External validation of a 2-year all-cause mortality prediction tool developed using machine learning in patients with stage 4-5 chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased mortality. Individual mortality prediction could be of interest to improve individual clinical outcomes. Using an independent regional dataset, the aim of the present study was to externally validate the recently published 2-year all-cause mortality prediction tool developed using machine learning. METHODS: A validation dataset of stage 4 or 5 CKD outpatients was used. External validation performance of the prediction tool at the optimal cutoff-point was assessed by the area under the receiver operating characteristic curve (AUC-ROC), accuracy, sensitivity, and specificity. A survival analysis was then performed using the Kaplan-Meier method. RESULTS: Data of 527 outpatients with stage 4 or 5 CKD were analyzed. During the 2 years of follow-up, 91 patients died and 436 survived. Compared to the learning dataset, patients in the validation dataset were significantly younger, and the ratio of deceased patients in the validation dataset was significantly lower. The performance of the prediction tool at the optimal cutoff-point was: AUC-ROC = 0.72, accuracy = 63.6%, sensitivity = 72.5%, and specificity = 61.7%. The survival curves of the predicted survived and the predicted deceased groups were significantly different (p < 0.001). CONCLUSION: The 2-year all-cause mortality prediction tool for patients with stage 4 or 5 CKD showed satisfactory discriminatory capacity with emphasis on sensitivity. The proposed prediction tool appears to be of clinical interest for further development.

Antibiofilm Action of ZnO, SnO2 and CeO2 Nanoparticles Towards Grampositive Biofilm Forming Pathogenic Bacteria.

BACKGROUND: The ability to form biofilm and produce several virulence factors has caused numerous human pathogens to become tremendously resistant towards traditional antibiotic treatments, thus, new alternative strategies are urgently in demand. One of the strategies that have recently been developed involves the application of metallic Nanoparticles (NPs). Up to the present, promising results in terms of antimicrobial and antibiofilm activities have been observed in a wide range of metal NPs. METHODS: The present study has selected three metal oxides such as ZnO, SnO2 and CeO2 NPs to comparatively investigate their antibiofilm and antibacterial properties against two Gram-positive human pathogens, which are Listeria monocytogenes and Staphylococcus aureus. RESULTS: The anti-biofilm activities of ZnO, SnO2 and CeO2 NPs against S. aureus and L. monocytogenes were assayed by crystal violet staining and confirmed by microscopic visualization using SEM. The synthesis of amyloid protein by S. aureus and exopolysaccharide by L. monocytogenes in the presence of ZnO, SnO2 and CeO2 NPs was evaluated by Congo red assay. DISCUSSION: Results have shown that ZnO, SnO2 and CeO2 NPs effectively inhibited biofilm formation of both L. monocytogenes and S. aureus. The microscopic analysis also confirmed the antibiofilm activity of these NPs. It was also found that only ZnO NPs inhibited cell growth as well as the production of amyloid protein in S. aureus. CONCLUSION: Overall, these results indicated that ZnO, SnO2 and CeO2 NPs can be considered as potential agents for treating the infections caused by L. monocytogenes and S. aureus, especially those associated with biofilm formation. Based on the present study, further studies are required to understand their mechanisms at both phenotypic and molecular levels, as well as their in vivo cytotoxicity, thereby enabling the applications of these metal oxide NPs in biomedical fields and food industry.

Absence or mislocalization of DNAH5 is a characteristic marker for motile ciliary abnormality in nasal polyps.

