Miracle-dz/UniFAR-FTUs huggingface dataset:
Ketoconazole Pharmacokinetics in Continuous Ambulatory Peritoneal Dialysis

Ketoconazole, a new oral drug, has minimal toxicity and a broad spectrum of antifungal activity. To determine its usefulness in fungal peritonitis associated with continuous ambulatory peritoneal dialysis (CAPD), we carried out nine pharmacokinetic studies in five patients on CAPD. Serum levels of ketoconazole in CAPD patients were lower than in normal controls, and some patients did not appear to absorb the drug. We did not detect ketoconazole in the peritoneal fluid of any patient, even in the presence of peritoneal inflammation. One should not use this agent in the treatment of fungal peritonitis at daily doses of 400 mg or less because such a dose achieves only poor peritoneal fluid concentrations. Continuous ambulatory peritoneal dialysis (CAPD) has become an attractive alternative to hemodialysis for many patients with chronic renal failure. However, a major drawback with this technique is peritonitis (1). Although most of these infections are due to staphylococci (I), fungal peritonitis appears to be increasing as experience with CAPD grows (2,3). The treatment of such peritonitis is hampered by the poor penetration of amphotericin B into the peritoneal fluid (2), chemical peritonitis when amphotericin B is instilled directly into the cavity (3), and the limited spectrum of activity of flucytosine -a drug which readily penetrates into the peritoneal fluid (4). Ketoconazole is less toxic than amphotericin B and easier to administer and it has a much broader antifungal spectrum than flucytosine. The value of ketoconazole in fungal peritonitis remains to be established, and we have only limited data concerning its penetration into the peritonal cavity (2, 5). In this study we assessed the serum and peritoneal-fluid levels of ketoconazole in patients on CAPD.
Influence of different physical modalities on the female sexual function

REFERENCES Female sexual dysfunction (FSD) may be associated with negative experiences in sexual relationships and physiological events in a woman's life, such as pregnancy, breastfeeding and menopause. However, little is known about the physical activity on female sexual function. Thus, the aim of this study was to investigate if the type of physical activity can influence female sexual function.
The association of fish consumption and its urinary metabolites with cardiovascular risk factors: the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP)

ABSTRACT Background Results from observational studies regarding associations between fish (including shellfish) intake and cardiovascular disease risk factors, including blood pressure (BP) and BMI, are inconsistent. Objective To investigate associations of fish consumption and associated urinary metabolites with BP and BMI in free-living populations. Methods We used cross-sectional data from the International Study of Macro-/Micronutrients and Blood Pressure (INTERMAP), including 4680 men and women (40–59 y) from Japan, China, the United Kingdom, and United States. Dietary intakes were assessed by four 24-h dietary recalls and BP from 8 measurements. Urinary metabolites (2 timed 24-h urinary samples) associated with fish intake acquired from NMR spectroscopy were identified. Linear models were used to estimate BP and BMI differences across categories of intake and per 2 SD higher intake of fish and its biomarkers. Results No significant associations were observed between fish intake and BP. There was a direct association with fish intake and BMI in the Japanese population sample (P trend = 0.03; fully adjusted model). In Japan, trimethylamine-N-oxide (TMAO) and taurine, respectively, demonstrated area under the receiver operating characteristic curve (AUC) values of 0.81 and 0.78 in discriminating high against low fish intake, whereas homarine (a metabolite found in shellfish muscle) demonstrated an AUC of 0.80 for high/nonshellfish intake. Direct associations were observed between urinary TMAO and BMI for all regions except Japan (P < 0.0001) and in Western populations between TMAO and BP (diastolic blood pressure: mean difference 1.28; 95% CI: 0.55, 2.02 mmHg; P = 0.0006, systolic blood pressure: mean difference 1.67; 95% CI: 0.60, 2.73 mmHg; P = 0.002). Conclusions Urinary TMAO showed a stronger association with fish intake in the Japanese compared with the Western population sample. Urinary TMAO was directly associated with BP in the Western but not the Japanese population sample. Associations between fish intake and its biomarkers and downstream associations with BP/BMI appear to be context specific. INTERMAP is registered at www.clinicaltrials. gov as NCT00005271.
Inclusion of Mentha piperita, Anethum graveolence and Ocimum basilicum in Yogurt and their effect on the Inhibition of Enzyme Relevant to Hypertension and type-2 Diabetes

