surgical resection and reconstruction results in favorable oncological outcomes and addresses functional and cosmetic patient rehabilitation.

Variation of the minimally invasive CDCR technique.

Purpose: Traditional (tCDCR) and endoscopic conjunctivodacryocystorhinostomy (eCDCR) are challenging surgical techniques requiring general anesthesia, a facial incision, and a large osteotomy and mucosal flap. Minimally invasive CDCR (miCDCR) techniques eliminate the need for some of the steps in t/eCDCR. Introduced here is a variation of the miCDCR technique using a Naugle-Fleming knurled dilator (NKD) to create the osteotomy and instruments within a central line catheter kit to help easily place or replace a Jones' tube into position within a bony conduit.Methods: This IRB-approved retrospective chart review examined all patients who underwent this miCDCR technique performed by two oculoplastic surgeons at Hamilton Eye Institute at the University of Tennessee Health Sciences Center from 2014 to 2016. Inclusion criteria: need for CDCR (either primary or repeat). Exclusion criteria: loss to follow up prior to six months. Primary endpoints: operative time, incidence of tube migration and complications, and cessation of epiphora.Results: Sixteen patients (nine men, seven women) were reviewed, with three undergoing bilateral procedure, totaling 19 cases. Age range: 47.0 to 84.0 years, average of 66.6 years (SD = 11.1). Ten patients had surgery under local/MAC augmented with IV sedation, and six had general anesthesia (38%). Average operative time was 17.4 min (SD = 10.9). One patient (5%) required revision in the six-month immediate post-operative period because of tube migration. All patients had cessation of epiphora.Conclusions: This procedure can be done safely and quickly without general anesthesia, resulting in a satisfactorily lower rate of tube migration and cessation of epiphora rates.

The effect of Share 35 on biliary complications: An interrupted time series analysis.

The purpose of the Share 35 allocation policy was to improve liver transplant waitlist mortality, targeting high MELD waitlisted patients. However, policy changes may also have unintended consequences that must be balanced with the primary desired outcome. We performed an interrupted time series assessing the impact of Share 35 on biliary complications in a select national liver transplant population using the Vizient CDB/RM database. Liver transplants that occurred between October 2012 and September 2015 were included. There was a significant change in the incident-rate of biliary complications between Pre-Share 35 (n = 3018) and Post-Share 35 (n = 9984) cohorts over time (P = .023, r2  = .44). As a control, a subanalysis was performed throughout the same time period in Region 9 transplant centers, where a broad sharing agreement had previously been implemented. In the subanalysis, there was no change in the incident-rate of biliary complications between the two time periods. Length of stay and mean direct cost demonstrated a change after implementation of Share 35, although they did not meet statistical difference. While the target of improved waitlist mortality is of utmost importance for the equitable allocation of organs, unintended consequences of policy changes should be studied for a full assessment of a policy's impact.

Enhancement of gemcitabine cytotoxicity in pancreatic adenocarcinoma through controlled release of nitric oxide.

Gemcitabine (GEM) is the first-line treatment for pancreatic adenocarcinoma (PAC) yet chemoresistance is common. Nitric oxide (NO) is the predominant species responsible for the cytotoxic action of macrophages against cancer cells yet localized delivery is difficult given the short half-life. We sought to study the effect of locally delivered NO on GEM mediated PAC cytotoxicity and the potential role of SMAD4 in this effect. We hypothesized that NO would enhance the cytotoxicity of GEM in a SMAD4 dependent manner. NO-Silica nanoparticles (NO-Si) were synthesized via a co-condensation of tetraethoxysilane with aminoalkoxysilane under high-pressure nitrous oxide. NO release was measured using chemiluminescence. A SMAD4 negative PAC cell line (SMAD4-) was made using retroviral knockdown of Panc1 PAC cells. Panc1 and SMAD4- cells were treated with gemcitabine (100 nm (hi) to 30 µm (lo)), 30 mg NOSi particles, or both (NOSihi or NOSilo) and cell viability assessed. NoSi reduced cell viability by 25.99% in Panc1 and 24.38% in SMAD4-. When combined with gemcitabine, further reductions were seen in a dose dependent manner for both cell lines. We have demonstrated the in-vitro dose dependent cytotoxic effects of NOSi. When combined with GEM there is a synergistic effect resulting in improved cytotoxicity seen in both Panc1 and SMAD4- PAC cells with a differential pattern of cell death seen at high concentrations of NO. These findings suggest not only that NO is useful chemosensitizing agent but that SMAD4- may play a role in its synergism with GEM.

