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Baculovirus is the most studied insect virus owing to a broad ecological distribution and ease of engineering for biotechnological applications. However, its structure and evolutionary place in the virosphere remain enigmatic. Using cryo-electron microscopy, we show that the nucleocapsid forms a covalently cross-linked helical tube protecting a highly compacted 134-kilobase pair DNA genome. The ends of the tube are sealed by the base and cap substructures, which share a 126-subunit hub but differ in components that promote actin tail-mediated propulsion and nuclear entry of the nucleocapsid, respectively. Unexpectedly, sensitive searches for hidden evolutionary links show that the morphogenetic machinery and conserved oral infectivity factors originated within the lineage of baculo-like viruses (class Naldaviricetes ). The unique viral architecture and structural atlas of hallmark proteins firmly place these viruses into a separate new realm, the highest taxonomy rank, and provide a structural framework to expand their use as sustainable bioinsecticides and biomedical tools.

Thrombopoietin (Tpo) is the primary regulator of megakaryocyte and platelet numbers and is required for haematopoetic stem cell maintenance. Tpo functions by binding its receptor (TpoR, a homodimeric Class I cytokine receptor) and initiating cell proliferation or differentiation. Here we characterise the murine Tpo:TpoR signalling complex biochemically and structurally, using cryo-electron microscopy. Tpo uses opposing surfaces to recruit two copies of receptor, forming a 1:2 complex. Although it binds to the same, membrane-distal site on both receptor chains, it does so with significantly different affinities and its highly glycosylated C-terminal domain is not required. In one receptor chain, a large insertion, unique to TpoR, forms a partially structured loop that contacts cytokine. Tpo binding induces the juxtaposition of the two receptor chains adjacent to the cell membrane. The therapeutic agent romiplostim also targets the cytokine-binding site and the characterisation presented here supports the future development of improved TpoR agonists., (© 2024. The Author(s).)

PEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. Despite lacking catalytic activity, alteration in their expression level is associated with several aggressive cancers. Here, we elucidate the molecular details of key PEAK signaling interactions with the adapter proteins CrkII and Grb2 and the scaffold protein 14-3-3. Our findings rationalize why the dimerization of PEAK proteins has a crucial function in signal transduction and provide biophysical and structural data to unravel binding specificity within the PEAK interactome. We identify a conserved high affinity 14-3-3 motif on PEAK3 and demonstrate its role as a molecular switch to regulate CrkII binding and signaling via Grb2. Together, our studies provide a detailed structural snapshot of PEAK interaction networks and further elucidate how PEAK proteins, especially PEAK3, act as dynamic scaffolds that exploit adapter proteins to control signal transduction in cell growth/motility and cancer., (© 2023. The Author(s).)

Doublecortin-like kinase 1 (DCLK1) is a functional serine/threonine (S/T)-kinase and a member of the doublecortin family of proteins which are characterized by their ability to bind to microtubules (MTs). DCLK1 is a proposed cancer driver gene, and its upregulation is associated with poor overall survival in several solid cancer types. However, how DCLK1 associates with MTs and how its kinase function contributes to pro-tumorigenic processes is poorly understood. This review builds on structural models to propose not only the specific functions of the domains but also attempts to predict the impact of individual somatic missense mutations on DCLK1 functions. Somatic missense mutations in DCLK1 are most frequently located within the N-terminal MT binding region and likely impact on the ability of DCLK1 to bind to αβ-tubulin and to polymerize and stabilize MTs. Moreover, the MT binding affinity of DCLK1 is negatively regulated by its auto-phosphorylation, and therefore mutations that affect kinase activity are predicted to indirectly alter MT dynamics. The emerging picture portrays DCLK1 as an MT-associated protein whose interactions with tubulin heterodimers and MTs are tightly controlled processes which, when disrupted, may confer pro-tumorigenic properties.

