Recently it has been reported that the non-lymphoid cells in the inflammatory tissues express ectopically the activation-induced cytidine deaminase (AID) gene that induces somatic hypermutations, not only AZD2014 at the immunoglobulin (Ig) gene variable regions in germinal centre B lymphocytes
but also at coding regions in TP53. Real-time polymerase chain reaction (PCR) analyses revealed more than half (five of nine) of the RA-FLS lines we established showed the markedly increased expression of AID. AID transcription in RA-FLS was augmented by tumour necrosis factor (TNF)-alpha and even by physiological concentration of beta-oestradiol that could not induce AID transcription in osteoarthritis-FLS. Furthermore, AID-positive RA-FLS presented a higher frequency of somatic mutations in TP53. Cytological and immunohistochemical analyses demonstrated clearly the ectopic
expression of AID in the FLS at the RA synovium. These data suggested strongly a novel consequence of RA; the ectopic expression of AID in RA-FLS causes the somatic mutations and dysfunction of TP53, leading to acquisition of tumour-like properties by RA-FLS.”
“A germplasm safeguard programme was set up with 19 grapevine varieties considered as indigenous to northeastern Italy. To better estimate how genetic AZD7762 inhibitor structure can be used to obtain a conservation perspective of local varieties, genetic variability was examined at 30 nuclear and 3 chloroplast polymorphic microsatellite loci in the native varieties plus 7 European cultivars taken as reference. The genetic profiles of all the cultivars were searched for possible parentage relationships and several suspected Tariquidar in vitro cases of the same variety having different names were investigated. The alleles shared at the loci suggest a parent-offspring relationship between Merlot and Cabernet Franc, ‘Gruaja’ and ‘Negrara Veronese’, and Marzemina Nera and Marzemina Bianca. Alleles at the 30 nuclear loci are consistent with Raboso Veronese being the progeny of Marzemina Bianca and Raboso Piave. Chloroplast-specific haplotypes were singled out for the first time in this indigenous germplasm and should be considered typical of the
region. It is hypothesized that there are many specific haplotypes for the local varieties due to a past contribution of wild grapevine to the cultivated gene pool. The majority of investigated cultivars were demonstrated to constitute an independent source of genetic variation, and therefore a possible valuable resource of genetic traits for breeders.”
“In rats, an injection of streptozotocin (STZ) elevated blood levels of glucose 4 weeks later (STZ-induced diabetes) and an over-production of microvessels of retinal and choroidal capillaries of eyes developed. A previous study has shown that administration of Stephania tetrandra S. Moore (STSM) in culture prevented the over-production of microvessels of those capillaries of STZ-induced diabetes in vitro.
Lupus anticoagulant studies were negative. Superwarfarin toxicity was suspected and confirmed with an anticoagulant poison panel positive for brodifacoum. The patient was hospitalized and successfully treated with fresh frozen plasma, cryoprecipitate and vitamin K. In conclusion, paradoxical thrombosis and hemorrhage should raise the suspicion for superwarfarin toxicity in the appropriate clinical setting. Further studies are required to define the management of these patients. Blood Coagul Fibrinolysis 24:202-204 (C) 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.”
NAD(+)-dependent formate dehydrogenase FDH1 gene (fdh1), cloned from Candida boidinii, was expressed in the ldh-deleted CA4P mutant of Enterobacter
aerogenes IAM1183 strain. The plasmid of pCom10 driven by the PalkB promoter was used to construct the fdh1 expression system and thus introduce a new dihydronicotinamide adenine dinucleotide (NADH) regeneration pathway from formate in the ldh-deleted mutant. The knockout of NADH-consuming lactate pathway affected the whole cellular metabolism, and the hydrogen yield increased by 11.4% compared with the wild strain. Expression of fdh1 in the ldh-deleted mutant caused lower final cell concentration and final pH after 16 h cultivation, and finally resulted in 86.8% of increase in hydrogen yield per mole consumed glucose. The analysis of cellular metabolites and estimated redox state balance in the fdhl-expressed strain showed that more excess
of reducing power was formed by Selleckchem HSP990 the rewired NADH regeneration pathway, changing the metabolic distribution and promoting the hydrogen production.”
