Miracle-dz/UniFAR-FTUs huggingface dataset:
Single Amino Acid Substitutions at Specific Positions of the Heptad Repeat Sequence of Piscidin-1 Yielded Novel Analogs That Show Low Cytotoxicity and In Vitro and In Vivo Antiendotoxin Activity

ABSTRACT Piscidin-1 possesses significant antimicrobial and cytotoxic activities. To recognize the primary amino acid sequence(s) in piscidin-1 that could be important for its biological activity, a long heptad repeat sequence located in the region from amino acids 2 to 19 was identified. To comprehend the possible role of this motif, six analogs of piscidin-1 were designed by selectively replacing a single isoleucine residue at a d (5th) position or at an a (9th or 16th) position with either an alanine or a valine residue. Two more analogs, namely, I5F,F6A-piscidin-1 and V12I-piscidin-1, were designed for investigating the effect of interchanging an alanine residue at a d position with an adjacent phenylalanine residue and replacing a valine residue with an isoleucine residue at another d position of the heptad repeat of piscidin-1, respectively. Single alanine-substituted analogs exhibited significantly reduced cytotoxicity against mammalian cells compared with that of piscidin-1 but appreciably retained the antibacterial and antiendotoxin activities of piscidin-1. All the single valine-substituted piscidin-1 analogs and I5F,F6A-piscidin-1 showed cytotoxicity greater than that of the corresponding alanine-substituted analogs, antibacterial activity marginally greater than or similar to that of the corresponding alanine-substituted analogs, and also antiendotoxin activity superior to that of the corresponding alanine-substituted analogs. Interestingly, among these peptides, V12I-piscidin-1 showed the highest cytotoxicity and antibacterial and antiendotoxin activities. Lipopolysaccharide (12 mg/kg of body weight)-treated mice, further treated with I16A-piscidin-1, the piscidin-1 analog with the highest therapeutic index, at a single dose of 1 or 2 mg/kg of body weight, showed 80 and 100% survival, respectively. Structural and functional characterization of these peptides revealed the basis of their biological activity and demonstrated that nontoxic piscidin-1 analogs with significant antimicrobial and antiendotoxin activities can be designed by incorporating single alanine substitutions in the piscidin-1 heptad repeat.
Influence of Reactive Oxygen Species on De Novo Acquisition of Resistance to Bactericidal Antibiotics

ABSTRACT The radical-based theory proposes that three major classes of bactericidal antibiotics, i.e., β-lactams, quinolones, and aminoglycosides, have in common the downstream formation of lethal levels of reactive oxygen species (ROS) as part of the killing mechanism. If bactericidal antibiotics exhibit a common mechanism, then it is to be expected that the acquisition of resistance against these drugs would have some shared traits as well. Indeed, cells made resistant to one bactericidal antibiotic more rapidly became resistant to another. This effect was absent after induced resistance to a bacteriostatic drug. De novo acquisition of resistance to one bactericidal antibiotic provided partial protection to killing by bactericidal antibiotics from a different class. This protective effect was observed in short-term experiments. No protective effect was detected during 24-h exposures, suggesting that cross-resistance did not occur. In the wild-type strain, exposure to bactericidal antibiotics increased intracellular ROS levels. This increase in ROS levels was not observed when strains resistant to these drugs were exposed to the same concentrations. These results indicate that de novo acquisition of resistance to the bactericidal drugs tested involves a common cellular response that provides protection against ROS accumulation upon exposure to this type of antibiotics. A central mechanism or at least a few common elements within the separate mechanisms possibly play a role during the acquisition of antibiotic resistance.
Pharmacokinetics and Pharmacodynamics of Minocycline against Acinetobacter baumannii in a Neutropenic Murine Pneumonia Model

