Single domain antibodies derived from ancient animals as broadly neutralizing agents for SARS-CoV-2 and other coronaviruses.

With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergent human virus since December 2019, the world population is susceptible to coronavirus disease 2019 (COVID-19). SARS-CoV-2 has higher transmissibility than the previous coronaviruses, associated by the ribonucleic acid (RNA) virus nature with high mutation rate, caused SARS-CoV-2 variants to arise while circulating worldwide. Neutralizing antibodies are identified as immediate and direct-acting therapeutic against COVID-19. Single-domain antibodies (sdAbs), as small biomolecules with non-complex structure and intrinsic stability, can acquire antigen-binding capabilities comparable to conventional antibodies, which serve as an attractive neutralizing solution. SARS-CoV-2 spike protein attaches to human angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells to initiate viral infection, serves as potential therapeutic target. sdAbs have shown broad neutralization towards SARS-CoV-2 with various mutations, effectively stop and prevent infection while efficiently block mutational escape. In addition, sdAbs can be developed into multivalent antibodies or inhaled biotherapeutics against COVID-19.

Vitamin C supplementation reduces the odds of developing a common cold in Republic of Korea Army recruits: randomised controlled trial.

INTRODUCTION: The Republic of Korea (ROK) military has a high incidence of respiratory diseases at training centres. Vitamin C has been reported to reduce the incidence of colds. For the purpose of preventing soldiers' respiratory diseases, this study aimed to investigate whether vitamin C intake can prevent common colds in the ROK Army soldiers. METHODS: This was a randomised, placebo-controlled, and double-blind trial of soldiers who enlisted in the Korea Army Training Centre for 30 days from 12 February to 13 March 2018. The study participants were divided into groups (vitamin C vs placebo). The military medical records were searched to determine whether the participants had a common cold. Multiple logistic regression analysis was performed to identify the association between vitamin C intake and diagnosis of common colds. In addition, subgroup analysis on the relationship between vitamin C intake and common cold according to smoking status, training camp and physical rank was conducted. RESULTS: A total of 1444 participants were included in our study. Of these participants, 695 received vitamin C (6000 mg/day, vitamin C group), while 749 participants received placebo (0 mg/day, placebo group). The vitamin C group had a 0.80-fold lower risk of getting a common cold than did the placebo group. Subgroup analyses showed that this effect was stronger among subjects in camp A, among never smokers and among those in physical rank 3. CONCLUSION: Vitamin C intake provides evidence to suggest that reducing the common colds in Korean Army soldiers. Our results may serve as a basis for introducing military healthcare policies that can provide vitamin C supplementation for military personnel in basic military training.

A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial☆.

BACKGROUND: Adjuvant chemotherapy and chemoradiotherapy are some of the standards of care for gastric cancer (GC). The Adjuvant chemoRadioTherapy In Stomach Tumors (ARTIST) 2 trial compares two adjuvant chemotherapy regimens and chemoradiotherapy in patients with D2-resected, stage II or III, node-positive GC. PATIENTS AND METHODS: The ARTIST 2 compared, in a 1:1:1 ratio, three adjuvant regimens: oral S-1 (40-60 mg twice daily 4 weeks on/2 weeks off) for 1 year, S-1 (2 weeks on/1 week off) plus oxaliplatin 130 mg/m2 every 3 weeks (SOX) for 6 months, and SOX plus chemoradiotherapy 45 Gy (SOXRT). Randomization was stratified according to surgery type (total or subtotal gastrectomy), pathologic stage (II or III), and Lauren histologic classification (diffuse or intestinal/mixed). The primary endpoint was disease-free survival (DFS) at 3 years; a reduction of 33% in the hazard ratio (HR) for DFS with SOX or SOXRT, when compared with S-1, was considered clinically meaningful. The trial is registered at clinicaltrials.gov (NCT0176146). RESULTS: A total of 546 patients were recruited between February 2013 and January 2018 with 182, 181, and 183 patients in the S-1, SOX, and SOXRT arms, respectively. Median follow-up period was 47 months, with 178 DFS events observed. Estimated 3-year DFS rates were 64.8%, 74.3%, and 72.8% in the S-1, SOX, and SOXRT arms, respectively. HR for DFS in the control arm (S-1) was shorter than that in the SOX and SOXRT arms: S-1 versus SOX, 0.692 (P = 0.042) and S-1 versus SOXRT, 0.724 (P = 0.074). No difference in DFS was found between SOX and SOXRT (HR 0.971; P = 0.879). Adverse events were as anticipated in each arm, and were generally well-tolerated and manageable. CONCLUSIONS: In patients with curatively D2-resected, stage II/III, node-positive GC, adjuvant SOX or SOXRT was effective in prolonging DFS, when compared with S-1 monotherapy. The addition of radiotherapy to SOX did not significantly reduce the rate of recurrence after D2 gastrectomy.