“Residual disease after cytoreductive surgery is an important prognostic factor in patients with advanced stage epithelial ovarian cancer (EOC). Aggressive surgical procedures necessary to achieve maximal cytoreduction are inevitably associated with postoperative morbidity and mortality.\n\nTo determine causes of postoperative mortality (POM) after surgery for EOC all postoperative deaths in the southwestern part of the Netherlands over a 17-year period were identified and analysed by reviewing medical notes.\n\nBetween Epigenetic Reader Do inhibitor 1989 and 2005, 2434 patients under-went cytoreductive surgery for EOC. Sixty-seven patients (3.1%) died within 30 days after surgery. Postoperative mortality increased with age from 1.5% (26/1765) for the age group 20-69 to 6.6% (32/486) for the age group 70-79 and 9.8% (18/183) for patients aged 80 years or older. Pulmonary failure (18%) and surgical site infection (15%) were the most common causes of death. Only a quarter of deaths resulted from surgical site complications.\n\nOur results suggest that causes of postoperative mortality after surgery for EOC are very heterogeneous.
“Introduction Peripartal cardiomyopathy is a rare, life-threatening complication previously healthy mother. Incidence of this disease ranges 1 to 3000 to 4000 births [1,2]. Diagnosis is based on the next criteria: weakness of myocard in peripartal period (4 weeks prior to 5 months after delivery), the inability to find out the reasons
leading to heart failure, the absence of heart disease up to 4 weeks before delivery, as well as the absence electrocardiographic seen systolic dysfunction of left ventricular before pregnancy .\n\nCase report 1 Patient was a few days after discharge complaining of feeling of fatigue, dyspnea and shortness of breath, especially when she lies on her back or at the slightest exertion, dry cough and oedema of the legs and abdomen. Fourteenth day after birth she is admitted as an emergency in the intensive care unit in Institute of cardiovascular
disease of Vojvodina with symptoms and SYN-117 chemical structure signs of global heart failure caused by postpartal dilated cardiomyopathy. She doesn’t have any cardiovascular disease or investigations about cardiovascular system before.\n\nCase report 2 Mothers aged 26 years, labored in 38 gestational week (GW). The first 2 days postpartum subjectively and objectively was good. On the third day after cesarean section she reported a sudden dispnea, ortopnea, fatigue and chest pain. Shortly thereafter she reported blood in her sputum. After internal, pulmological and GS-9973 order cardiological examinations, and after clinical and laboratory findings, x-ray lung and echocardiography, doctors confirmed the diagnosis of dilated cardiomyopathy and the third degree of mitral insufficiency. Cardiologist suggest moving patient to the intensive care unit in Institute of cardiovascular disease in Sremska Kamenica. Adequate therapy leads to withdrawal symptoms.\n\nConclusion Peripartal cardiomyopathy although still unknown cause, is a life-threatening complication of childbirth. Aim of our report is to emphasize the
importance of early echocardiography in sudden cardiac decompensation in the peripartal period, and to emphasize importance of multi-disciplinary approach to this kind of patients.”
“In order to reach higher selleck products broiler performance, farmers target losses reduction. One way to make this possible is by rearing sexed broilers as male and female present diverse performance due to their physiological differences. Birds from different genetic strain also have a distinct performance at the same age. Considering that sexed flocks may present higher performance this study aimed to identify one-day-old chicks’ sex throughout their vocalization. This research also investigated the possibility of identifying the genetic strain by their vocalization attributes. A total of 120 chicks, half of them were from Cobb (R) genetic strain and the other half from Ross (R) genetic strain.
Mutations in any of the succinate dehydrogenase (SDH) complex subunit genes (SDHA, SDHB, SDHC, SDHD) can lead to PCCs and PGLs with variable penetrance, as can mutations in the subunit cofactor, SDHAF2. Recently, two additional genes have been identified, TMEM127 and MAX. Although these tumors are rare in the selleck general population, occurring in two to eight per million people, they are more commonly associated with an inherited mutation than any other cancer type. This review summarizes the known germline and somatic mutations leading to the development of PCC and PGL, as well as biochemical profiling for PCCs/PGLs and screening of mutation carriers.”
caused by limbal stem cell deficiency (LSCD) is a prevailing disorder worldwide. Clinical outcomes for LSCD therapy using amniotic membrane (AM) are unpredictable. Hydrogels can eliminate limitations of standard therapy for LSCD, because they present all the advantages of AM (i.e. biocompatibility, inertness and a biodegradable structure) but unlike AM, they are structurally uniform and can be easily manipulated to alter mechanical and physical properties. Hydrogels can be delivered with minimum trauma to the ocular surface and do not require extensive LOXO-101 purchase serological screening before clinical application. The hydrogel structure is also amenable to modifications which direct stem cell fate.
