Miracle-dz/UniFAR-FTUs huggingface dataset:
Lack of a clinically important pharmacokinetic interaction between sofosbuvir or ledipasvir and hormonal oral contraceptives norgestimate/ethinyl estradiol in HCV‐Uninfected female subjects

This study evaluated the potential for a drug–drug interaction between HCV direct‐acting antivirals sofosbuvir or ledipasvir and oral hormonal contraceptive (OC) norgestimate/ethinyl estradiol (norgestimate 0.18/0.215/0.25 mg with ethinyl estradiol 25 μg). This was a 112‐day, open‐label, fixed‐sequence pharmacokinetic (PK) study in healthy female subjects that included a lead‐in cycle (OC only; N = 21), cycle 1 (OC only; N = 15), cycle 2 (OC + sofosbuvir; N = 15), and cycle 3 (OC + ledipasvir; N = 15). Administration of sofosbuvir with OC did not alter PK of norelgestromin (primary norgestimate metabolite) or ethinyl estradiol. Small increases in norgestrel (secondary norgestimate metabolite) AUCtau (19%) and Ctau (23%) with sofosbuvir were noted. Ledipasvir did not impact PK of norelgestromin or norgestrel but modestly increased ethinyl estradiol Cmax (40%). Sofosbuvir, GS‐ 331007 (predominant circulating metabolite of SOF), and ledipasvir PK were similar to historical data. Pharmacodynamic markers luteinizing hormone, follicle‐stimulating hormone, and progesterone values were generally comparable in all cycles. No loss in contraceptive efficacy is expected upon administration of sofosbuvir or ledipasvir/sofosbuvir with oral contraceptives containing norgestimate and ethinyl estradiol. The use of sofosbuvir or ledipasvir/sofosbuvir FDC with oral contraceptives is permitted.
Risk of Discontinuation of Nevirapine due to Toxicities in Antiretroviral-Naive and -Experienced HIV-Infected Patients with High and Low CD4+ T-Cell Counts

INTRODUCTION It is unknown whether the increased risk of toxicities in antiretroviral-naive HIV-infected patients initiating nevirapine-based (NVPc) combination antiretroviral therapy (cART) with high CD4+ T-cell counts is also observed when NVPc is initiated in cARTexperienced patients. PATIENTS AND METHODS 1,571 EuroSIDA patients started NVPc after 1/1/1999, with CD4+ T-cell counts and viral load measured in the 6 months before starting treatment, and were stratified into four groups based on CD4+ T-cell counts at initiation of NVPc (high [H], > 400/mm3 or > 250/mm3 for male or female, respectively, or low [L], < or = 400/mm3 or 5250/mm3 for male or female) and prior antiretroviral experience (antiretroviral-naive [N] or -experienced [E]). Cox proportional hazards models compared the risks of discontinuation of nevirapine due to toxicities or patient/physician choice (TOXPC). RESULTS After adjustment, there was a significantly lower risk of discontinuation of nevirapine due to TOXPC in the HE group (n = 588; proportion discontinued by 3/12 months: 10/17%, respectively) than in HN (n = 62; 21/32% respectively; overall relative hazard [RH]: 0.56; 95% confidence interval [CI]: 0.34-0.94; P = 0.027). This difference was most pronounced during the first 3 months of NVPc (RH: 0.44; 95% CI: 0.23-0.87; P = 0.017). There were no deaths in the 6 months after starting NVPc resulting from exposure to < 3 months of NVPc exposure within the HE group (incidence: 0; per 1,000 person-years follow up; 95% CI: 0-6.9). After adjustment, there were no differences between the HE and HN groups in discontinuation due to TOXPC in patients starting efavirenz-based cART (RH: 0.91; 95% CI: 0.60-1.38; P = 0.66) or protease-inhibitor-based cART (RH: 1.13; 95% CI: 0.77-1.66; P = 0.52). CONCLUSIONS Results from this non-randomized study suggest that NVPc might be safer to initiate in antiretroviral-experienced than in antiretroviral-naive patients with high CD4+ T-cell counts.
Evaluation of Aids and Equipment for the Bath and Toilet

It is often suspected by those presenting and supplying aids that while many are a great help to patients, others are rarely used. There is little information on the acceptability of various designs of bath and lavatory aids. Although new aids are designed and produced every year, few "Which" type surveys based on visits to the home have evaluated their good and bad features or even their safety. Acceptance of the tenet that aids should arrive with or before the patient is discharged from hospital to home is widespread but it is not known how well this is achieved in various parts of the country and under various supply arrangements.
Arterial compliance may influence baroreflex function in athletes and hypertensives.