ABSTRACT Multidrug-resistant (MDR) Acinetobacter baumannii is increasingly more prevalent in nosocomial infections. Although in vitro susceptibility of A. baumannii to minocycline is promising, the in vivo efficacy of minocycline has not been well established. In this study, the in vivo activity of minocycline was evaluated in a neutropenic murine pneumonia model. Specifically, we investigated the relationship between minocycline exposure and bactericidal activity using five A. baumannii isolates with a broad range of susceptibility (MIC ranged from 0.25 mg/liter to 16 mg/liter). The pharmacokinetics of minocycline (single dose of 25 mg/kg of body weight, 50 mg/kg, 100 mg/kg, and a humanized regimen, given intraperitoneally) in serum and epithelial lining fluid (ELF) were characterized. Dose linearity was observed for doses up to 50 mg/kg and pulmonary penetration ratios (area under the concentration-time curve in ELF from 0 to 24 h [AUCELF,0–24]/area under the concentration time curve in serum from 0 to 24 h [AUCserum,0–24]) ranged from 2.5 to 2.8. Pharmacokinetic-pharmacodynamics (PK-PD) index values in ELF for various dose regimens against different A. baumannii isolates were calculated. The maximum efficacy at 24 h was approximately 1.5-log-unit reduction of pulmonary bacterial burdens from baseline. The AUC/MIC ratio was the PK-PD index most closely correlating to the bacterial burden (r2 = 0.81). The required AUCELF,0–24/MIC for maintaining stasis and achieving 1-log-unit reduction were 140 and 410, respectively. These findings could guide the treatment of infections caused by A. baumannii using minocycline in the future. Additional studies to examine resistance development during therapy are warranted.
The Pathology of Acute Yellow Atrophy and Delayed Chloroform Poisoning

THE literature contains a number of cases reported under the title of acute yellow atrophy of the liver in pregnancy. Many of these may be discarded from the present consideration, since the diagnosis was based only on, clinical grounds or on post-mortem examination without any histology. An analysis of the cases in which investigation was adequate reveals a variety of different conditions which may be discussed in three main categories: true acute yellow atrophy, obstetric acute yellow atrophy, and delayed chloroform poisoning. In the discussion of delayed chloroform poisoning, consideration will be given not only to the cases reported as acute yellow atrophy but also to the other aspects of this subject as met with in obstetrics.
Chewing Patterns in Subjects with Normal Occlusion and With Malocclusions

This report describes the chewing patterns of individuals with normal occlusion and several types of malocclusion. Frontal movement patterns of the lower mid-incisor point were recorded during chewing of test foods in groups of subjects with Angle Class I normal occlusion, Class II malocclusion, as well as deep-bite and cross-bite malocclusions. Mandibular prognathic and retrognathic patients corrected to Angle Class I occlusions were also examined before and after orthognathic surgery. Chewing patterns were classified by using a catalogue of eight basic movement types. In none of the groups examined could chewing behavior be characterized by only one specific type of movement, but rather by different frequency distributions of pattern types. The Angle Class I, Class II, deep-bite, and presurgical retrognathism groups were characterized by chewing patterns with normal sequencing and grinding features and, to a minor extent, by self-crossing movements having no unique pattern of sequencing. Reversed sequencing did not occur in these four groups. In presurgical prognathic patients, drop-shaped patterns with steep closing movements predominated. Cross-bite malocclusion was characterized by drop-shaped and reversed sequencing patterns. The pattern distribution in prognathic patients did not change after surgery. In retrognathic patients the therapeutically altered occlusion caused a decrease in the frequency of grinding movements and an increase in the frequency of drop-shaped patterns.
Changes in self-rated health and subjective social status over time in a cohort of healthcare personnel

As part of a prospective cohort study of 1354 female and 347 male healthcare personnel, we examined the stability of subjective social status over ~7 months and the prospective association between subjective social status and self-rated health status. Most (82%) subjective social status ratings were stable (within ±1 point). Lower baseline subjective social status among healthcare personnel was associated with more subsequent reports of fatigue and headache and worsening global self-rated health status. Healthcare personnel who placed themselves on the bottom half of the subjective social status ladder were four times more likely to experience a decline in global self-rated health status and half as likely to improve to excellent self-rated health status.
CYP2B6 18492T→C Polymorphism Compromises Efavirenz Concentration in Coinfected HIV and Tuberculosis Patients Carrying CYP2B6 Haplotype *1/*1