In this focussed review we highlight hydrogels as biomaterial substrates which may replace and/or complement AM in the treatment of LSCD.”
“Herein, a novel Pluronic F127/graphene nanosheet (PF127/GN) hybrid was prepared via an one-pot process including the simultaneous reduction of graphene oxide and assembly of PF127 and GN. The nanohybrid exhibits high water dispersibility and stability in physiological environment with the hydrophilic chains of PF127 extending to the solution while the hydrophobic segments anchoring at the surface of graphene via hydrophobic interaction. The PF127/GN nanohybrid is found to be capable of effectively encapsulating doxorubicin (DOX) with ultrahigh drug-loading efficiency (DLE; 289%, w/w) and exhibits a Z-IETD-FMK concentration pH responsive drug release behavior. The superb DLE of the PF127/GN nanohybrid relies on the introduction of GN which is structurally compatible with DOX. Cellular toxicity assays performed on human breast cancer MCF-7 cells demonstrate that the PF127/GN nanohybrid displays no obvious cytotoxicity, whereas the PF127/GN-loaded DOX (PF127/GN/DOX) shows remarkable cytotoxicity to the MCF-7. Cell internalization study reveals that PF127/GN nanohybrid facilitates the transfer of DOX into MCF7 cells, evidenced by the image of confocal laser scanning microscopy.
An isolation process has been proposed, but limits of differential centrifugations as washing step and isolation technique
were also evidenced. This study clearly shows C188-9 JAK/STAT inhibitor the need for a continuous production and extraction process of SNC.”
“A fast and generic method has been developed for the simultaneous monitoring of > 250 pesticides and veterinary drugs (VDs) in animal feed. A ‘dilute-and-shoot’ extraction with water and acetonitrile (1 % formic acid) followed by a clean-up step with Florisil cartridges was applied. The extracts were analysed by ultra-high performance liquid chromatography coupled to hybrid analyser quadrupole-time-of-flight mass spectrometry using both positive and negative electrospray ionisation. The detection of the residues was accomplished by retention time and accurate mass using an in-house database. The identification of the detected compounds was carried out by searching of fragment ions for each compound and isotopic pattern. The optimised method was validated and recoveries ranged from 60 % to 120 % at three concentrations (10, 50 and 100 mu g kg(-1)) for 30 %, 68 % and 80 % of compounds, respectively, included in the database (364) in chicken feed. Document SANCO 12495/2011 and Directive 2002/657/CE were used as guidelines for method validation. Intra-day and inter-day precisions, expressed as relative standard
deviations, were lower than 20 % for more than 90 % of compounds. The limits of quantification ranged from find more 4 to 200 mu g kg(-1) for most analytes, which are sufficient to verify compliance of products with legal tolerances. The applicability of the procedure was further tested
on different types of feed (chicken, hen, rabbit and horse feed), evaluating recoveries and repeatability. Finally, the method was applied to the analysis of 18 feed samples, detecting some VDs (sulfadiazine, trimethoprim, robenidin and monensin Na) and only one pesticide (chlorpyrifos).”
“Thalassemia is the most common genetic disorder in Iran. Some a-globin genotypes leading to Hb H disease may cause severe anemia and dependence on regular blood transfusions. In this study, 40 patients Autophagy Compound Library cost were analyzed for the molecular basis and the genotype-phenotype correlation of Hb H disease in Iran. alpha-Globin molecular analysis was performed by polymerase chain reaction (PCR) followed by agarose gel electrophoresis, reverse hybridization test strips or DNA sequencing. The most frequently observed alpha-globin genotypes were -alpha(3.7)/- -(MED) in 10 patients (25%), – -(20.5)/alpha(-5nt)alpha in six patients (15%) and – -(20.5)/-alpha(3.7) in four patients (10%). A subset of the identified Hb H genotypes, including – -(MED)/alpha(CS)alpha, – -(MED)/alpha(PolyA2)alpha and alpha(CS)alpha/alpha(CS)alpha, was associated with a need for regular or irregular blood transfusions.