A vaccine to prevent hepatitis C virus (HCV) infection is urgently needed for use alongside direct-acting antiviral drugs to achieve elimination targets. We have previously shown that a soluble recombinant form of the glycoprotein E2 ectodomain (residues 384 to 661) that lacks three variable regions (Δ123) is able to elicit a higher titer of broadly neutralizing antibodies (bNAbs) than the parental form (receptor-binding domain [RBD]). In this study, we engineered a viral nanoparticle that displays HCV glycoprotein E2 on a duck hepatitis B virus (DHBV) small surface antigen (S) scaffold. Four variants of E2-S virus-like particles (VLPs) were constructed: Δ123-S, RBD-S, Δ123A7-S, and RBDA7-S; in the last two, 7 cysteines were replaced with alanines. While all four E2-S variant VLPs display E2 as a surface antigen, the Δ123A7-S and RBDA7-S VLPs were the most efficiently secreted from transfected mammalian cells and displayed epitopes recognized by cross-genotype broadly neutralizing monoclonal antibodies (bNMAbs). Both Δ123A7-S and RBDA7-S VLPs were immunogenic in guinea pigs, generating high titers of antibodies reactive to native E2 and able to prevent the interaction between E2 and the cellular receptor CD81. Four out of eight animals immunized with Δ123A7-S elicited neutralizing antibodies (NAbs), with three of those animals generating bNAbs against 7 genotypes. Immune serum generated by animals with NAbs mapped to major neutralization epitopes located at residues 412 to 420 (epitope I) and antigenic region 3. VLPs that display E2 glycoproteins represent a promising vaccine platform for HCV and could be adapted to large-scale manufacturing in yeast systems. IMPORTANCE There is currently no vaccine to prevent hepatitis C virus infection, which affects more than 71 million people globally and is a leading cause of progressive liver disease, including cirrhosis and cancer. Broadly neutralizing antibodies that recognize the E2 envelope glycoprotein can protect against heterologous viral infection and correlate with viral clearance in humans. However, broadly neutralizing antibodies are difficult to generate due to conformational flexibility of the E2 protein and epitope occlusion. Here, we show that a VLP vaccine using the duck hepatitis B virus S antigen fused to HCV glycoprotein E2 assembles into virus-like particles that display epitopes recognized by broadly neutralizing antibodies and elicit such antibodies in guinea pigs. This platform represents a novel HCV vaccine candidate amenable to large-scale manufacture at low cost.

The majority of phages, viruses that infect prokaryotes, inject their genomic material into their host through a tubular assembly known as a tail. Despite the genomic diversity of tailed phages, only three morphological archetypes have been described: contractile tails of Myoviridae-like phages; short non-contractile tails of Podoviridae-like phages; and long and flexible non-contractile tails of Siphoviridae-like phages. While early cryo-electron microscopy (cryo-EM) work elucidated the organisation of the syringe-like injection mechanism of contractile tails, the intrinsic flexibility of the long non-contractile tails prevented high-resolution structural determination. In 2020, four cryo-EM structures of Siphoviridae-like tail tubes were solved and revealed common themes and divergences. The central tube is structurally conserved and homologous to the hexameric rings of the tail tube protein (TTP) also found in contractile tails, bacterial pyocins, and type VI secretion systems. The interior surface of the tube presents analogous motifs of negatively charged amino acids proposed to facilitate ratcheting of the DNA during genome ejection. The lack of a conformational change upon genome ejection implicates the tape measure protein in triggering genome release. A distinctive feature of Siphoviridae-like tails is their flexibility. This results from loose inter-ring connections that can asymmetrically stretch on one side to allow bending and flexing of the tube without breaking. The outer surface of the tube differs greatly and may be smooth or rugged due to additional Ig-like domains in TTP. Some of these variable domains may contribute to adsorption of the phage to prokaryotic and eukaryotic cell surfaces affecting tropism and virulence., (© 2022 The Author(s).)

The PEAK family of pseudokinases, which comprises PEAK1, PEAK2 and PEAK3, are newly identified scaffolds that dynamically assemble oncogenic signaling pathways known to contribute to the development of several aggressive cancers. A striking feature of this unique family of pseudokinase scaffolds is their large multi-domain structure, which allows them to achieve protein complex assemblies through their structural plasticity and functional versatility. Recent structural advances have begun to reveal the critical regulatory elements that control their function. Specifically, the dimer-dependent scaffolding activity of PEAK pseudokinases is emerging as a critical mechanism for their signaling function, in addition to their ability to hetero-associate to form higher-order regulatory networks to diversify and amplify their signaling output. Here, we present a suite of techniques that enable the efficient expression and purification of PEAK proteins for functional characterization., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Doublecortin-like kinase 1 (DCLK1) is an understudied bi-functional kinase with a proven role in tumour growth and development. However, the presence of tissue-specific spliced DCLK1 isoforms with distinct biological functions have challenged the development of effective strategies to understand the role of DCLK1 in oncogenesis. Recently, DCLK1-IN-1 was reported as a highly selective DCLK1 inhibitor, a powerful tool to dissect DCLK1 biological functions. Here, we report the crystal structures of DCLK1 kinase domain in complex with DCLK1-IN-1 and its precursors. Combined, our data rationalises the structure-activity relationship that informed the development of DCLK1-IN-1 and provides the basis for the high selectivity of DCLK1-IN-1, with DCLK1-IN-1 inducing a drastic conformational change of the ATP binding site. We demonstrate that DCLK1-IN-1 binds DCLK1 long isoforms but does not prevent DCLK1's Microtubule-Associated Protein (MAP) function. Together, our work provides an invaluable structural platform to further the design of isoform-specific DCLK1 modulators for therapeutic intervention., (© 2021. The Author(s).)