Report from the 20th annual Western Canadian Gastrointestinal Cancer Consensus Conference; Saskatoon, Saskatchewan; 28-29 September 2018.

The 20th annual Western Canadian Gastrointestinal Cancer Consensus Conference was held in Saskatoon, Saskatchewan, 28-29 September 2018. This interactive multidisciplinary conference is attended by health care professionals from across Western Canada (British Columbia, Alberta, Saskatchewan, and Manitoba) who are involved in the care of patients with gastrointestinal cancers. In addition, invited speakers from other provinces participate. Surgical, medical, and radiation oncologists, and allied health care professionals participated in presentations and discussion sessions for the purpose of developing the recommendations presented here. This consensus statement addresses current issues in the management of colorectal cancers.

Descending and tonotopic projection patterns from the auditory cortex to the inferior colliculus.

The inferior colliculus (IC) receives many corticofugal projections, which can mediate plastic changes such as shifts in frequency tuning or excitability of IC neurons. While the densest projections are found in the IC's external cortices, fibers originating from the primary auditory cortex (AI) have been observed throughout the IC's central nucleus (ICC), and these projections have shown to be organized tonotopically. Some studies have also found projections from other core and non-core cortical regions, though the organization and function of these projections are less known. In guinea pig, there exists a non-core ventrorostral belt (VRB) region that has primary-like properties and has often been mistaken for AI, with the clearest differentiating characteristic being VRB's longer response latencies. To better understand the auditory corticofugal descending system beyond AI, we investigated if there are projections from VRB to the ICC and if they exhibit a different projection pattern than those from AI. In this study, we performed experiments in ketamine-anesthetized guinea pigs, in which we positioned 32-site electrode arrays within AI, VRB, and ICC. We identified the monosynaptic connections between AI-to-ICC and VRB-to-ICC using an antidromic stimulation method, and we analyzed their locations across the midbrain using three-dimensional histological techniques. Compared to the corticocollicular projections to the ICC from AI, there were fewer projections to the ICC from VRB, and these projections had a weaker tonotopic organization. The majority of VRB projections were observed in the caudal-medial versus the rostral-lateral region along an isofrequency lamina of the ICC, which is in contrast to the AI projections that were scattered throughout an ICC lamina. These findings suggest that the VRB directly modulates sound information within the ascending lemniscal pathway with a different or complementary role compared to the modulatory effects of AI, which may have implications for treating hearing disorders.

Axitinib versus sorafenib in advanced renal cell carcinoma: subanalyses by prior therapy from a randomised phase III trial.