Treatment response was defined as 50% reduction in depressive symptoms at any point during the 12-week trial. One-hundred-forty-eight gene transcripts were significantly associated (1.2-fold, adjusted p <= 0.01) with response to infliximab and were distinct from placebo responders. Transcripts predictive of infliximab response were associated with gluconeogenesis and cholesterol transport, and were enriched in a network regulated by hepatocyte nuclear factor (HNF)4-alpha, a transcription factor involved in gluconeogenesis and cholesterol and lipid homeostasis.
Of the 148 transcripts differentially expressed at baseline, 48% were significantly regulated over time PARP inhibitor trial in infliximab
responders, including genes related to gluconeogenesis and the HNF4-alpha network, indicating that these predictive genes were responsive to infliximab. Responders also demonstrated inhibition of genes related to apoptosis through TNF signaling at 6 h and 24 h after infusion. Transcripts down-regulated in responders 2 weeks after infliximab were related to innate immune signaling and nuclear factor-kappa B. Thus, baseline transcriptional signatures reflective of alterations in glucose and lipid metabolism predicted antidepressant selleck chemical response to infliximab, and infliximab response involved regulation of metabolic genes and inhibition of genes related to innate immune activation. (C) 2013 Elsevier Inc. All rights reserved.”
“Protein aggregation is of great concern to pharmaceutical formulations and has been implicated in several diseases. We engineered an anti-IL-13 monoclonal antibody CNTO607 for improved solubility. Three structure-based engineering approaches were employed in this study: (i) modifying the isoelectric point (pI), Selleckchem Momelotinib (ii) decreasing the overall surface hydrophobicity and (iii) re-introducing an N-linked carbohydrate moiety within a complementarity-determining
region (CDR) sequence. A mutant was identified with a modified pI that had a 2-fold improvement in solubility while retaining the binding affinity to IL-13. Several mutants with decreased overall surface hydrophobicity also showed moderately improved solubility while maintaining a similar antigen affinity. Structural studies combined with mutagenesis data identified an aggregation ‘hot spot’ in heavy-chain CDR3 (H-CDR3) that contains three residues ((99)FHW(100a)). The same residues, however, were found to be essential for high affinity binding to IL-13. On the basis of the spatial proximity and germline sequence, we reintroduced the consensus N-glycosylation site in H-CDR2 which was found in the original antibody, anticipating that the carbohydrate moiety would shield the aggregation ‘hot spot’ in H-CDR3 while not interfering with antigen binding.
4% were autonomic nerves. Furthermore, 23.9% of the nerve fibers innervating the IVD were afferent sensory pain-related nerves, 8.9% were efferent sympathetic nerves, and 11.5% were efferent parasympathetic nerves. These findings may explain the wide-ranging and chronic discogenic pain that occurs via the somatosensory and autonomic nervous system.”
“Purpose: to assess the predictive power of three systems: Infection Probability Score, APACHE II and KARNOFSKY score for the onset of Clostridium difficile-associated disease (CDAD) in hematology-oncology patients.\n\nMethods and sample: A retrospective pilot surveillance survey QNZ order was conducted in the hematology unit
of a general hospital in Greece. Data were collected JNK-IN-8 by using an anonymous standardised case-record form. The sample consisted of 102 hospitalized patients.\n\nResults: The majority of the patients (33.3%) suffered from acute myeloid leukemia. The cumulative incidence of CDAD was 10.8% and the incidence rate of C difficile associated diarrhea was 5 per 1000 patient-days (14.2 per 1000 patient-days at risk). Patients with CDAD had twofold higher time of mean length of hospital stay compared with patients without CDAD (38.82 +/- 23.88 vs 19.45 +/- 14.56 days). Additionally patients
with CDAD had received a greater number of different antibiotics compared to those without CDAD (5.18 +/- 1.99 vs 2.54 +/- 2.13), suffered from diabetes, from non Hodgkin’s lymphoma, had a statistically significant higher duration of neutropenia >= 3 days and had received antifungal treatment. The best cutoff Staurosporine value of IPS for the prediction of CDAD was 13 with a sensitivity of 45.5% and a specificity of 82.4%.\n\nConclusions: IPS is an early diagnostic
test for CDAD detection. (C) 2010 Elsevier Ltd. All rights reserved.”