The current COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We demonstrate that despite the large size of the viral RNA genome (~30 kb), infectious full-length cDNA is readily assembled in vitro by a circular polymerase extension reaction (CPER) methodology without the need for technically demanding intermediate steps. Overlapping cDNA fragments are generated from viral RNA and assembled together with a linker fragment containing CMV promoter into a circular full-length viral cDNA in a single reaction. Transfection of the circular cDNA into mammalian cells results in the recovery of infectious SARS-CoV-2 virus that exhibits properties comparable to the parental virus in vitro and in vivo. CPER is also used to generate insect-specific Casuarina virus with ~20 kb genome and the human pathogens Ross River virus (Alphavirus) and Norovirus (Calicivirus), with the latter from a clinical sample. Additionally, reporter and mutant viruses are generated and employed to study virus replication and virus-receptor interactions.

The epidemic emergence of relatively rare and geographically isolated flaviviruses adds to the ongoing disease burden of viruses such as dengue. Structural analysis is key to understand and combat these pathogens. Here, we present a chimeric platform based on an insect-specific flavivirus for the safe and rapid structural analysis of pathogenic viruses. We use this approach to resolve the architecture of two neurotropic viruses and a structure of dengue virus at 2.5  Å, the highest resolution for an enveloped virion. These reconstructions allow improved modelling of the stem region of the envelope protein, revealing two lipid-like ligands within highly conserved pockets. We show that these sites are essential for viral growth and important for viral maturation. These findings define a hallmark of flavivirus virions and a potential target for broad-spectrum antivirals and vaccine design. We anticipate the chimeric platform to be widely applicable for investigating flavivirus biology.

Flaviviruses are the cause of severe human diseases transmitted by mosquitoes and ticks. These viruses use a potent fusion machinery to enter target cells that needs to be restrained during viral assembly and egress. A molecular chaperone, premembrane (prM) maintains the virus particles in an immature, fusion-incompetent state until they exit the cell. Taking advantage of an insect virus that produces particles that are both immature and infectious, we determined the structure of the first immature flavivirus with a complete spike by cryo-electron microscopy. Unexpectedly, the prM chaperone forms a supporting pillar that maintains the immature spike in an asymmetric and upright state, primed for large rearrangements upon acidification. The collapse of the spike along a path defined by the prM chaperone is required, and its inhibition by a multivalent immunoglobulin M blocks infection. The revised architecture and collapse model are likely to be conserved across flaviviruses., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Flagellotropic bacteriophages engage flagella to reach the bacterial surface as an effective means to increase the capture radius for predation. Structural details of these viruses are of great interest given the substantial drag forces and torques they face when moving down the spinning flagellum. We show that the main capsid and auxiliary proteins form two nested chainmails that ensure the integrity of the bacteriophage head. Core stabilising structures are conserved in herpesviruses suggesting their ancestral origin. The structure of the tail also reveals a robust yet pliable assembly. Hexameric rings of the tail-tube protein are braced by the N-terminus and a β-hairpin loop, and interconnected along the tail by the splayed β-hairpins. By contrast, we show that the β-hairpin has an inhibitory role in the tail-tube precursor, preventing uncontrolled self-assembly. Dyads of acidic residues inside the tail-tube present regularly-spaced motifs well suited to DNA translocation into bacteria through the tail.