ABSTRACT Data regarding the effect of the CYP2B6 18492T→C polymorphism on plasma efavirenz concentrations and 96-week virologic responses in patients coinfected with HIV and tuberculosis (TB) are still unavailable. A total of 139 antiretroviral-naive HIV-infected adults with active TB were prospectively enrolled to receive efavirenz 600 mg-tenofovir 300 mg-lamivudine 300 mg. Eight single nucleotide polymorphisms (SNPs) within CYP2B6 were genotyped. Seven SNPs, including 64C→T, 499C→G, 516G→T, 785A→G, 1375A→G, 1459C→T, and 21563C→T, were included for CYP2B6 haplotype determination. The CYP2B6 18492T→C polymorphism was studied in 48 patients who carried haplotype *1/*1. At 12 and 24 weeks after antiretroviral therapy, plasma efavirenz concentrations at 12 h after dosing were measured. Plasma HIV RNA was monitored every 12 weeks for 96 weeks. Of 48 patients {body weight [mean ± standard deviation (SD)], 56 ± 10 kg}, 77% received a rifampin-containing anti-TB regimen. No drug resistance-associated mutation was detected at baseline. The frequencies of the wild type (18492TT) and the heterozygous (18492TC) and homozygous (18492CC) mutants of the CYP2B6 18492T→C polymorphism were 39%, 42%, and 19%, respectively. At 12 weeks, mean (±SD) efavirenz concentrations of patients who carried the 18492TT, 18492TC, and 18492CC mutants were 2.8 ± 1.6, 1.7 ± 0.9, and 1.4 ± 0.5 mg/liter, respectively (P = 0.005). At 24 weeks, the efavirenz concentrations of the corresponding groups were 2.4 ± 0.8, 1.7 ± 0.8, and 1.2 ± 0.4 mg/liter, respectively (P = 0.003). A low efavirenz concentration was independently associated with 18492T→C (β = −0.937, P = 0.004) and high body weight (β = −0.032, P = 0.046). At 96 weeks, 19%, 17%, and 28% of patients carrying the 18492TT, 18492TC, and 18492CC mutants, respectively, had plasma HIV RNA levels of >40 copies/ml and developed efavirenz-associated mutations (P = 0.254). In summary, the CYP2B6 18492T→C polymorphism compromises efavirenz concentrations in patients who carry CYP2B6 haplotype *1/*1 and are coinfected with HIV and tuberculosis.
Epidemiology of Antituberculosis Drug Resistance in Saudi Arabia: Findings of the First National Survey

ABSTRACT The real magnitude of antituberculosis (anti-TB) drug resistance in Saudi Arabia is still unknown because the available data are based on retrospective laboratory studies that were limited to hospitals or cities. A representative national survey was therefore conducted to investigate the levels and patterns of anti-TB drug resistance and explore risk factors. Between August 2009 and July 2010, all culture-positive TB patients diagnosed in any of the tuberculosis reference laboratories of the country were enrolled. Isolates obtained from each patient were tested for susceptibility to first-line anti-TB drugs by the automated Bactec MGIT 960 method. Of the 2,235 patients enrolled, 75 cases (3.4%) were lost due to culture contamination and 256 (11.5%) yielded nontuberculous mycobacteria (NTM). Finally, 1,904 patients (85.2% of those enrolled) had available drug susceptibility testing results. Monoresistance to streptomycin (8.1%; 95% confidence interval [CI], 7.2 to 9.1), isoniazid (5.4%; 95% CI, 4.7 to 6.2), rifampin (1%; 95% CI, 0.7 to 1.3) and ethambutol (0.8%; 95% CI, 0.5 to 1.2) were observed. Multidrug-resistant TB (MDR-TB) was found in 1.8% (95% CI, 1.4 to 2.4) and 15.9% (95% CI, 15.4 to 16.5) of new and previously treated TB cases, respectively. A treatment history of active TB, being foreign-born, having pulmonary TB, and living in the Western part of the country were the strongest independent predictors of MDR-TB. Results from the first representative national anti-TB drug resistance survey in Saudi Arabia suggest that the proportion of MDR-TB is relatively low, though there is a higher primary drug resistance. A strengthened continuous surveillance system to monitor trends over time and second-line anti-TB drug resistance as well as implementation of innovative control measures, particularly among immigrants, is warranted.
Evaluating the Impact of a National AIDS Prevention Radio Campaign in St. Vincent and the Grenadines1