BACKGROUND: In the AXIS trial, axitinib prolonged progression-free survival (PFS) vs sorafenib in patients with advanced renal cell carcinoma (RCC) previously treated with sunitinib or cytokines. METHODS: In post hoc analyses, patients were grouped by objective response to prior therapy (yes vs no), prior therapy duration (< vs ⩾median), and tumour burden (baseline sum of the longest diameter < vs ⩾median). PFS and overall survival (OS), and safety by type and duration of prior therapy were evaluated. RESULTS: Response to prior therapy did not influence outcome with second-line axitinib or sorafenib. PFS was significantly longer in axitinib-treated patients who received longer prior cytokine treatment and sorafenib-treated patients with smaller tumour burden following sunitinib. Overall survival with the second-line therapy was longer in patients who received longer duration of prior therapy, although not significant in the sunitinib-to-axitinib sequence subgroup; OS was also longer in patients with smaller tumour burden, but not significant in the cytokine-to-axitinib sequence subgroup. Safety profiles differed modestly by type and duration of prior therapy. CONCLUSIONS: AXIS data suggest that longer duration of the first-line therapy generally yields better outcome with the second-line therapy and that lack of response to first-line therapy does not preclude positive clinical outcomes with a second-line vascular endothelial growth factor-targeted agent in patients with advanced RCC.

Gingko biloba extracts protect auditory hair cells from cisplatin-induced ototoxicity by inhibiting perturbation of gap junctional intercellular communication.

Gap junctional intercellular communication (GJIC) may play an important role in the hearing process. Cisplatin is an anticancer drug that causes hearing loss and Gingko biloba extracts (EGb 761) have been used as an antioxidant and enhancer for GJIC. The purpose of this study was to examine the efficiency of EGb 761 in protecting against cisplatin-induced apoptosis and disturbance of GJIC. House Ear Institute-Organ of Corti 1 auditory cells were cultured and treated with cisplatin (50 µM) and EGb (300 µg/ml) for 24h, and then analyzed by immunocytochemistry (Annexin V/propidium iodide) and Western blots. GJIC was evaluated by scrape-loading dye transfer (SLDT). Basal turn organ of Corti (oC) explants from neonatal (p3) rats were exposed to cisplatin (1-10 µM) and EGb (50-400 µg/ml). The number of intact hair cells was counted by co-labeling with phalloidin and MyoVIIa. EGb prevented cisplatin-induced apoptosis in immunostaining and decreased caspase 3 and poly-ADP-ribose polymerase bands, which were increased in cisplatin-treated cells in Western blots. EGb prevented abnormal intracellular locations of connexin (Cx) 26, 30, 31, and 43 in cells treated with cisplatin and increased quantities of Cx bands. EGb also prevented cisplatin-induced disturbance of GJIC in SLDT. In oC explants, EGb significantly prevented hair cell damage induced by cisplatin. In animal studies, EGb significantly prevented cisplatin-induced hearing loss across 16 and 32 kHz. These results show that cisplatin induces ototoxicity including hearing loss as well as down-regulation of GJIC and inhibition of Cxs in auditory cells. EGb prevents hearing loss in cisplatin-treated rats by inhibiting down-regulation of Cx expression and GJIC. The disturbance of GJIC or Cx expression may be one of the important mechanisms of cisplatin-induced ototoxicity.

A combination of cilostazol and Ginkgo biloba extract protects against cisplatin-induced Cochleo-vestibular dysfunction by inhibiting the mitochondrial apoptotic and ERK pathways.

Cisplatin (cis-diammine-dichloroplatinum; CDDP) is an anticancer drug that induces significant hearing loss and balance dysfunction as side effects. Cilostazol (CS, 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3, 4-dihydro-2-(1H)-quinolinone) has neuroprotective and antioxidant effects, whereas Ginkgo biloba extract (GbE) has preventive effects on CDDP-induced hearing loss in rats, and GbE enhances the antiatherogenic effect of CS by inhibiting the generation of reactive oxygen species (ROS). The purpose of this study was to investigate the effects of renexin (RXN), which contains GbE and CS, against CDDP-induced cochleo-vestibular dysfunction in rats and to elucidate the mechanism underlying the protective effects of RXN on auditory cells. Rats intraperitoneally injected with CDDP exhibited an increase in hearing threshold and vestibular dysfunction, which agreed with hair cell damage in the Organ of Corti and otoliths. However, these impairments were significantly prevented in a dose-dependent manner by pre- and co-treatment with RXN, and these preventive effects in RXN-treated rats were more prominent than those in GbE-treated rats. In a CDDP pharmacokinetic study, platinum concentration was very similar between CDDP-only treated and RXN+CDDP cotreated rats. RXN markedly attenuated CDDP-induced intracellular ROS and significantly reduced CDDP-activated expression of p-extracellular regulated kinase (ERK), BAX, cytochrome c, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, but increased BCL-XL expression. These results show that RXN may have a synergistic effect by strongly protecting hearing and vestibular dysfunction induced by CDDP by inhibiting ROS production, mitochondrial pathways and the ERK pathway, without interfering with CDDP pharmacokinetics. Therefore, RXN could potentially be used to reduce CDDP-related hearing loss and dizziness.