Mobile Health in Solid Organ Transplant: The Time Is Now.

Despite being in existence for >40 years, the application of telemedicine has lagged significantly in comparison to its generated interest. Detractors include the immobile design of most historic telemedicine interventions and the relative lack of smartphones among the general populace. Recently, the exponential increase in smartphone ownership and familiarity have provided the potential for the development of mobile health (mHealth) interventions that can be mirrored realistically in clinical applications. Existing studies have demonstrated some potential clinical benefits of mHealth in the various phases of solid organ transplantation (SOT). Furthermore, studies in nontransplant chronic diseases may be used to guide future studies in SOT. Nevertheless, substantially more must be accomplished before mHealth becomes mainstream. Further evidence of clinical benefits and a critical need for cost-effectiveness analysis must prove its utility to patients, clinicians, hospitals, insurers, and the federal government. The SOT population is an ideal one in which to demonstrate the benefits of mHealth. In this review, the current evidence and status of mHealth in SOT is discussed, and a general path forward is presented that will allow buy-in from the health care community, insurers, and the federal government to move mHealth from research to standard care.

Beam-Target Helicity Asymmetry for γ[over →]n[over →]→π

We report the first beam-target double-polarization asymmetries in the γ+n(p)→π^{-}+p(p) reaction spanning the nucleon resonance region from invariant mass W=1500 to 2300 MeV. Circularly polarized photons and longitudinally polarized deuterons in solid hydrogen deuteride (HD) have been used with the CEBAF Large Acceptance Spectrometer (CLAS) at Jefferson Lab. The exclusive final state has been extracted using three very different analyses that show excellent agreement, and these have been used to deduce the E polarization observable for an effective neutron target. These results have been incorporated into new partial wave analyses and have led to significant revisions for several γnN^{*} resonance photocouplings.

A composite smeared finite element for mass transport in capillary systems and biological tissue.

One of the key processes in living organisms is mass transport occurring from blood vessels to tissues for supplying tissues with oxygen, nutrients, drugs, immune cells, and - in the reverse direction - transport of waste products of cell metabolism to blood vessels. The mass exchange from blood vessels to tissue and vice versa occurs through blood vessel walls. This vital process has been investigated experimentally over centuries, and also in the last decades by the use of computational methods. Due to geometrical and functional complexity and heterogeneity of capillary systems, it is however not feasible to model in silico individual capillaries (including transport through the walls and coupling to tissue) within whole organ models. Hence, there is a need for simplified and robust computational models that address mass transport in capillary-tissue systems. We here introduce a smeared modeling concept for gradient-driven mass transport and formulate a new composite smeared finite element (CSFE). The transport from capillary system is first smeared to continuous mass sources within tissue, under the assumption of uniform concentration within capillaries. Here, the fundamental relation between capillary surface area and volumetric fraction is derived as the basis for modeling transport through capillary walls. Further, we formulate the CSFE which relies on the transformation of the one-dimensional (1D) constitutive relations (for transport within capillaries) into the continuum form expressed by Darcy's and diffusion tensors. The introduced CSFE is composed of two volumetric parts - capillary and tissue domains, and has four nodal degrees of freedom (DOF): pressure and concentration for each of the two domains. The domains are coupled by connectivity elements at each node. The fictitious connectivity elements take into account the surface area of capillary walls which belongs to each node, as well as the wall material properties (permeability and partitioning). The overall FE model contains geometrical and material characteristics of the entire capillary-tissue system, with physiologically measurable parameters assigned to each FE node within the model. The smeared concept is implemented into our implicit-iterative FE scheme and into FE package PAK. The first three examples illustrate accuracy of the CSFE element, while the liver and pancreas models demonstrate robustness of the introduced methodology and its applicability to real physiological conditions.