Objective: To determine the influence of nail characteristics on bacterial counts on the fingers of surgery personnel., Study Design: Randomized nonblinded controlled crossover study design., Sample Population: Veterinary students, small animal surgery technicians, small animal surgery interns/residents, and small animal surgery faculty in a veterinary teaching hospital (n = 21)., Methods: Subjects were randomized into one of 2 groups; group 1 wore nail polish (P) for 1 week and group 2 (control) had nonpolished (NP) fingernails. Each subject changed groups the following week. Fingernail lengths were measured each day and fingernail samples were collected before and after presurgical scrub and after surgery. Total bacterial counts (TBC) and suspected staphylococci were counted on blood agar media and mannitol salt agar. The association between bacterial counts and nail biting, position of the volunteer, duration of the surgery, whether the nail polish was chipped, duration of nail polish application, type of surgery, and handedness was tested. Log-transformed CFU counts were compared with a Student's t test and presence or absence of bacteria were compared using Fisher's exact test., Results: TBC, quantities of staphylococci, other gram-positive organisms, and gram-negative bacilli did not differ between P and NP personnel. The only variable associated with higher bacterial counts consisted of nail lengths greater than 2 mm., Conclusion: Nail polish did not influence bacterial counts and types of isolates, but nail length is a risk factor for increased bacterial counts. Based on our results, we recommend that nail length be kept under 2 mm., (© 2017 The American College of Veterinary Surgeons.)

Objective: To report a case of successful surgical removal of a guide wire lost during central venous catheterization., Case Summary: A 28 kg, 4-year-old female neutered mixed breed dog presented to the primary care veterinarian with diabetic ketosis. During the process of central venous catheterization, the guide wire was accidently released and the entire length of the guide wire slipped into the jugular vein. Due to the absence of nearby interventional radiology facilities, surgical intervention was proposed. An ultrasound was used to determine that the guide wire was located in the caudal vena cava extending caudally into the right internal iliac vein. Rommel tourniquets were placed around the iliac vein cranial to the bifurcation of the common iliac vein into the external and internal iliac veins. A venotomy was performed in the right common iliac vein and the guide wire was grasped with hemostats and gently removed while alternately relaxing the cranial then caudal tourniquets. During anesthesia, ventricular premature contractions were noted that varied in frequency with the dog's positioning. Postoperative color flow Doppler ultrasound evaluation of the caudal vena cava, right common, internal and external iliac veins, and right femoral vein was normal with no evidence of thrombosis. Several days postoperative the dog's diabetic ketosis and ventricular premature contractions had resolved and color flow Doppler ultrasound evaluation was normal with no evidence of thrombosis., New or Unique Information Provided: To the authors' knowledge, this is the first reported veterinary case of loss and subsequent surgical retrieval of a central venous catheter guide wire., (© Veterinary Emergency and Critical Care Society 2017.)

The assembly and regulation of viral capsid proteins into highly ordered macromolecular complexes is essential for viral replication. Here, we utilize crystal structures of the capsid protein from the smallest and simplest known viruses capable of autonomously replicating in animal cells, circoviruses, to establish structural and mechanistic insights into capsid morphogenesis and regulation. The beak and feather disease virus, like many circoviruses, encode only two genes: a capsid protein and a replication initiation protein. The capsid protein forms distinct macromolecular assemblies during replication and here we elucidate these structures at high resolution, showing that these complexes reverse the exposure of the N-terminal arginine rich domain responsible for DNA binding and nuclear localization. We show that assembly of these complexes is regulated by single-stranded DNA (ssDNA), and provide a structural basis of capsid assembly around single-stranded DNA, highlighting novel binding interfaces distinct from the highly positively charged N-terminal ARM domain.

Overlap chronic graft-versus-host disease (GVHD) associates both features of acute and chronic GVHD. Trigger factors for chronic GVHD are unclear. We describe two patients who received allogenic haematopoietic stem-cell transplantation, and who later developed overlap chronic GVHD after sun exposure. Available data from in vivo investigations suggest ultraviolet B radiation (UVB) has a beneficial effect on acute and chronic GVHD. The role of sun irradiation as a trigger for isomorphic cutaneous GVHD has been rarely reported in the literature. Herein, we demonstrate for the first time, using repetitive broadband phototesting, that UVB triggers chronic GVHD., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The financial success of academic medical centers depends largely on appropriate billing for resident-patient encounters. Objectives of this study were to develop an instrument for billing in internal medicine resident clinics, to compare billing practices among junior versus senior residents, and to estimate financial losses from inappropriate resident billing., Methods: For this analysis, we randomly selected 100 patient visit notes from a resident outpatient practice. Three coding specialists used an instrument structured on Medicare billing standards to determine appropriate codes, and interrater reliability was assessed. Billing codes were converted to US dollars based on the national Medicare reimbursement list. Inappropriate billing, based on comparisons with coding specialists, was then determined for residents across years of training., Results: Interrater reliability of Current Procedural Terminology components was excellent, with κ ranging from 0.76 for examination to 0.94 for diagnosis. Of the encounters in the study, 55% were underbilled by an average of $45.26 per encounter, and 18% were overbilled by an average of $51.29 per encounter. The percentages of appropriately coded notes were 16.1% for postgraduate year (PGY) 1, 26.8% for PGY-2, and 39.3% for PGY-3 residents (P < .05). Underbilling was 74.2% for PGY-1, 48.8% for PGY-2, and 42.9% for PGY-3 residents (P < .01). There was significantly less overbilling among PGY-1 residents compared with PGY-2 and PGY-3 residents (9.7% versus 24.4% and 17.9%, respectively; P < .05)., Conclusions: Our study reports a reliable method for assessing billing in internal medicine resident clinics. It exposed large financial losses, which were attributable to junior residents more than senior residents. The findings highlight the need for educational interventions to improve resident coding and billing.