The present study investigated arterial compliance as a possible influence on mean arterial pressure-heart rate (MAP-HR) reflex function in athletes and hypertensives. Aortic stiffness and systemic arterial compliance (SAC) were estimated in 25 elite male athletes and 25 age-matched sedentary controls. Blood pressure did not vary between groups, but SAC was higher in the athletic compared with the sedentary group (0.46 +/- 0.04 vs. 0.37 +/- 0.02 arbitrary compliance units; P = 0.03). In five hypertensives and six age-matched normals and in a subgroup of seven athletes and seven age-matched controls the sigmoidal MAP-HR reflex was assessed using phenylephrine and nitroprusside. In athletes compared with sedentary subjects MAP-HR reflex sensitivity was the same; however, the maximum tachycardia in response to blood pressure reduction was lower in the athletic group (87.1.1 +/- 3.7 vs. 97.1 +/- 2.9 beats/min; P = 0.05). Athletes had a higher blood pressure corresponding to 95% of the HR range (64.2 +/- 3.2 vs. 54.0 +/- 2.1 mmHg; P = 0.02), but there was no difference in the blood pressure corresponding to 5% of the HR range. The blood pressure excursion necessary to traverse the baroreceptor transducer range (MAPd) was therefore less in athletes compared with normals. The beta-index of aortic stiffness correlated closely with MAPd (R = 0.70; P < 0.01). In hypertensives reflex sensitivity was reduced, the minimum HR was elevated, and the MAPd was 56% greater compared with normals. (ABSTRACT TRUNCATED AT 250 WORDS)
Between-year variation and spatial dynamics of Cryptosporidium spp. and Giardia spp. infections in naturally infected rodent populations

SUMMARY Prevalence and abundance of Cryptosporidium spp. and Giardia spp. infections were studied over the 8-year period in 3 species of rodents in N.E. Poland (bank vole Myodes glareolus-1523; yellow-necked mouse Apodemus flavicollis- 638; common vole Microtus arvalis- 419). Prevalence was 53·8, 28·1 and 62·3% respectively for Cryptosporidium spp. and 58·3, 24·4 and 74·2% respectively for Giardia spp. Prevalence and abundance of infection varied markedly across 8 years of the study with 1998 and 2002 being years of higher prevalence and abundance, following changes in the densities of host species. The distribution of intestinal protozoa in forest rodents did not vary in the 3 isolated sites during the 4-year study. In the case of Cryptosporidium, fewer older animals carried infection and infections of the oldest bank and common voles were relatively milder. In the case of Giardia in yellow-necked mice, infections were more common in older age classes (2 and 3). The two species showed significant co-occurrence and in animals carrying both species there was a strong significant positive correlation between abundance of infection with each. These data are discussed in relation to the parasite genotypes identified in this region and in respect of the role of various ecological factors in shaping of intestinal protozoa communities.
Cycloprodigiosin hydrochloride, a new H+/Cl− symporter, induces apoptosis in human and rat hepatocellular cancer cell lines in vitro and inhibits the growth of hepatocellular carcinoma xenografts in nude mice

The effects of cycloprodigiosin hydrochloride (cPrG‐HCl), a new H+/Cl− symporter, were examined in liver cancer cell lines in vitro and in vivo. In the in vitro MTT assay, cPrG‐HCl inhibited the growth of 6 liver cancer cell lines (Huh‐7, HCC‐M, HCC‐T, dRLh‐84, and H‐35, hepatocellular carcinoma; HepG2, hepatoblastoma) in a dose‐ and time‐dependent manner. The 50% inhibitory concentrations (IC50) at 72 hours' treatment for liver cancer cell lines were 276 to 592 nmol/L, while that for isolated normal rat hepatocyte was 8.4 μmol/L. The cPrG‐HCl treatment of Huh‐7 cells induced apoptosis as confirmed by the appearance of a subG1 population, intranucleosomal DNA fragmentation, and chromatin condensation. cPrG‐HCl raised the pH of acidic organelles and lowered pHi (below pH 6.8). In addition, the apoptosis in Huh‐7 cells induced by cPrG‐HCl was strongly suppressed when the cells were cultured with imidazole, a cell‐permeable base. In thein vivoassay, nude mice bearing subcutaneous xenografted Huh‐7 cells received 2 weeks of treatment with cPrG‐HCl (1 or 10 mg/kg/d) subcutaneously. This treatment significantly inhibited tumor growth compared with the control after 8 days. The control mice were treated with 1% dimethylsulfoxide (DMSO) in saline (vehicle). A histopathological examination using the terminal deoxynucleotidyl transferase mediated dUTP biotin nick end labeling (TUNEL) method showed apoptosis in the treated tumor cells. No pathological changes were observed in any organs, and the serum alanine transaminase levels remained within normal limits. These results suggest that cPrG‐HCl may be useful for the treatment of hepatocellular carcinoma.
A pilot study on isolation of Asaia and detecting its co-presence with Plasmodium falciparum in two major malaria vectors in Senegal