Total Laparoscopic Central Pancreatectomy with Pancreaticogastrostomy for High-Risk Cystic Neoplasm.

BACKGROUND: Organ-sparing pancreatic resection is important in prophylactic surgery for cystic neoplasms. There is controversy regarding the optimal surgical approach for pancreatic lesions in the neck or proximal body of the pancreas. Central compared with distal pancreatectomy is technically more challenging, but preserves more functional pancreatic tissue. Because of the prophylactic nature of the surgery and long survival of patients with benign and borderline malignant lesions, surgeons need to stratify greater importance to surgical morbidity and sparing pancreatic parenchyma. PATIENT: The patient is a 59-year-old active woman with a symptomatic cystic neoplasm of the pancreas exhibiting high-risk imaging features. The cyst of 2.2 × 1.8 cm in the body of the pancreas was impinging on the portal venous confluence. TECHNIQUE: The patient was positioned in the French Position, the lesser sac was opened, and the pancreatic body exposed. A retropancreatic tunnel was created with staple division of the neck. The body was mobilized off the portal vein and splenic vessels transected. A retrogastric pancreaticogastrostomy was sewn through an anterior gastrotomy. The stent was delivered past the pylorus to decrease pancreatic enzymatic activation. Pathology demonstrated a mixed predominantly branch duct IPMN with multifocal high grade dysplasia and PanIN3. CONCLUSIONS: Laparoscopic ultrasound helps in defining cyst borders, and minimal blood loss optimizes visualization during the dissection. A minimally invasive pancreaticogastrostomy created through an anterior gastrotomy is technically feasible and safe. This approach can minimize the morbidity of prophylactic pancreatic surgery for patients with cystic neoplasms. Nevertheless, it should not compromise safety, oncologic completeness, or an organ-sparing approach.

Cross Sections for the Exclusive Photon Electroproduction on the Proton and Generalized Parton Distributions.

Unpolarized and beam-polarized fourfold cross sections (d^{4}σ/dQ^{2}dx_{B}dtdϕ) for the ep→e^{'}p^{'}γ reaction were measured using the CLAS detector and the 5.75-GeV polarized electron beam of the Jefferson Lab accelerator, for 110 (Q^{2},x_{B},t) bins over the widest phase space ever explored in the valence-quark region. Several models of generalized parton distributions (GPDs) describe the data well at most of our kinematics. This increases our confidence that we understand the GPD H, expected to be the dominant contributor to these observables. Through a leading-twist extraction of Compton form factors, these results support the model predictions of a larger nucleon size at lower quark-momentum fraction x_{B}.

Towards a resolution of the proton form factor problem: new electron and positron scattering data.

There is a significant discrepancy between the values of the proton electric form factor, G(E)(p), extracted using unpolarized and polarized electron scattering. Calculations predict that small two-photon exchange (TPE) contributions can significantly affect the extraction of G(E)(p) from the unpolarized electron-proton cross sections. We determined the TPE contribution by measuring the ratio of positron-proton to electron-proton elastic scattering cross sections using a simultaneous, tertiary electron-positron beam incident on a liquid hydrogen target and detecting the scattered particles in the Jefferson Lab CLAS detector. This novel technique allowed us to cover a wide range in virtual photon polarization (ϵ) and momentum transfer (Q(2)) simultaneously, as well as to cancel luminosity-related systematic errors. The cross section ratio increases with decreasing ϵ at Q(2)=1.45 GeV(2). This measurement is consistent with the size of the form factor discrepancy at Q(2)≈1.75 GeV(2) and with hadronic calculations including nucleon and Δ intermediate states, which have been shown to resolve the discrepancy up to 2-3 GeV(2).