It is thought that up to 50% of patients with cerebrovascular disease will have concurrent ischaemic heart disease. Dipyridamole co-formulated with aspirin has been shown to increase the relative reduction in risk of second stroke in patients with prior stroke/transient ischaemic attack beyond that obtaining with aspirin alone. We have sought to resolve the question of whether dipyridamole treatment increases the risk of cardiac adverse events in patients with co-existing ischaemic heart disease. The published literature, periodic safety update reports, the randomised controlled trials of antiplatelet agents in stroke prevention and those including dipyridamole in cardiovascular indications, have been reviewed and analysed. The early reports of serious adverse cardiac effect attributable to dipyridamole occurred in patients with severe coronary artery disease using dipyridamole as a stress test adjunct to cardiac imaging. The randomised controlled trials databases show no evidence of mortality and only isolated cases of significant cardiac morbidity attributable to dipyridamole at recommended oral doses in patients with ischaemic heart disease. We conclude that patients with cerebrovascular and mild to moderate concomitant ischaemic heart disease may be treated safely with dipyridamole for the secondary prevention of stroke.

In a post hoc analysis of the European Stroke Prevention Study 2 (ESPS2), we investigated whether dipyridamole given as antiplatelet drug in patients with TIA or stroke increases the risk of cardiac events. ESPS2 was a secondary prevention trial including 6602 patients with TIA or stroke. Patients were randomized into one of four treatment arms: 2 x 25 mg acetylsalicylic acid (ASA), 2 x 200 mg slow release dipyridamole (DP), the combination of DP and ASA and placebo. DP did not result in a higher number of cardiac events, e.g., angina pectoris, myocardial infarction or death. The combination of ASA plus DP was superior to either drug alone in the prevention of strokes.

The time course of changes in blood lactate concentration and ventilatory gas exchange was studied during an incremental exercise test on a cycle ergometer to determine if the lactate accumulation threshold (LT2) could be accurately estimated by the use of respiratory indices (VT2) in young athletes. LT2 was defined as the starting point of accelerated lactate accumulation. VT2 was identified by the second exponential increase in VE and the ventilatory equivalent for O2 uptake with a concomitant nonlinear increase in the ventilatory equivalent for CO2 output. Twelve trained subjects, aged 18-22 years, participated in this study. The initial power setting was 30 W for 3 min with successive increases of 30 W every minute except at the end of the test when the increase was reduced. Ventilatory flow (VE), oxygen uptake (VO2), carbon dioxide output (VCO2), and ventilatory equivalents of O2 and CO2 were determined during the last 30 s of every minute. Venous blood samples were drawn at the end of each stage of effort and analysed enzymatically for lactate concentration. After each test, LT2 and VT2 were determined visually by two investigators from the graphic results using a double-blind procedure. The results [mean (SEM)] indicate no significant difference between LT2 and VT2 expressed as VO2 [43.98 (1.70) vs 44.93 (2.39) ml.min-1 x kg-1], lactataemia [4.01 (0.28) vs 4.44 (0.37) mM.l-1], or heart rate [171 (3.36) vs 173 (3.11) min-1]. In addition, strong correlations were noted between the two methods for VO2 (r = 0.90, P < 0.001), lactataemia (r = 0.75, P < 0.01), and heart rate (r = 0.96, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