OBJECTIVE: Motile cilia impairment is a common condition in patients with chronically inflamed airways, such as is seen in nasal polyps (NPs). The mechanism underlying this pathogenic condition is complex and not fully understood. METHODS: We investigated the presence and localization of dynein axonemal heavy chain 5 (DNAH5) in motile cilia using immunofluorescence staining in paraffin-embedded nasal biopsies from NPs (n = 120) and inferior turbinate mucosa (n = 35) of healthy controls. We also performed single-cell staining on cytospin samples (NP = 5, control = 5). Three patterns of DNAH5 localization are defined, including pattern A (presence throughout the axoneme), pattern B (undetectable in the distal part of the axoneme), and pattern C (completely missing throughout the entire axoneme). We developed a semiquantitative scoring system for which 0 = (pattern A > 70%); 1 = (patterns A + B > 70%); and 2 = (pattern C ≥ 30%) in each high-power field (5 fields per sample). RESULTS: Based on our DNAH5 scoring system, the median (1st and 3rd quartile) score was 0.3 (0.2 and 0.4) for samples from controls, and 1.1 (0.6 and 1.6) for samples from NPs in paraffin specimens (P < 0.001). The DNAH5 score had a significant positive relationship with the Lund-Mackay computed tomography score (r = 0.329, P = 0.005) and was higher in patients with eosinophilic NPs (P = 0.006). For cytospin samples, the mean percentage of patterns A, B, and C were 74%, 14%, and 12% in controls, and 48%, 20%, and 32% in NPs, respectively. CONCLUSION: Our results suggest that the absence or mislocalization of DNAH5 from motile cilia is a common and potentially important pathological phenomenon in chronically inflamed airway epithelium. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E97-E104, 2018.

Chronic hepatitis C infection and liver disease in HIV-coinfected patients in Asia.

Data on markers of hepatitis C virus (HCV) disease in HIV-HCV-coinfected patients in resource-limited settings are scarce. We assessed HCV RNA, HCV genotype (GT), IL28B GT and liver fibrosis (FibroScan® ) in 480 HIV-infected patients with positive HCV antibody in four HIV treatment centres in South-East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median (IQR) age was 38.1 (34.7-42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median (IQR) CD4 count was 446 (325-614) cells/mm3 and 208 (94.1%) of 221 patients tested had HIV-1 RNA <400 copies/mL. A total of 412 (85.8%) had detectable HCV RNA, at a median (IQR) of 6.2 (5.4-6.6) log10 IU/mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, eight (2.1%) had GT4, two (0.5%) had GT2, and seven (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan® , 143 (37.6%) had no/mild liver fibrosis (F0-F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan® failure. In conclusion, a high proportion of HIV-HCV-coinfected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (≥F2).

Increase of poorly proliferated p63+ /Ki67+ basal cells forming multiple layers in the aberrant remodeled epithelium in nasal polyps.

BACKGROUND: Aberrant epithelial remodeling with the ectopic expression of p63 (basal cell markers) is an important pathologic phenomenon seen in chronically inflamed airway epithelium such as in nasal polyps (NPs). METHODS: Biopsies were obtained from 55 NP patients and 18 healthy controls (inferior turbinate). Among NP patients, 15 were treated with oral and nasal steroids, so that two sets of NP biopsies were taken before and after the treatments. p63, Ki67, type IV ß-tubulin, and cell cycle markers were investigated in these specimens. RESULTS: The number of p63+ cells is significantly higher in both hyperplastic (1.53-fold, P < 0.0001) and squamous metaplastic (2.02-fold, P < 0.0001) epithelium from NPs than from healthy controls. There are three types of proliferative basal cells (p63+ /Ki67+ ) which are in different phases of the cell cycle, such as G1 phase (type I cells), S to G2 phase (type II cells), and mitosis (type III cells). Of importance, some type I cells may arrest after proliferation although they may still be p63+ /Ki67+ . In healthy epithelium, the ratio of the type I and II cells is almost 50:50. However, less type II cells are found in hyperplastic epithelium (34.85%, P = 0.012) and in squamous metaplastic epithelium (30.77%, P = 0.02) together with the presence of type III cells (3.45%, P = 0.01). These findings were not changed after steroid treatments. CONCLUSIONS: An increase of poorly proliferated basal cells forming multiple layers, which may stain for basal cell markers but does not form a proper epidermal barrier, is an important histopathologic phenomenon in aberrant remodeled epithelium of NPs.

Implementation of GINA guidelines in Ho Chi Minh City: a model for Viet Nam.