Longitudinal target-spin asymmetries for deeply virtual compton scattering.

A measurement of the electroproduction of photons off protons in the deeply inelastic regime was performed at Jefferson Lab using a nearly 6 GeV electron beam, a longitudinally polarized proton target, and the CEBAF Large Acceptance Spectrometer. Target-spin asymmetries for ep→e^{'}p^{'}γ events, which arise from the interference of the deeply virtual Compton scattering and the Bethe-Heitler processes, were extracted over the widest kinematics in Q^{2}, x_{B}, t, and ϕ, for 166 four-dimensional bins. In the framework of generalized parton distributions, at leading twist the t dependence of these asymmetries provides insight into the spatial distribution of the axial charge of the proton, which appears to be concentrated in its center. These results also bring important and necessary constraints for the existing parametrizations of chiral-even generalized parton distributions.

Clinical trials of helminth therapy in autoimmune diseases: rationale and findings.

Some helminths are major human pathogens. Recently, however, increased understanding of the immunoregulatory responses induced by this class of parasites, in combination with epidemiologic and animal studies, suggests that helminths may have therapeutic potential in autoimmune diseases (AD) and other conditions. This article reviews the rationale for and results of clinical trials to test the safety and efficacy of helminth therapy in AD. Also discussed are future prospects for investigation and the possibility that helminth treatment may serve as a probe to help reveal the pathogenesis of AD.

Prediction of medication non-adherence and associated outcomes in pediatric kidney transplant recipients.

Studies have continued to evaluate risk factors associated with post-transplant non-adherence in pediatric patients. However, many of these studies fail to evaluate how risk factors can be utilized to predict MNA. The aims of this study were to (i) determine salient risk factors associated with MNA to develop an adequate predictive risk model and (ii) assess transplant outcomes based on the presence of MNA in a large, diverse cohort of pediatric KTX recipients. One hundred and seventy-five solitary pediatric KTX recipients transplanted from 1999 to 2013 were included. AA, males, older patients, those who lived in urban environments, had legal issues, and lived shorter distances from the transplant center were more likely to have MNA. Using logistic regression, a parsimonious model applying nine risk factors together was developed for predicting MNA, demonstrating a PPV of 69% and a NPV of 81%. Patients with MNA had more than twice the risk of biopsy proven acute rejection, 1.6 times the risk of hospitalization, and 1.8 times the risk of graft loss. Utilization of a predictive model to determine risk of MNA after pediatric KTX may offer clinicians the ability to efficiently and effectively monitor MNA following transplant.

Docosahexaenoic acid-enriched canola oil increases adiponectin concentrations: a randomized crossover controlled intervention trial.

BACKGROUND AND AIMS: Little is known about the effect of various dietary fatty acids on pro- and anti-inflammatory processes. We investigated the effect of 5 oils containing various amounts of alpha-linolenic acid (ALA), linoleic acid (LA), oleic acid (OA) and docosahexaenoic acid (DHA) on plasma inflammatory biomarkers and expression levels of key inflammatory genes and transcription factors in whole blood cells. METHODS AND RESULTS: In a randomized, crossover controlled nutrition intervention, 114 adult men and women with abdominal obesity and at least one other criterion for the metabolic syndrome consumed 5 experimental isoenergetic diets for 4 weeks each, separated by 4-week washout periods. Each diet provided 60 g/3000 kcal of different oils: 1) control corn/safflower oil blend (CornSaff; LA-rich), 2) flax/safflower oil blend (FlaxSaff; ALA-rich), 3) conventional canola oil (Canola; OA-rich), 4) high oleic canola oil (CanolaOleic; highest OA content), 5) DHA-enriched high oleic canola oil (CanolaDHA; OA- and DHA-rich). Gene expression in whole blood cells was assessed in a subset of 62 subjects. CanolaDHA increased plasma adiponectin concentrations compared with the control CornSaff oil treatment (+4.5%, P = 0.04) and FlaxSaff (+6.9%, P = 0.0008). CanolaDHA also reduced relative expression levels of interleukin (IL)1B compared with CornSaff and Canola (-11% and -13%, respectively, both P = 0.03). High-sensitivity C-reactive protein concentrations were lower after Canola than after FlaxSaff (-17.8%, P = 0.047). CONCLUSION: DHA-enriched canola oil exerts anti-inflammatory effects compared with polyunsaturated fatty acids from plant sources.