To study the effects of age and training on lactate production in older trained subjects, the lactate kinetics of highly trained cyclists [HT, n = 7; 65 (SEM 1.2) years] and control subjects with low training (LT, n = 7) and of similar age were compared to those of young athletes [YA, n = 7; 26 (SEM 0.7) years], during an incremental exercise test to maximum power. The results showed that the lactacidaemia at maximal oxygen uptake (VO2max) was lower for HT than for LT (P < 0.05) and, in both cases, lower than that of YA (P < 0.001). The respective values were HT: 3.9 (SEM 0.51), LT: 5.36 (SEM 1.12), and YA: 10.3 (SEM 0.63) mmol.l-1. At submaximal powers, however, the difference in lactacidaemia was not significant between HT and YA, although the values for lactacidaemia at VO2max calculated per watt and per watt normalized by body mass were significantly lower for HT (P < 0.001) and LT (P < 0.02). These results would indicate that the decline in power with age induced a decline in lactacidaemia. Yet this loss in power was not the only causative factor; indeed, our results indicated a complementary metabolic influence. In the older subjects training decreased significantly the lactacidaemia for the same submaximal power (P < 0.01) and from 60% of VO2max onwards (P < 0.05); as for YA it postponed the increase and accumulation of lactates. The lactate increase threshold (Thla-,1) was found at 46% VO2max for LT and at 56% VO2max for HT.(ABSTRACT TRUNCATED AT 250 WORDS)

With the Sequoia fixator, lengthenings can be achieved based on the clinical facts of the case. The device is a modular apparatus that can perform corrections in several planes, and, if necessary, in a septic environment. In our opinion, a "lengthener surgeon" is one who can foresee problems and take appropriate steps to prevent them. Likewise, the surgeon must act as the coordinator of an entire team. A successful lengthening is 5% surgery and 95% postoperative nursing and physiotherapy care. In the future, a number of changes will simplify postoperative management: 1. Composite carbon rings will make the frames radiolucent and one third lighter than those made of stainless steel. Automatic tensioners will help maintain steady tension on the wires. 2. Digital analysis of the callus will provide norms of consolidation, allowing faster fixator removal and conversion to an orthosis. 3. Incorporating the foot in the frame to overcome equinus will eliminate the need for tenotomy. We believe that monolateral and ring fixators can work together in certain locations. That is why we proposed, at the 18th Societé Internationale de Chirurgie Orthopédique et Traumatologique meeting, a combined monolateral-ring construct that can be used for lengthening throughout the proximal femoral metaphysis.

The operative approach and findings of 250 osteoplastic frontal sinusotomy operations performed from 1956 through 1972 at the Massachusetts Eye and Ear Infirmary are reviewed. Indications for surgery were symptomatic and/or complicated disease of the frontal sinus, including primary chronic sinusitis and osteoma or trauma with or without associated infection. Immediate postoperative complications were minor. Follow-up of at least three years was obtained in 83% of the patients, and 93% of these have no significant symptoms to date. A distressing problem of persistent postoperative frontal pain is discussed in detail. Revision surgery has been performed in 6% of patients due to recurrent frontal sinus infection. The reasons for failure are anlyzed, and recommendations are made to minimize the possibility of recurrence.

Two cases of ectopic openings of the common bile duct are reported. In one case there was a congenital short duct opening into DI, the presence of a spontaneous duodenobiliary reflux due to absence of the papilla being demonstrated by clinical and radiological examinations. The other patient had a long duct opening into D3 and no duodenobiliary reflux, but with an intact sphincter of Oddi explored in detail by means of combined choledochoduodenal manometry. These two cases demonstrate that the duodenal wall has only a moderate effect in preventing duodenobiliary reflux. The essential element is the sphincter of Oddi: if present, there is no reflux, if absent, reflux occurs.

A study was made of three groups of babies, one breast fed, one having Karitane Milk Food, the third homogenised milk. Blood sodium and urea were measured in the neonatal period. The urea levels were significantly higher in babies having homogenised milk compared with those fed Karitane or breast milk. Haemoglobin was measured in the neonatal period, and at 3, 6, 10 1/2 and 18 months. At six months, haemoglobin levels were significantly higher in Karitane milk fed than in homogenised milk fed babies. Serum cholesterol and triglyceride were measured in cord blood, and at 6 and 18 months of age. Serum triglyceride levels in babies on Karitane Milk Food were significantly higher than those on homogenised milk. Increments in weight, height and head circumference were compared. Karitane milk fed babies gained significantly more weight than breast fed between three and six months of age.