SETTING: The Global Initiative for Asthma (GINA) guidelines have not been implemented effectively in primary care settings in Viet Nam. OBJECTIVES: To estimate the proportion of patients with controlled asthma and the direct health care costs of managing asthma according to GINA guidelines at four out-patient clinics in Ho Chi Minh City (HCMC), Viet Nam. METHODS: One hundred and six patients with asthma were treated and followed up according to GINA guidelines for 12 months. Clinical and pulmonary function responses and direct health care costs were evaluated every 3 months during the study. RESULTS: The proportion of patients with controlled asthma rose from 1.0% at the start of the study to 36.8% by the end of the study (P < 0.0001). The proportion of patients who had at least one hospitalisation per year decreased significantly, from 32.1% to 5.7% (P < 0.0001). The annual per patient median direct health care cost was US$169. Using asthma controllers continuously gave better asthma control than using them intermittently (OR 12.9, 95%CI 4.7-35.7). CONCLUSIONS: The implementation of GINA guidelines at out-patient clinics in HCMC, Viet Nam, improved asthma control with modest direct health care costs.

In vitro inhibition of food spoilage and foodborne pathogenic bacteria by essential oil and leaf extracts of Magnolia liliflora Desr.

The aim of this study was to examine the chemical composition of the essential oil isolated from the floral parts of Magnolia liliflora Desr. by hydrodistillation, and to test the efficacy of essential oil and various leaf extracts against a diverse range of microorganisms comprising food spoilage and foodborne pathogenic bacteria. The chemical composition of essential oil was analyzed by GC-MS. It was determined that 52 compounds, which represented 78.07% of total oil, were present in the oil. The oil contained mainly levoxine (15.59%), methylcyclopropane (24.26%), 2-beta-pinene (5.3%), caryophyllene oxide (4.01%), and beta-caryophyllene (1.7%). The oil (1000 ppm/disc) and leaf extracts (1500 ppm/disc) exhibited promising antibacterial effects against the tested pathogens as a diameter of zones of inhibition (9 to 18 and 7 to 12 mm) and MIC values (125 to 1000 and 500 to 3000 microg/mL), respectively. Also, the oil had a potent detrimental effect on the viable count of the tested bacteria. The results obtained in this study support the role of essential oil and the leaf extracts derived from M. liliflora as a remarkable approach to inhibit the growth of food spoilage and foodborne pathogens.

Functionality of selected strains of moulds and yeasts from Vietnamese rice wine starters.

The role of starch-degrading mycelial fungi, and the alcohol production and ethanol tolerance of the yeasts isolated from selected Vietnamese traditional rice wine starters were examined, and optimum conditions for these essential steps in rice wine fermentation were determined. Of pure isolates from Vietnamese rice wine starters, mould strains identified as Amylomyces rouxii, Amylomyces aff. rouxii, Rhizopus oligosporus and Rhizopus oryzae, were superior in starch degradation, glucose production and amyloglucosidase activity during the saccharification of purple glutinous rice. A. rouxii was able to produce up to 25%w/w glucose with an amyloglucosidase activity up to 0.6 Ug(-1) of fermented moulded mass. Five yeast isolates identified as Saccharomyces cerevisiae were selected for their superior alcohol productivity. They were able to deplete a relatively high initial percentage of glucose (20% w/v), forming 8.8% w/v ethanol. The ethanol tolerance of S. cerevisiae in challenge tests was 9-10% w/v, and 13.4% w/v as measured in fed-batch fermentations. Optimum conditions for the saccharification were: incubation for 2 d at 34 degrees C, of steamed rice inoculated with 5 log cfu g(-1); for the alcoholic fermentation 4 d at 28.3 degrees C, of saccharified rice liquid inoculated with 5.5 log cfu mL(-1).

The effect of Trypanosoma evansi infection on pig performance and vaccination against classical swine fever.