Medicinal herbs are widely used both in culinary and as therapeutic herbs in traditional medicine. The present study investigated the effects of inclusion of herbs into milk on yogurt formation and the effects on a-amylase, a-glucosidase and angiotensin I converting enzyme (ACE) activities. Pasteurised cowâ€™s milk and starter culture mixture (Streptococcus thermophilus and Lactobacillus acidophilus) were incubated at 41ÂoC in the presence or absence of herbalwater extracts followed by storage at 4ÂoC. The addition of herbs into yogurt reduced pH at a faster rate than that in plain yogurt. pH 4.5 was achieved fastest for Anethum graveolenceâ€“yogurt (240 minutes) followed by Ocimum basilicum- and Mentha piperita-yogurts (both 300 minutes) and plain-yogurt (420 minutes). The TTA for these herbal-yogurts were higher than plain yogurt at all time points during the incubation. Both O. basilicum and M. piperita-yogurts had the same rate of TTA production whereas A. graveolence-yogurt had higher rate of TTA production (p<0.05) between the 180th- 240th minute of fermentation. All herbal yogurts had higher (p<0.05) antioxidant activity than plain yogurt. The OPA peptides in herbal yogurts increased by 28-36% by the 7th day of storage, with highest increase in M. piperita- followed by A. graveolence- and O. basilicum-yoghurts (33.4, 31.5, 30.2 mg/g respectively). All herbal yogurts showed higher anti-ACE activity than plain yogurt at respective storage periods. M. piperita-yogurt had the highest inhibitory effect on ACE activity throughout the storage period (84.9, 87.3, 74.0 and 63.6 % on day 0, 7, 14, 21 and 28 respectively). O. basilicumâ€“yogurts showed higher (p<0.05) anti- ACE activity than plain yogurt only on day 0 of storage. A. graveolence-yogurt however showed stronger anti-ACE activity than O. basilicum-yogurt compared to plain-yogurt on all storage days except on day 28. Most potent effect on a-amylase inhibition on day 7 of storage was shown by A. graveolence-yogurt followed by M. piperita and O. basilicum-yogurts (26.6, 37.3, and 42.0% respectively). All herbal-yogurts also inhibited a-glucosidase, with highest inhibition on day 7 caused by A. graveolence-yogurt, M. piperita-yogurt and O. basilicum-yogurt (38.7, 22.6 and 15.7% respectively). The herbs studied modified yogurt formation with beneficial effects on enzymes important in the management of hypertension and diabetes mellitus.
Biallelic Mutations in MTPAP Associated with a Lethal Encephalopathy

Abstract Background A homozygous founder mutation in MTPAP/TENT6, encoding mitochondrial poly(A) polymerase (MTPAP), was first reported in six individuals of Old Order Amish descent demonstrating an early-onset, progressive spastic ataxia with optic atrophy and learning difficulties. MTPAP contributes to the regulation of mitochondrial gene expression through the polyadenylation of mitochondrially encoded mRNAs. Mitochondrial mRNAs with severely truncated poly(A) tails were observed in affected individuals, and mitochondrial protein expression was altered. Objective To determine the genetic basis of a perinatal encephalopathy associated with stereotyped neuroimaging and infantile death in three patients from two unrelated families. Methods Whole-exome sequencing was performed in two unrelated patients and the unaffected parents of one of these individuals. Variants and familial segregation were confirmed by Sanger sequencing. Polyadenylation of mitochondrial transcripts and de novo synthesis of mitochondrial proteins were assessed in patient's fibroblasts. Results Compound heterozygous p.Ile428Thr and p.Arg523Trp substitutions in MTPAP were recorded in two affected siblings from one family, and a homozygous p.Ile385Phe missense variant identified in a further affected child from a second sibship. Mitochondrial poly(A) tail analysis demonstrated shorter posttranscriptional additions to the mitochondrial transcripts, as well as an altered expression of mitochondrial proteins in the fibroblasts of the two siblings compared with healthy controls. Conclusion Mutations in MTPAP likely cause an autosomal recessive perinatal encephalopathy with lethality in the first year of life.
Going to extremes: the Goldilocks/Lagom principle and data distribution