Hepatic embolotherapy in interventional oncology: technology, techniques, and applications.

Embolotherapy continues to play a growing role in the management of primary and secondary hepatic malignancies. In this review article, we examine the basis of therapy with a focus on neovascularization, which makes treatments via the hepatic artery possible. An overview of the three generations of embolic and therapeutic agents follows. The techniques, technologies, and complications of bland embolization, transarterial chemoembolization, drug-eluting beads, and selective internal radiotherapy are covered to give the reader an overview of this exciting field in interventional radiology.

Recurrence after successful treatment among patients with multidrug-resistant tuberculosis.

A retrospective review was conducted of patients with multidrug-resistant tuberculosis (MDR-TB) to elucidate the rate of recurrence after successful treatment. Of 123 MDR-TB patients, 90 were declared as 'cured' or 'treatment completed' after individualised treatment; four (4.4%) experienced recurrence. All patients with recur- rent MDR-TB were documented as 'treatment completed' after treatment. Recurrence of MDR-TB is possible after successful treatment, particularly among those documented as 'treatment completed'.

Potato (Solanum tuberosum L. cv. Gogu valley) protein as an antimicrobial agent in the diets of broilers.

Two experiments were conducted to evaluate potato protein (PP, experiment 1) and refined PP (RPP, experiment 2) obtained from Gogu valley tubers as an antimicrobial agent in broiler diets. In both the experiments, 1-d-old male Ross 308 chicks were allotted to 5 treatments and performance, nutrient retention, and microbial populations in excreta and cecum were studied. Dietary treatments were as follows: basal diet (negative control, NC), basal diet with antibiotic (positive control, PC, 10 mg/kg of avilamycin), and low, medium, or high levels of PP (0.25, 0.50, and 0.75%, respectively, in experiment 1) or RPP (200, 400, and 600 mg/kg, respectively, in experiment 2). The overall gain and retention of DM (d 20 to 21) and CP (d 20 to 21 and d 41 to 42) were greater in birds fed PC and high PP diets than birds fed the NC diet. Population of total aerobic bacteria and coliforms was lowest in the cecum and excreta of birds fed the PC diet and highest in birds fed the NC diet. An increase in dietary PP linearly improved BW gain, feed intake, and feed conversion ratio during starter phase and overall BW gain. Also, there was linear improvement in retention of DM (d 20 to 21) and CP (d 20 to 21 and d 41 to 42) and reduced populations of total aerobic bacteria and coliforms in the cecum (d 42) and excreta (d 28 and 42) due to an increase in dietary PP. In the second experiment, the PC diet and diets with increasing levels of RPP had no effect on performance and nutrient retention. Birds fed the PC diet had the lowest microbial population in excreta and cecum, whereas the population of total aerobic bacteria and coliforms in excreta and cecum decreased (linear, P < 0.05) as the level of RPP was increased in the diet. These results suggest that both PP and RPP obtained from Gogu valley potato tubers have in vivo antimicrobial activity.

A case of ricin poisoning following ingestion of Korean castor bean.