The declining of malaria creates the opportunity to accelerate its elimination. However, the elimination program is threatened by the spread of insecticide resistance among Anopheles (An.) mosquitoes, stressing the urgent need for new vector control strategies. Recent evidence of stable infection of anopheles’ symbionts that could affect the development of Plasmodium parasites within mosquitoes, has paved the way for the use of such organisms to target and control malaria vector populations. We have isolated a new Asaia strain from a wild population of Anopheles gambiae s.l. and, for the first time, from natural population of Anopheles funestus, and insectary colony of Anopheles coluzzii. The new anopheline strain has been named Asaia (A.) aff. bogorensis GD01 because of its close relationship with A. aff. bogorensis isolated from plant flowers. We highlighted an antagonistic effect of A. aff. bogorensis GD01 on the sporogonic development of Plasmodium falciparum within the two major malaria vectors (An. gambiae and An. funestus) in Senegal. The putative impact of A. aff. bogorensis GD01 infection on the P. falciparum sporogonic development offers an opportunity for new malaria vector control approaches that can be added to the limited arsenal required to fulfil the World Health Organization (WHO) recommendations for searching new tools to achieve malaria elimination goal. Although this is an innovative and promising malaria control tool, more investigations are required to better characterize Asaia vs. Plasmodium interactions, before any Asaia¬-based intervention. This is required to ensure their safe use as an alternative or complementary vector control strategy to achieve malaria elimination goal. Key words: Asaia, Plasmodium falciparum, malaria, Anopheles gambiae, Anopheles funestus, Senegal.
Predictive-corrective incompressible SPH

We present a novel, incompressible fluid simulation method based on the Lagrangian Smoothed Particle Hydrodynamics (SPH) model. In our method, incompressibility is enforced by using a prediction-correction scheme to determine the particle pressures. For this, the information about density fluctuations is actively propagated through the fluid and pressure values are updated until the targeted density is satisfied. With this approach, we avoid the computational expenses of solving a pressure Poisson equation, while still being able to use large time steps in the simulation. The achieved results show that our predictive-corrective incompressible SPH (PCISPH) method clearly outperforms the commonly used weakly compressible SPH (WCSPH) model by more than an order of magnitude while the computations are in good agreement with the WCSPH results.
Temperature Influence on GaN HEMT Equivalent Circuit

The purpose of this letter is to present an experimental analysis of the temperature effects on the small-signal equivalent circuit of a GaN HEMT. With the aim of contributing to the exploration and advancement of this technology for high-power and high-temperature applications, the major intrinsic RF figures of merit together with the positive derivative of the real parts of the impedance parameters versus frequency are deeply investigated versus ambient temperature.
Neodymium-Doped Yttrium Aluminium Garnet Laser Treatment of Pediatric Venous Malformation in the Oral Cavity

BACKGROUND Treatment of venous malformations in the orofacial region remains a challenge. Laser therapy is an alternative treatment in inoperable cases. OBJECTIVE To retrospectively evaluate the effectiveness and complications associated with neodymium-doped yttrium aluminium garnet (Nd:YAG) laser treatment of oral venous malformations. MATERIALS AND METHODS A total of 10 children (mean age: 7.3 years; range: 10 months-15 years) with oral venous malformation were treated with Nd:YAG laser during 2005 to 2013. Clinical improvement, including degree of color lightening and size reduction, and treatment complications, including dyspigmentation, textural change, and scarring were evaluated. RESULTS Color clearing of 51% to 75% and >75% was seen in 25% and 45% of patients, respectively. Size reduction of 25% to 50%, 51% to 75%, and >75% was observed in 30%, 15%, and 45% of patients, respectively. Mild and moderate scarring was observed in 15% and 5% of cases, respectively. CONCLUSION Nd:YAG laser is a promising alternative treatment in pediatric patients with inoperable venous malformations in the oral cavity. Mild to moderate scarring was the most common complication.
Selection and constraints on offspring size‐number trade‐offs in sand lizards (Lacerta agilis)