Numerical data in biology and medicine are commonly presented as mean or median with error or confidence limits, to the exclusion of individual values. Analysis of our own and others’ data indicates that this practice risks excluding ‘Goldilocks’ effects in which a biological variable falls within a range between ‘too much’ and ‘too little’ with a region between where its function is ‘just right’; a concept captured by the Swedish term ‘Lagom’. This was confirmed by a narrative search of the literature using the PubMed database, which revealed numerous relationships of biological and clinical phenomena of the Goldilocks/Lagom form including quantitative and qualitative examples from the health and social sciences. Some possible mechanisms underlying these phenomena are considered. We conclude that retrospective analysis of existing data will most likely reveal a vast number of such distributions to the benefit of medical understanding and clinical care and that a transparent approach of presenting each value within a dataset individually should be adopted to ensure a more complete evaluation of research studies in future.
Social Isolation and Memory Decline in Later-life

Abstract Objectives To investigate associations between level and changes in social isolation and in memory in older men and women. Methods The sample included 6,123 women and 5,110 men aged 50+ from the English Longitudinal Study of Aging (ELSA). Extended latent change score models from six measurement occasions every 2 years from 2002 were used to investigate associations between social isolation and memory. Models were adjusted for age, socioeconomic position, and health. Results Social isolation increased and memory decreased over time. Among men an initially high level of social isolation was associated with a somewhat greater decrease in memory. Among women a greater increase in social isolation predicted a greater decrease in memory and a larger change in social isolation was associated with further larger changes in isolation, although when social isolation reached a higher level it subsequently decreased. Conclusions Results suggest that the association between social isolation and memory decline arises because social isolation is associated with increased memory decline rather than poor memory leading to increases in social isolation. Men with high levels of social isolation and women with accumulated social isolation over time are especially affected as these patterns of isolation were associated with more profound memory decline.
Acute effects of resonance frequency breathing on cardiovascular regulation

Acute slow breathing may have beneficial effects on cardiovascular regulation by affecting hemodynamics and the autonomic nervous system. Whether breathing at the resonance frequency (RF), a breathing rate that maximizes heart rate oscillations, induces differential effects to that of slow breathing is unknown. We compared the acute effects of breathing at either RF and RF + 1 breaths per minute on muscle sympathetic nervous activity (MSNA) and baroreflex function. Ten healthy men underwent MSNA, blood pressure (BP), and heart rate (HR) recordings while breathing for 10 min at their spontaneous breathing (SB) rate followed by 10 min at both RF and RF + 1 randomly assigned and separated by a 10‐min recovery. Breathing at either RF or RF + 1 induced similar changes in HR and HR variability, with increased low frequency and decreased high frequency oscillations (p < .001 for both). Both respiration rates decreased MSNA (−5.6 and −7.3 bursts per min for RF and RF + 1 p < .05), with the sympathetic bursts occurring more often during mid‐inspiration to early expiration (+57% and + 80%) and longer periods of silence between bursts were seen (p < .05 for RF + 1). Systolic BP was decreased only during RF (−4.6 mmHg, p < .05) but the decrease did not differ to that seen during RF + 1 (−3.1 mmHg). The sympathetic baroreflex function remained unchanged at either breathing rates. The slope of the cardiac baroreflex function was unaltered but the cardiac baroreflex efficiency was improved during both RF and RF + 1. Acute breathing at either RF or RF + 1 has similar hemodynamic and sympatho‐inhibitory effects in healthy men.
Manejo conservador de los esguinces de tobillo

LOS ENGUINCES SON FRECUENTES EN EL DEPORTE, OCUPAN UNO DE LOS PRIMEROS LUGARES DE INCIDENCIA. EL DIAGNOSTICO OPORTUNO Y ADECUADO DEL GRADO, PREVIENE COMPLICACIONES. SE CLASIFICAN EN GRADOS: GRADO I, GRADO II Y GRADO III DE ACUERDO A LOS DATOS CLINICOS PRESENTES. ANTERIORMENTE EL TRATAMIENTO CONSISTIA EN INMOVILIZACION DE LA ARTICULACION. EN LA ACTUALIDAD SE PREFIERE LA MOVILIZACION TEMPRANA Y REHABILITACION PROGRESIVA. UN ESGUINCE MAL TRATADO TRAE COMO CONSECUENCIAS SINTOMAS RESIDUALES COMO DOLOR PERSISTENTE, EDEMA E INESTABILIDAD CRONICA. LA EVOLUCION DE LOS ENGUINCES GRADO I Y GRADO II ES EL PROMEDIO DE 10 DIAS Y 16 DIAS RESPECTIVAMENTE, CON UN TRATAMIENTO ADECUADO. SE HA REPORTADO QUE LA FRECUENCIA DE LESIONES PUEDE DISMINUIRSE CON UN PROGRAMA DE FORTALECIMIENTO Y PROPIOCEPCION, ASI COMO CON EL USO DE TOBILLERAS ESPECIALES. SE CONSIDERA QUE SI SE SELECCIONAN APROPIADAMENTE LAS MODALIDADES TERAPEUTICAS Y LA REHABILITACION, DISMINUYE EL TIEMPO DE RECUPERACION. SI LAS PERSONAS NO DEPORTISTAS SE LES DA UN TRATAMIENTO ACELERADO, DISMINUIRIA LA INCAPACIDAD Y LAS COMPLICACIONES, MEJORANDO LA CALIDAD DE VIDA.
Biofilm-Forming by Carbapenem Resistant Enterobacteriaceae May Contribute to the Blood Stream Infection