Ricin is a member of a group of protein toxins whose cytosolic target is the 28S rRNA of the 60S ribosomal subunit. It was recently introduced as a weapon of terrorism in some countries. There is little evidence about the mechanism, diagnosis and treatment of ricin poisoning. The case history is reported of a patient with ricin poisoning who presented with nausea and vomiting following ingestion of Korean castor bean.

A clinical trial and molecular study of photoadaptation in vitiligo.

BACKGROUND: Photoadaptation to ultraviolet (UV) B phototherapy is due to both pigmentary and nonpigmentary influences. OBJECTIVES: To measure photoadaptation in vitiliginous skin and to compare it with normal pigmented skin. METHODS: Seventeen patients with Fitzpatrick skin phototypes III-VI with vitiligo received six to nine UVB treatments, two to three times weekly. Minimal erythema dose (MED) testing was done at baseline and after all treatments; the percentage change in MED was analysed as a measure of photoadaptation. The percentage decrease in cyclobutane pyrimidine dimers (CPDs) over 24 h after a single exposure of 1 MED was analysed on vitiliginous and normal skin. RESULTS: The mean +/- SD percentage change in MED from before to after treatments was: treated vitiliginous skin 28.5 +/- 39.9% (P = 0.015), treated normal skin 35.9 +/- 49.9% (P = 0.015), untreated vitiliginous skin 11.9 +/- 22.6% (P =0.070), untreated normal skin 25.1 +/- 41.3% (P = 0.041). Of these patients, two-thirds had a positive percentage change in MED (photoadaptation). The mean amount of CPDs induced per megabase of DNA immediately after exposure was significantly higher in vitiliginous skin. The mean +/- SD percentage decrease in CPDs (rate of repair) in 24 h was 35.7 +/- 26.8% in vitiliginous skin (P = 0.027) and 46.2 +/- 19.5% in normally pigmented skin (P = 0.001); no difference was noted in the repair in vitiliginous skin compared with normal skin (P = 0.4). CONCLUSIONS: Photoadaptation in vitiliginous and normal skin was observed in two-thirds of patients. Vitiliginous skin had significantly more CPDs following UVB exposure; the rate of repair of UVB-induced DNA damage was equivalent to that in normal skin.

Effects of phase duration and pulse rate on loudness and pitch percepts in the first auditory midbrain implant patients: Comparison to cochlear implant and auditory brainstem implant results.

The auditory midbrain implant (AMI), which is designed for stimulation of the inferior colliculus (IC), is now in clinical trials. The AMI consists of a single shank array (20 contacts) and uses a stimulation strategy originally designed for cochlear implants since it is already approved for human use and we do not yet know how to optimally activate the auditory midbrain. The goal of this study was to investigate the effects of different pulse rates and phase durations on loudness and pitch percepts because these parameters are required to implement the AMI stimulation strategy. Although each patient was implanted into a different region (i.e. lateral lemniscus, central nucleus of IC, dorsal cortex of IC), they generally exhibited similar threshold versus phase duration, threshold versus pulse rate, and pitch versus pulse rate curves. In particular, stimulation with 100 mus/phase, 250 pulse per second (pps) pulse trains achieved an optimal balance among safety, energy, and current threshold requirements while avoiding rate pitch effects. However, we observed large differences across patients in loudness adaptation to continuous pulse stimulation over long time scales. One patient (implanted in dorsal cortex of IC) even experienced complete loudness decay and elevation of thresholds with daily stimulation. Comparing these results with those of cochlear implant and auditory brainstem implant patients, it appears that stimulation of higher order neurons exhibits less and even no loudness summation for higher rate stimuli and greater current leakage for longer phase durations than that of cochlear neurons. The fact that all midbrain regions we stimulated, which includes three distinctly different nuclei, exhibited similar loudness summation effects (i.e. none for pulse rates above 250 pps) suggests a possible shift in some coding properties that is affected more by which stage along the auditory pathway rather than the types of neurons are being stimulated. However, loudness adaptation occurs at multiple stages from the cochlea up to the midbrain.