To assess the impact of a mass media campaign conducted in St Vincent and the Grenadines with the aim of promoting condom use to prevent acquired immunodeficiency syndrome (AIDS) a follow-up survey was conducted six weeks after the campaigns completion. The two-month radio campaign was primarily directed toward the parents of teenagers. Included in the follow-up survey were 100 teenagers 100 parents of teens and 100 other persons selected through a national quota sampling plan. The 213 (71.6%) respondents who reported exposure to radio advertisements about condoms or AIDS in the preceding five months and could give an accurate description of their content were classified as "exposed" to the campaign; the remaining 84 (28.4%) were considered "nonexposed. " Exposed subjects had greater access to radio and television; otherwise the two groups were similar. A significantly greater proportion of those exposed to the campaign (97.7%) believed people can protect themselves from the AIDS virus than nonexposed controls (86.2%). Moreover 38.7% of exposed parents of teens compared to 26.4% of nonexposed parents had talked to their child about condoms. On the other hand there were no significant differences between groups in terms of agreement that condoms protect against AIDS the perception that condom purchase is embarrassing or intent to use condoms at next intercourse. Overall however the mass media campaign appears to have succeeded in increasing AIDS awareness.
RAAC: Robust and Auditable Access Control With Multiple Attribute Authorities for Public Cloud Storage

Data access control is a challenging issue in public cloud storage systems. Ciphertext-policy attribute-based encryption (CP-ABE) has been adopted as a promising technique to provide flexible, fine-grained, and secure data access control for cloud storage with honest-but-curious cloud servers. However, in the existing CP-ABE schemes, the single attribute authority must execute the time-consuming user legitimacy verification and secret key distribution, and hence, it results in a single-point performance bottleneck when a CP-ABE scheme is adopted in a large-scale cloud storage system. Users may be stuck in the waiting queue for a long period to obtain their secret keys, thereby resulting in low efficiency of the system. Although multi-authority access control schemes have been proposed, these schemes still cannot overcome the drawbacks of single-point bottleneck and low efficiency, due to the fact that each of the authorities still independently manages a disjoint attribute set. In this paper, we propose a novel heterogeneous framework to remove the problem of single-point performance bottleneck and provide a more efficient access control scheme with an auditing mechanism. Our framework employs multiple attribute authorities to share the load of user legitimacy verification. Meanwhile, in our scheme, a central authority is introduced to generate secret keys for legitimacy verified users. Unlike other multi-authority access control schemes, each of the authorities in our scheme manages the whole attribute set individually. To enhance security, we also propose an auditing mechanism to detect which attribute authority has incorrectly or maliciously performed the legitimacy verification procedure. Analysis shows that our system not only guarantees the security requirements but also makes great performance improvement on key generation.
Fetal Transverse Cerebellar Diameter Measurement for Prediction of Gestational Age in Pregnant Sudanese Ladies

This study was carried out to evaluate whether Transverse Cerebellar Diameter (TCD) in singleton gestations can serve as a reliable predictor of gestational age (GA) in fetuses in the second and third trimester of pregnancy. A prospective study was carried out with 50 pregnant ladies, GA ranging from 15to37 weeks (estimation of mean GA was 26.8 ± 6.8 weeks), with a single fetus.TCD measurement by ultrasound was used for each fetus. Correlations between fetal TCD and GA were determined for the whole sample. Mean TCD was 28.6 ± 7.5 mm in 15-37 weeks of gestation. Regression analysis indicates a significant relationship between TCD and GA; correlation coefficient (r) = 0.94 and p< 0.001. Fetal TCD by ultrasound could be a predictive biometric parameter of GA in the last two trimesters of a pregnancy. Keywords-Fetal Transverse Cerebellar Diameter (TCD); Gestational age (GA); Ultrasound
Privacy-Preserving Smart Semantic Search Based on Conceptual Graphs Over Encrypted Outsourced Data