Bloodstream infection (BSI) due to carbapenem-resistant Enterobacteriaceae (CRE) has a high mortality rate and is a serious threat worldwide. Ten CRE strains (eight Enterobacter cloacae, one Klebsiella pneumoniae and one Citrobacter freundii) were isolated from the blood of nine patients, a percentage of whom had been treated with indwelling devices. The steps taken to establish cause included minimum inhibitory concentration (MIC) tests, a pulsed-field gel electrophoresis (PFGE), biofilm study, a multiplex PCR for resistant genes of carbapenemases and extended-spectrum beta-lactamases (ESBLs), and plasmid incompatibility typing. All strains showed a tendency toward resistance to multiple antibiotics, including carbapenems. Frequently isolated genes of ESBLs and carbapenemases include blaTEM-1 (four strains), blaSHV-12 (four strains) and blaIMP-1 (six strains). A molecular analysis by PFGE was used to divide the XbaI-digested genomic DNAs of 10 CRE strains into eight patterns, and the analysis showed that three E. cloacae strains detected from two patients were either identical or closely related. The biofilm production of all CRE strains was examined using a microtiter biofilm assay, and biofilm growth in continuous flow chambers was observed via the use of a confocal laser scanning microscope. Our study indicates that biofilm formation on indwelling devices may pose a risk of BSI due to CRE.
Survey of Trypanosoma (Kinetoplastida: Trypanosomatidae) Infection in Monte Negro Municipality, State of Rondônia, Western Amazon, with First Record of T. evansi in the state.

INTRODUCTION Trypanosomes can infect humans and animals. This is the first record of the occurrence of Trypanosoma evansi in Rondônia. METHODS Blood samples were collected from 7 dogs and 22 humans. Furthermore, triatomines and tabanids were collected. RESULTS It was observed that 42.8% of the dogs tested positive for T. evansi and 14.3% presented mixed infection; 15% of the triatomines tested positive for flagellates identified as T. cruzi TCI (3 specimens), T. cruzi TCI, and T. rangeli (1 specimen), and one with T. cruzi TCV. Two tabanids were infected with T. theileri. CONCLUSIONS These findings may benefit vector control strategies.
Tetrahydrobiopterin restores microvascular dysfunction in young adult binge drinkers.

BACKGROUND Repeated binge drinking is associated with reduced microvascular function. However, microvascular responses to pathophysiological stimulus such as high pressure as well as potential mechanisms that underlie binge-induced microvascular dysfunction are unknown. Therefore, using an ex vivo experimental model, we examined microvascular responses following a brief period of high intraluminal pressure in isolated arterioles from young adults who have a history of repeated binge drinking. In addition, we examined if the application of the endothelial nitric oxide synthase cofactor, tetrahydrobiopterin, would restore microvascular function in response to flow and high intraluminal pressure in young adult binge drinkers. METHODS Isolated subcutaneous adipose arterioles were obtained from young adult binge drinkers (BD; n = 14), moderate drinkers (MODs; n = 10), and alcohol abstainers (ABs; n = 12; mean age: 23.7 ± 0.5 yrs and body mass index: 23.4 ± 0.4 kg m-2 ). Arteriolar flow-induced dilation (FID, pressure gradient: ∆10-100 cm H2 O) was measured before and after acute high intraluminal pressure with and without tetrahydrobiopterin. RESULTS Before high pressure, FID at Δ60 and Δ100 cm H2 O pressure gradient in BDs was 14% lower and 18% lower respectively than ABs (P < 0.05), while MODs and ABs had similar FID across all pressure gradients (P ≥ 0.2). After high pressure, FID in BDs was further reduced by 10% (P < 0.0005) and this impairment was ameliorated by the treatment of tetrahydrobiopterin (4-26% higher, P < 0.005). In contrast, FID after high pressure did not change in MODs and ABs (P ≥ 0.5). CONCLUSIONS Microvascular dysfunction in young adult binge drinkers may be exacerbated with acute pathophysiological stimulus. These binge-induced dysfunctions may be reversed by tetrahydrobiopterin, which suggests a role of oxidative stress and/or uncoupled endothelial nitric oxide synthase in binge drinking.
Development-Disrupting Chitin Synthesis Inhibitor, Novaluron, Reprogramming the Chitin Degradation Mechanism of Red Palm Weevils