Potato (Solanum tuberosum L. cv. Gogu valley) protein as a novel antimicrobial agent in weanling pigs.

A total of 280 weaned pigs (Landrace x Yorkshire x Duroc) were used in a 28-d growth study to investigate the effect of feeding different levels of potato proteins on growth performance, nutrient digestibility, immune response, small intestinal morphology, and bacterial populations in feces and large intestine. Pigs (initially 6.42 +/- 0.74 kg of BW and 23 +/- 3 d of age) were randomly allotted to 5 treatments on the basis of BW, each treatment composed of 4 pens, each pen having 14 pigs. Dietary treatments included positive control (PC; basal diet + 150 mg/kg apramycin and 10 mg/ kg colistin sulfate); and potato protein (PP), consisting of the basal diet with 0, 0.25, 0.50, or 0.75% of potato protein. Diets were fed in 2 phases: phase I (d 0 to 14 postweaning) and phase 2 (d 14 to 28 postweaning). Potato protein was extracted from a value-added type of the new potato variety, Solanum tuberosum L. cv. Gogu valley, and was shown to have a minimum inhibitory concentration of 300 to 500 mug/mL. Performance of PC was compared with 0.25 to 0.75% PP, whereas linear and quadratic trends of increasing PP (0 to 0.75% PP) were tested. Over the 28-d trial, pigs fed the PC diets showed improved overall ADG (P < 0.05) and G:F (P = 0.090) compared with pigs fed PP, whereas increasing levels of PP linearly improved ADG (P < 0.05), ADFI (P = 0.052), and G:F (P = 0.098). The digestibility of DM and CP in both the phases was greater in PC than PP, and feeding of PP linearly improved the DM digestibility (P < 0.05) in phase II. The bacterial populations in the feces of pigs fed PC and PP were comparable, except for total bacteria and coliform bacteria in the feces at d 14 and 28, which were decreased in PC; and feeding of PP was effective in linearly reducing the populations of microbes in feces and contents of cecum, colon, and rectum. There was linear increase (P < 0.10) in skin-fold thickness in response to phytohemagglutinin with an increase in PP levels. Haemagglutinin titers on d 21 were greater (P = 0.054) in PC, and at d 28 the haemagglutinin titers were quadratically affected in pigs fed PP (P = 0.070). There was a trend toward a decrease in crypt depth (P = 0.068) and a greater villus height:crypt depth ratio (P = 0.082) of ileum in PC compared with PP. These results suggest that PP may be an alternative to medicated feed with antibiotics because it showed antimicrobial activity by effectively reducing the population of coliform bacteria and also improved the performance of weanling pigs.

Bikaverin and fusaric acid from Fusarium oxysporum show antioomycete activity against Phytophthora infestans.

AIMS: To isolate and identify antioomycete substances from Fusarium oxysporum EF119 against Phytophthora infestans and to investigate their antimicrobial activities against various plant pathogenic bacteria, oomycetes and true fungi. METHODS AND RESULTS: Two antioomycete substances were isolated from liquid cultures of F. oxysporum EF119, which shows a potent disease control efficacy against tomato late blight caused by P. infestans. They were identified as bikaverin and fusaric acid by mass and nuclear magnetic resonance spectral analyses. They inhibited the mycelial growth of plant pathogenic oomycetes and fungi. Fusaric acid also effectively suppressed the cell growth of various plant pathogenic bacteria, but bikaverin was virtually inactive. Treatment with bikaverin at 300 microg ml(-1) suppressed the development of tomato late blight by 71%. Fusaric acid provided effective control against tomato late blight and wheat leaf rust over 67% at concentrations more than 100 microg ml(-1). CONCLUSIONS: Both bikaverin and fusaric acid showed in vitro and in vivo antioomycete activity against P. infestans. SIGNIFICANCE AND IMPACT OF THE STUDY: Fusarium oxysporum EF119 producing both bikaverin and fusaric acid may be used as a biocontrol agent against tomato late blight caused by P. infestans.