Searchable encryption is an important research area in cloud computing. However, most existing efficient and reliable ciphertext search schemes are based on keywords or shallow semantic parsing, which are not smart enough to meet with users’ search intention. Therefore, in this paper, we propose a content-aware search scheme, which can make semantic search more smart. First, we introduce conceptual graphs (CGs) as a knowledge representation tool. Then, we present our two schemes (PRSCG and PRSCG-TF) based on CGs according to different scenarios. In order to conduct numerical calculation, we transfer original CGs into their linear form with some modification and map them to numerical vectors. Second, we employ the technology of multi-keyword ranked search over encrypted cloud data as the basis against two threat models and raise PRSCG and PRSCG-TF to resolve the problem of privacy-preserving smart semantic search based on CGs. Finally, we choose a real-world data set: CNN data set to test our scheme. We also analyze the privacy and efficiency of proposed schemes in detail. The experiment results show that our proposed schemes are efficient.
Impact of Primary Elvitegravir Resistance-Associated Mutations in HIV-1 Integrase on Drug Susceptibility and Viral Replication Fitness

ABSTRACT Elvitegravir (EVG) is an effective HIV-1 integrase (IN) strand transfer inhibitor (INSTI) in advanced clinical development. Primary INSTI resistance-associated mutations (RAMs) at six IN positions have been identified in HIV-1-infected patients failing EVG-containing regimens in clinical studies: T66I/A/K, E92Q/G, T97A, S147G, Q148R/H/K, and N155H. In this study, the effect of these primary IN mutations, alone and in combination, on susceptibility to the INSTIs EVG, raltegravir (RAL), and dolutegravir (DTG); IN enzyme activities; and viral replication fitness was characterized. Recombinant viruses containing the six most common mutations exhibited a range of reduced EVG susceptibility: 92-fold for Q148R, 30-fold for N155H, 26-fold for E92Q, 10-fold for T66I, 4-fold for S147G, and 2-fold for T97A. Less commonly observed primary IN mutations also showed a range of reduced EVG susceptibilities: 40- to 94-fold for T66K and Q148K and 5- to 10-fold for T66A, E92G, and Q148H. Some primary IN mutations exhibited broad cross-resistance between EVG and RAL (T66K, E92Q, Q148R/H/K, and N155H), while others retained susceptibility to RAL (T66I/A, E92G, T97A, and S147G). Dual combinations of primary IN mutations further reduced INSTI susceptibility, replication capacity, and viral fitness relative to either mutation alone. Susceptibility to DTG was retained by single primary IN mutations but reduced by dual mutation combinations with Q148R. Primary EVG RAMs also diminished IN enzymatic activities, concordant with their structural proximity to the active site. Greater reductions in viral fitness of dual mutation combinations may explain why some primary INSTI RAMs do not readily coexist on the same HIV-1 genome but rather establish independent pathways of resistance to EVG.
Investigation of association between indoor environmental factors and child health problems in Japan – Design of survey and outcome from preliminary cross-sectional questionnaire

In Japan, there is an increase in allergic diseases such as asthma, respiratory symptom, particularly prevailing among the young generation. The reasons why the prevalence is increasing are still not yet well understood. However, it is deemed that indoor environmental factors are one of the essential sources. Therefore, an epidemiology type of survey was investigated on the 4th and 5th grade school children in Japan. The survey was divided into three phases. Phase 1 was a preliminary cross-sectional questionnaire of the prevalence of health problems. Phase 2 was a cross-sectional questionnaire survey on housing characteristics and health. Phase 3 was a field measurement for case control. This paper describes the study protocol and the outcomes from Phase 1. The prevalence of current allergic symptoms was 49.9%. Asthma and rhinitis of the children were 12.5% and 33.3%, respectively. The prevalence of several allergic symptoms among boys was significantly higher than in girls. It indicated that the environmental factors such as pollen, indoor house dust and dust mites could influence allergic symptoms. This survey reveals the ratio of children allergic symptoms in Japan and the possibility of the association between adverse health effect and indoor environmental factors.
The relationship between nature relatedness and anxiety

This study investigated the relationship between anxiety and feelings of being connected to nature. Two standardised self-report scales, the Nature Relatedness Scale and the State Trait Inventory for Cognitive and Somatic Anxiety, were used in tandem with a qualitative question. Quantitative results indicated that connection to nature was significantly related to lower levels of overall, state cognitive and trait cognitive anxiety. Qualitative results revealed seven themes: relaxation, time out, enjoyment, connection, expanse, sensory engagement and a healthy perspective. Taken together, these results suggest that opportunities that enhance experiences of being connected to nature may reduce unhelpful anxiety.