The trade‐off between offspring size and number is a central component of life‐history theory, postulating that larger investment into offspring size inevitably decreases offspring number. This trade‐off is generally discussed in terms of genetic, physiological or morphological constraints; however, as among‐individual differences can mask individual trade‐offs, the underlying mechanisms may be difficult to reveal. In this study, we use multivariate analyses to investigate whether there is a trade‐off between offspring size and number in a population of sand lizards by separating among‐ and within‐individual patterns using a 15‐year data set collected in the wild. We also explore the ecological and evolutionary causes and consequences of this trade‐off by investigating how a female's resource (condition)‐ vs. age‐related size (snout‐vent length) influences her investment into offspring size vs. number (OSN), whether these traits are heritable and under selection and whether the OSN trade‐off has a genetic component. We found a negative correlation between offspring size and number within individual females and physical constraints (size of body cavity) appear to limit the number of eggs that a female can produce. This suggests that the OSN trade‐off occurs due to resource constraints as a female continues to grow throughout life and, thus, produces larger clutches. In contrast to the assumptions of classic OSN theory, we did not detect selection on offspring size; however, there was directional selection for larger clutch sizes. The repeatabilities of both offspring size and number were low and we did not detect any additive genetic variance in either trait. This could be due to strong selection (past or current) on these life‐history traits, or to insufficient statistical power to detect significant additive genetic effects. Overall, the findings of this study are an important illustration of how analyses of within‐individual patterns can reveal trade‐offs and their underlying causes, with potential evolutionary and ecological consequences that are otherwise hidden by among‐individual variation.
Pop hole passages and welfare in furnished cages for laying hens

1. This study included two designs of furnished cages for 16 hens; H-cages divided into two apartments by a partition with pop holes in the middle of the cage, and fully open O-cages, without a partition. The hypothesis was that in this rather large group of birds the pop hole partition would benefit the birds by allowing them to avoid or escape from potential cannibals, feather-peckers or aggressive hens. All cages had two nests, two perches and one litter box. 2. A total of 10 cages (5 H and 5 O) were stocked with Lohmann Selected Leghorn (LSL) and 8 cages (4 H and 4 O) with Hy-Line W36. No birds were beak-trimmed. 3. Heterophil/lymphocyte (H/L) ratios, duration of tonic immobility (TI) and exterior appearance (scoring of plumage condition and wounds at comb or around cloaca) were used as indicators of well-being. Total mortality and deaths due to cannibalism were also recorded. 4. Visits to nests and passages through partition pop holes were studied in samples of 35 and 21 birds, respectively, using a technique based on passive integrated transponder (PIT) tags. 5. Cage design (H- vs O-cage) had no effect on the welfare traits chosen. 6. Hy-Line birds showed higher H/L ratios, longer duration of TI and better plumage condition than LSL birds. These differences are discussed in terms of stress thresholds and copying strategies. 7. On days when a hen made visits to nests, the visiting frequency was 1·4 and the total time in the nest was 41 min on average. Hens made use of the pop hole passages between 1 and 8 times per hen and day. 8. Overall low levels of aggression, lack of injuries or deaths due to cannibalism, and plumage condition indicating moderate feather pecking, together imply a low need to escape. The pop holes were used frequently and birds distributed well between compartments showing that the system worked well. However, at this group size there was no evidence in the measured traits that H-cages provided a better housing environment.
Deadly Flies, Poor Profits, and Veterinary Pharmaceuticals: Sustaining the Control of Sleeping Sickness in Uganda

ABSTRACT Efforts to control neglected tropical diseases have increasingly focused on questions of implementation. But how should we conceptualize the implementation process? Drawing on ethnographic fieldwork between 2010 and 2012, in this article I explore efforts by a small-scale public–private partnership to use private veterinarians to sustainably control zoonotic sleeping sickness in Uganda. With a fundamental tension between business incentives and vector control, I show how divergences in knowledge, power, values, and social norms shaped project implementation and community responses. Reflecting more widely on the relationships between project plans and local realities, I argue that these encounters reveal the heuristic value in approaching global health interventions as evolving ‘social experiments. ’ This metaphor reveals the uncertainty inherent to dominant narratives and models, the role of available expertise in defining the limits of action, and the need for continuous adaption to synchronize with emergent social and institutional topographies.
Terpinen-4-ol induces autophagic and apoptotic cell death in human leukemic HL-60 cells.