“Selective fusion of thoracic and thoracolumbar/lumbar curves in adolescent idiopathic scoliosis is a concept critically debated in the literature. While some surgeons strongly believe that a more rigid and straighter spine provides predictably excellent outcomes, some surgeons recommend a mobile and less straight spine. This topic is a crucial part of surgical treatment of idiopathic scoliosis, particularly in young patients who will deal with the stress of the fusion mass at the proximal and distal junctions over many years. This study will review the literature on various aspects of selective fusion.”
“Background: EMR is an accepted treatment for early esophageal carcinoma. However, resection of a large mucosal area often causes postoperative esophageal stricture.\n\nObjective: To investigate the efficacy of autologous adipose tissue-derived stromal cells (ADSCs) for prevention of stricture formation after EMR in dogs.\n\nDesign: Animal study.\n\nSetting: University research center.\n\nIntervention: Ten beagle dogs were randomized into a control group and an ADSCs-injected (ADSC) group. The ADSCs were isolated from autologous adipose tissue.
Accordingly, MK-8776 ic50 inhibition of actin myosin interaction, Ca2+-dependent intracellular signaling,
PKC, PI3K/Akt, MAP kinase p38, and endocytosis pathways did not impair the chitosan effect. These results suggest that the rapid and reversible absorption-enhancing chitosan effect is due to changes in intracellular pH caused by the activation of a chloride-bicarbonate exchanger resulting in the opening of the TJ. (C) 2011 Elsevier Ltd. All rights reserved.”
“Thyroid dysfunction, however mild, can significantly affect the cardiovascular (CV) system. The effects of thyroid hormones may be viewed as genomic and non-genomic, with the former occurring over a longer time scale and both affecting structural and functional proteins in CV tissue. As the interplay between thyroid function and the CV selleck screening library system becomes elucidated, particularly in the context of a system biology approach, the heart failure phenotype is better understood. Symptomatology is related to disturbance in inotropic and chronotropic function. Moreover, biochemical changes reflected by thyroid function
testing with the non-thyroidal illness syndrome can prognosticate and guide therapy in heart failure. In addition, empiric treatment with thyroid hormone analogues or T3 represent emergent and highly controversial interventions. (C) 2009 Elsevier Masson SAS. All rights reserved.”
“A previous rotavirus epidemiological A-1210477 price survey in Cordoba, Argentina, revealed an unusually high frequency of mixed G-type infections (41.5%). The genotype distribution of those mixed infections showed that the most prevalent G-type combinations were G1 + G4 (65.0%), G1 + G2 (12.5%), G2 + G4 (3.1%) and G1 + G9 (2.5%). In the present study we analyzed the competitive growth in CaCo-2 cell cultures of strains from the most frequent rotavirus G-type coinfections in order to explain some aspect of the dynamic of G-type replacement along the time. Our results indicated
that G1-type was preferentially selected compared with G2 and G9-genotypes, meanwhile, G1-G4 coinfections showed an efficient co-amplification of both types. Interestingly, this mirrored the high detection rates of both genotypes as single and mixed infections (G1 + G4, 65.0%) in our region. On the other hand, G2-type revealed a better amplification rate with respect to G4-type. Fluctuant rates in the prevalence of different genotypes usually observed along the time could, in part, be explained by successive replacement of strains with different growth characteristics. We hypothesized that one aspect of these different fitnesses can be measured as differential growth in culture of the strains contained in the sample of a mixed infection. Our findings here provide the first data supporting the validity of the competitive replication in vitro to better understand rotavirus G-type circulation patterns. (C) 2008 Elsevier B.V. All rights reserved.
An M1 to M2 transition of tumor-associated macrophages was
demonstrated, paralleled by a deterioration of dendritic cell status. Treatment with low-dose aspirin to mice homozygous for the TH-MYCN transgene significantly reduced the tumor burden (P < 0.01), the presence of tumor-associated cells of the innate immune system (P < 0.01), as well as the intratumoral expression of transforming selleck chemicals growth factor-, thromboxane A(2) (P < 0.05) and prostaglandin D-2 (P < 0.01). In conclusion, tumor-associated inflammation appears as a potential therapeutic target in NB and low-dose aspirin reduces tumor burden in the TH-MYCN transgenic mouse model of NB, hence warranting further studies on aspirin in high-risk NB.”