Attitudes of the general public towards the disclosure of individual research results and incidental findings from biobank genomic research in Australia.

BACKGROUND: Over the past decade, managing the disclosure of findings of genomic research has been the subject of extensive scientific, ethical and legal commentary and is a major challenge for biobanks. AIMS: To examine views of the general Australian public about the disclosure of individual research results (IRR) and incidental findings (IF) from biobank genomic research. METHODS: A national computer assisted telephone interview was conducted amongst a representative sample of (n = 800) adult residents across each Australian State and Territory. RESULTS: The majority of the Australian general public would be interested in receiving IRR and IF if they allowed their blood/tissue to be used in research; 94.4% (n = 800) reported that they would like to receive 'specific information obtained from your sample that may be important to your health or treatment', and 83.4% their 'potential genetic risk of an inherited disease'. Although fewer desired to receive 'any IF that were not directly related to your (potential) diagnosed condition' (70.0%), most would still like to receive IF. A latent class analysis on the desire to receive (or not) all types of results revealed differences in preferences in the information they wished to receive. CONCLUSION: The majority of Australians desire to receive most information arising from research involving their tissue, including IRR and IF. Differences in the extent and type of information they desire to receive are noted. Biobanks must establish strategies to identify information needs of donors, assess research data and communicate with donors and donor families. Processes need to take account of differences in donor preferences and in the clinical or research context(s).

Effective communication between ENT and primary care - a survey of outpatient correspondence.

OBJECTIVE: To improve the quality of outpatient clinic communication between Otolaryngology and primary care doctors. DESIGN: Three example outpatient letters with identical content were created using different structure styles - full prose, headline subheadings with full prose and full subheadings throughout. Electronic questionnaires were sent out to 30 randomly selected General Practitioners in the area served by Western Sussex NHS Trust. The electronic mail study invite contained the initial GP referral, the three different letter formats and a link to the Sheffield Assessment for Letters (SAIL) questionnaire, which contained a 18-point checklist, 6 rating subheadings with a 10-point rating scale and a free text comment section. Study participants were asked to read the letters in the time usually afforded to outpatient letters in their routine practice, answer questions and then rate the letters. RESULTS: With a response rate of 66.7%, overall comparison of GP preferences demonstrated a significant variation between the three letter formats (Freidman P value = 0.0001). Post hoc multiple comparisons showed statistically significant preference for the headline subheading and prose letter compared to the full subheaded letter (P < 0.05). In assessing the letters for readability, comprehension, usefulness, informativeness and helpfulness, analysis showed significant preference for both fully subheaded and headline subheaded with full prose structures compared to the full prose letter. CONCLUSION: Although the headline subheadings and prose letter had the highest word count, it scored the highest in almost all the rating categories analysed. This study is the first published work to study primary care physician's preference for the structure of letters from secondary care. Prominent headline subheadings of diagnosis and management improve interpretation of content and comprehension and are helpful to GPs for co-ordinating patient management. Lack of subheadings or conversely an excess of subheadings may be a hindrance to effective communication between healthcare professionals.