BACKGROUND Terpinen-4-ol, a monoterpene, is found as the main component of essential oil extracts from many plants. In this study apoptotic and autophagic types of cell death induced by terpinen-4-ol and associated mechanisms were investigated in human leukemic HL-60 cells. MATERIALS AND METHODS The cytotoxicity of human leukemic U937 and HL-60 cells was determined by MTT assay. Cytochrome c release, expression of Bax, Bcl-2, Bcl-xl and cleaved Bid were determined by Western blotting. Cell morphology was examined under a transmission electron microscope. LC3-I/II, ATG5 and Beclin-1 levels were detected by immunoblotting. RESULTS Terpinen-4-ol exhibited cytotoxicity to human leukemic HL-60 but not U937 cells. The apoptotic response to terpinen-4-ol in HL-60 cells was due to induction of cytochrome c release from mitochondria and cleavage of Bid protein after the stimulation of caspase-8. There was a slightly decrease of Bcl-xl protein level. The characteristic cell morphology of autophagic cell death was demonstrated with multiple autophagosomes in the cytoplasm. At the molecular level, the results from Western blot analysis showed that terpinen-4-ol significantly induced accumulation of LC3-I/II, ATG5 and Beclin-1, regulatory proteins required for autophagy in mammalian cells. CONCLUSIONS Terpinen-4-ol induced-human leukemic HL-60 cell death was via both autophagy and apoptosis.
Parents as a Vector for Nosocomial Infection in the Neonatal Intensive Care Unit

To the Editor: The frequency of multiple births is increasing. Multiple gestations are more likely to result in premature birth and problems associated with prematurity. This may result in newborn siblings being admitted to the neonatal intensive care unit (NICU) simultaneously. We report two situations where the parent appeared to transfer or be the source of an organism that infected multiple siblings. Case 1. Siblings Al, A2, and A3 were born by cesarean section at 25 weeks gestation, after the mother developed premature rupture of members for baby Al. Placenta Al showed evidence of chorioamnionitis, but cultures were negative. Each infant weighed less than 1,000 g. Different nurses cared for each infant in three different rooms of our five-room NICU. Resident and attending physicians were the same for all three infants; however, the physicians could not recall moving directly from one sibling to another. Baby A2 developed sepsis and died on day 14 of life. Pseudomonas aeruginosa, an unusual isolate in our NICU, was grown from premortem blood, postmortem blood, and sputum specimens. The mother held the infant after its death. Infant Al developed necrotizing enterocolitis on day 19 of life and had positive endotracheal cultures for P aeruginosa on the same day. Subsequently, stool cultures were intermittently positive for P aeruginosa. In association with necrotizing enterocolitis, the infant developed enterocutaneous fistulae that intermittently drained stool. Infant A3 had multiple problems due to prematurity but had stabilized before suddenly deteriorating on day 46. This infant died 24 hours later and had postmortem cultures of lung, liver, and spleen positive for P aeruginosa. Genomic DNA was analyzed per protocol on a GenePath contourclamped homogeneous-field apparatus (Bio-Rad, Hercules, CA). Fingerprinting analysis was performed using the GelDoclOOO and Molecular Analyst restriction fragment-length polymorphism software (BioRad, Hercules, CA). The pulsed-field gel electrophoresis fingerprint for all three Pseudomonas isolates was identical. Case 2. Siblings Bl, B2, and B3 were born by cesarean section at 29 weeks. On day 29 of life, baby Bl developed Staphylococcus aureus bacteremia and expired. On day 52 of life, baby B2 developed S aureus conjunctivitis that was treated topically. S aureus is an uncommon isolate in our NICU. The father of these infants had a chronic open wound with prior cultures positive for S aureus. He visited the children several times a week. Pulsed-field gel electrophoresis typing of the isolates from babies Bl and B2 and the father's wound were identical.