“It was investigated whether continuous Fate infusion of the alpha(2)-adrenoceptor agonist dexmedetomidine can suppress memory
formation by mechanisms other than reducing perception of sensory input in a fear-conditioning paradigm. Different groups of rats infused with either saline or dexmedetomidine (2.0, 4.0 or 10.0 mu g/kg bolus, followed by 2.0, 4.0 or 10.0 mu g/kg/h continuous rate infusion respectively), were subjected to a somatosensory-evoked potential (SEP) fear-conditioning paradigm. This paradigm click here combined the pairing of an innoxious conditioned stimulus (CS) and a noxious unconditioned stimulus (US), of which the latter was used to generate the SEPs (training phase). The following day, the perception of the US during the training
phase was assessed by presenting the CS only and subsequently scoring the resulting duration of freezing behaviour (testing phase). Freezing behaviour was reduced only in those groups which demonstrated reduced SEPs. Based on these findings, it is concluded that dexmedetomidine suppresses memory formation only at doses reducing central nervous system activity in response to sensory input. (C) 2009 Elsevier B.V. All rights reserved.”
“Objectives This study sought to define contemporary trends in permanent pacemaker use by analyzing a large national database.\n\nBackground The Medicare National MLN4924 Coverage Determination for permanent pacemaker, which emphasized single-chamber pacing, has not changed significantly since 1985. We sought to define contemporary trends in permanent pacemaker use by analyzing a large national database.\n\nMethods We queried the Nationwide Inpatient Sample to identify permanent pacemaker implants between 1993 and 2009 using the International Classification of Diseases-Ninth Revision-Clinical Modification procedure codes for dual-chamber (DDD), single-ventricular (VVI), single-atrial (AAI), or biventricular (BiV) devices.
8% with method (i) and method (ii), respectively, and they resulted not statistically different (P> 0.05). Seroreactors (from 4.4 to 46%) were found in 7 of 9 tested flocks. Adult Echinococcus tapeworms were found in 2 of 4 necropsied dogs from 3 flocks. On the basis of the results, CE prevalence in small ruminants from Piedmont seems to be higher than that reported by official abattoir statistics in the last decade. (c) 2012 Elsevier B.V. All rights reserved.”
“For some phytophagous insects, egg maturation may be dependent on adult feeding. Accordingly, rates of egg maturation may be dependent
on the quality and quantity of available food sources. In turn, oviposition selleck behavior could be affected by diet quality via changes in egg load (number of mature eggs carried by a female). Experiments were conducted to determine whether adult feeding may affect oviposition Smoothened Agonist behavior of the glassy-winged sharpshooter,
Homalodisca vitripennis. No-choice tests demonstrated that eggs accumulated in glassy-winged sharpshooter abdomens as time since last oviposition increased largely as a function of feeding plant species. In choice tests, glassy-winged sharpshooter females were observed most frequently on the plant species that imparted the greatest egg maturation rate in no-choice tests. Direct tests of the effects of egg load on glassy-winged sharpshooter oviposition behavior found that females were more likely to deposit eggs as egg load increased. Similarly, acceptance of a low-ranked oviposition plant species by female glassy-winged sharpshooters increased with egg load and time since last oviposition. The results indicate that adult feeding affected glassy-winged sharpshooter egg maturation, plant species varied in quality for providing nutrients for egg maturation, and
egg load affected oviposition behavior. Thus, the quantity and quality of available feeding plant species may affect glassy-winged sharpshooter egg maturation rates, which in turn may affect the plant species female glassy-winged sharpshooters select for oviposition.”
“Background: Poor-quality life-saving medicines are a major public health threat, particularly in settings with a weak regulatory environment. Insufficient amounts of active pharmaceutical ingredients (API) endanger patient safety and may contribute to the development of drug Repotrectinib price resistance. In the case of malaria, concerns relate to implications for the efficacy of artemisinin-based combination therapies (ACT). In Papua New Guinea (PNG), Plasmodium falciparum and P. vivax are both endemic and health facilities are the main source of treatment. ACT has been introduced as first-line treatment but other drugs, such as primaquine for the treatment of P. vivax hypnozoites, are widely available. This study investigated the quality of antimalarial drugs and selected antibiotics at all levels of the health facility supply chain in PNG.