An efficient cryopreservation procedure for potato (Solanum tuberosum L.) utilizing the new ice blocking agent, Supercool X1000.

Cryopreservation has been recognized as a practical and efficient tool for long-term storage of vegetatively propagated plants. This study was conducted to investigate effects of modified vitrification techniques on cryopreservation of potato. In vitro plants of potato cultivars "Superior" and "Atlantic" were cold acclimated, and axillary buds were precultured, osmoprotected, exposed to PVS-2 solution, plunged into liquid nitrogen, thawed, and finally planted in the regeneration medium. In the modified vitrification technique an ice-blocking agent, Supercool X1000, was added with PVS-2 solution. Cold acclimation affected survival of cryopreserved shoot tips, and the highest survival (46.7%) was obtained after 3 weeks of acclimation at 10 degrees C. Shoot tips exposed to 2M glycerol plus 0.6M sucrose for 40 min gave 51.5% and 11.7% survival in "Atlantic" and "Superior" at 10 degrees C, respectively. Cold acclimated and osmoprotected shoot tips were dehydrated with PVS-2 containing different concentrations of Supercool X1000 prior to a plunge into liquid nitrogen. Treatments with 0.1% and 1% of Supercool X1000 significantly improved survival by 55% in "Superior" and 71.3% in "Atlantic", respectively. After cryopreservation, vitrified shoot tips resumed growth within a week in a medium (1 mg l(-1) GA(3), 0.5 mg l(-1) zeatin, and 0.1 mg l(-1) IAA) with a low level of Pluronic F-68 (0.005%) and survival was 33.7% higher in "Atlantic" and 14.7% higher in "Superior" than the control (without Pluronic F-68).

Refractory livedoid vasculitis responding to PUVA: a report of four cases.

Livedoid vasculitis is a chronic disease characterized by recurrent painful irregularly shaped ulcers, which heal with scars, most commonly located on feet or lower extremities. This condition is often resistant to the therapy. We report four cases with refractory livedoid vasculitis that responded to systemic psoralens and ultraviolet A radiation therapy.

Predicting significant hyperbilirubinaemia and early discharge for glucose-6-phosphate dehydrogenase deficient newborns.

INTRODUCTION: This study aims to assess the usefulness of day 3 (49 to 72 hours) pre-phototherapy total serum bilirubin (TSB) in predicting subsequent significant hyperbilirubinaemia (SHB) and the feasibility of early discharge for term and near-term glucose-6-phosphate dehydrogenase (G6PD) deficient newborns. MATERIALS AND METHODS: This prospective cohort study involved in born G6PD deficient neonates who were > or = 35 weeks and weighted > or = 2000 g at birth. TSB levels and phototherapy requirements in their first two weeks of life were studied. Day 3 pre-phototherapy TSB in the subgroup weighing > or = 2500 g at birth was analysed for its value in predicting subsequent SHB. RESULTS: Of the 129 neonates, 58 (45%) required phototherapy in the first week. Of these, only 4 patients (3.1%) needed phototherapy to be restarted in the second week. Seventy-one (55%) neonates did not require phototherapy at all. In the absence of SHB in the first week, the probability of its development in the second week was zero (95% confidence interval, 0 to 0.057). In the subgroup weighing > or = 2500 g at birth, day 3 pre-phototherapy TSB < or = 154 umol/L predicted no measurable risk of subsequent SHB (sensitivity, 100%; 95% confidence interval, 91.4% to 100%; negative predictive value, 100%; 95% confidence interval, 86.7% to 100%). CONCLUSIONS: G6PD deficient newborns without SHB in their first week of life were at no measurable risk of its development in the second week. Day 3 pre-phototherapy TSB in the subgroup weighing > or = 2500 g was useful for predicting the risk of subsequent SHB. Low-risk infants, thus identified, may be eligible for discharge on or before day 7 of life. Evidence-based early discharge can decrease the social and financial burden of G6PD deficiency in Singapore.