Although Trypanosoma evansi is not considered as an important pathogen in pigs, it may interfere with other pathogens or vaccinations by its immunosuppressive nature. In order to determine whether T. evansi alters pig performance and induces immunosuppression in pigs, induction of immune responses by vaccination against classical swine fever (CSF) and by immunization with a control antigen, human serum albumin (HSA), was assessed in T. evansi-infected and non-infected animals. Although T. evansi infection did not have a significant influence on growth performance, feed conversion or PCV, antibody responses against both the test antigen HSA and the CSF vaccine were significantly reduced in T. evansi-infected animals as compared to uninfected animals. Moreover, the reduced response against the CSF vaccine appears to be accompanied by a less well-developed protection against CSF with higher fever responses and leukopenia. This immunosuppression might explain the accounts of poor protection of CSF-vaccinated pigs reported in T. evansi-endemic areas of Vietnam, and suggests that prior treatments with trypanocidal drugs to improve the efficacy of CSF vaccination, may be justified.

First cases of disseminated penicilliosis marneffei infection among patients with acquired immunodeficiency syndrome in Vietnam.

To our knowledge, this is the first report of penicilliosis marneffei among patients with acquired immunodeficiency syndrome (AIDS) in Vietnam. The 4 patients we studied were from Ho Chi Minh City and the provinces of Tay Ninh, Dong Nai, and Kon Tum. In 2 patients, the infections were fatal.

Management of multiple drug-resistant malaria in Viet Nam.

Malaria is still the most common infectious cause of mortality and morbidity in Viet Nam as it is in many developing countries in the tropics. The presence of resistance to available antimalarials and compliance in the target population are factors that influence the choice of drugs and regimens. In order to develop an ideal treatment for malaria, we conducted several clinical trials in patients with the disease in different settings. The results of these trials suggest that a combination of single dose artemisinin (or its derivatives) and mefloquine is the most effective, safe and practical treatment for acute non-complicated malaria due to multidrug-resistant Plasmodium falciparum. Concerning severe and complicated malaria, parenteral or rectal multi-doses of artemisinin or analogues are recommended due to their rapid parasite clearance time and other possible anti-cytoadherence effects. With its rapid parasite clearance, very early treatment of uncomplicated cases with artemisinin (and derivatives), especially at a health post level may help to prevent the development of complications, consequently reducing the number of severe cases and the malaria mortality rate.

An open randomized comparison of intravenous and intramuscular artesunate in severe falciparum malaria.

An open paired randomized comparison of intramuscular and intravenous artesunate was conducted in 28 adult patients with severe falciparum malaria. The dose regimen in both groups was 2 mg/kg given immediately followed by 1 mg/kg at 12 and 24 h, and then daily until the patient could swallow. Both routes of administration were well tolerated and there was no evidence of toxicity. One patient in each treatment group died. Clinical and parasitological measures of recovery in survivors were similar in the 2 groups with mean fever clearance times of 37.3 h (standard deviation [SD] = 26.1 h) and 31.5 h (SD = 24.2 h) and mean parasite clearance times of 33.4 h (SD = 13.9 h) and 29.4 h (SD = 12.7 h) in the intravenous and intramuscular groups respectively. Artesunate is equally effective and well tolerated when given by the intravenous or intramuscular routes.

Effects of adrenaline pretreatment on in vitro binding of 125I-triiodothyronine to nuclear receptor, intracellular distribution of endogenous triiodothyronine and activities of alfa-glycerophosphate dehydrogenase and malic enzyme in rat liver.

Especially coated adrenaline tablets (A) or placebo tablets (P) which release linearly the hormone were implanted in male Wistar rats. Six hours later animals were sacrificed and kinetic parameters of T3-125I binding to nuclear receptor, intracellular distribution of endogenous T3 and activities of alfa-GPD and ME were investigated. The association constant values (Ka) of nuclear receptor were increased after pretreatment with 7.5, 15 and 45 mg A tablets and were 1.07, 1.35 and 1.48 X 10(9) M-1 vs 0.85 X 10(8) M-1 value seen after P. The maximal binding capacity (MBC) values decreased after pretreatment with the same doses of A and were 0.044, 0.036 and 0.025 pmol T3/100 micrograms DNA vs. 0.065 pmol T3/100 micrograms DNA in P pretreated. Adrenaline pretreatment significantly increased the amount of endogenous T3 present in liver nuclei while the amount of T3 present in cytosol decreased. Activity of mitochondrial alfa-GPD was increased after 15 and 45 mg of A. Significant rise of activity of cytosol ME was seen only after pretreatment with 45 mg of A.