Disruption in chitin regulation by using chitin synthesis inhibitor (novaluron) was investigated to gain insights into the biological activity of chitinase in red palm weevils, an invasive pest of date palms in the Middle East. Impact of novaluron against ninth instar red palm weevil larvae was examined by dose-mortality response bioassays, nutritional indices, and expression patterns of chitinase genes characterized in this study. Laboratory bioassays revealed dose-dependent mortality response of ninth-instar red palm weevil larvae with LD50 of 14.77 ppm of novaluron. Dietary growth analysis performed using different doses of novaluron (30, 25, 20, 15, 10, and 5 ppm) exhibited very high reduction in their indexes such as Efficacy of Conversion of Digested Food (82.38%) and Efficacy of Conversion of Ingested Food (74.27%), compared with control treatment. Transcriptomic analysis of red palm weevil larvae characterized numerous genes involved in chitin degradation including chitinase, chitinase-3-like protein 2, chitinase domain-containing protein 1, Endochitinase-like, chitinase 3, and chitin binding peritrophin-a domain. However, quantitative expression patterns of these genes in response to novaluron-fed larvae revealed tissue-specific time-dependent expression patterns. We recorded overexpression of all genes from mid-gut tissues. Growth retarding, chitin remodeling and larvicidal potential suggest novaluron as a promising alternate for Rhynchophorus ferrugineus management.
MODELLING A COMBINED A2O AND RBC PROCESS UNDER DO VARIATION BY USING AN ACTIVATED SLUDGE-BIOFILM HYBRID MODEL

A hybrid model which incorporated a biofilm model into the General Dynamic Model (GDM) was developed to predict the effluent quality of a combined activated sludge and biofilm process TNCU1. The system was performed under three different dissolved oxygen (DO) conditions in the oxic tank, including 2.0, 1.0, and 0.5 mg/L. When DO increased from 0.5 to 2.0 mg/L, soluble biodegradable substrate (SS) and soluble phosphate (PO4) in the effluent were not influenced significantly. Their removal efficiencies were above 92 and 94 %. Ammonia-nitrogen (NH3) removal efficiency increased from 36 % to 83 % and nitrate-nitrogen (NO3) increased from 1.7 to 2.9 mg/L. In biofilm, when DO was 2.0 mg/L, active autotrophic biomass (ZA) fraction was 15.7% (surface) to 12.9% (substratum). But when DO was 0.5 mg/L, ZA fraction became lower and the fraction was 6.2% (surface) to 3.5 % (substratum). The fraction of active non-poly-P heterotrophic biomass (ZH) in the biofilm did not vary significantly, the values were about 28% to 35%. ZI decreased as DO increased. SS in the biofilm did not vary significantly and was maintained at about 2.0 mg/L. When DO increased, NO3 also increased, NH3 decreased from 13.1 to 1.8 mg/L in biofilm. SUBJECT HEADING LIST TO THE CEDB: Biological treatment, Wastewater treatment, Activated sludge process, Biofilm, Rotating biological contactor, Models
Phage Therapy as an Approach to Control Salmonella enterica serotype Enteritidis Infection in Mice.

INTRODUCTION Salmonella enterica serotype Enteritidis (S. Enteritidis) is a cause of food-borne human illness. Given the prevalence of antibiotic resistance of Salmonella Enteritidis and the lack of antibiotic efficacy in future years, its replacement with other agents is necessary. One of the most useful agents is bacteriophages. METHODS S. Enteritidis was identified using a multiplex polymerase chain reaction assay. The effective bacteriophages were isolated from hospital wastewater samples. The effects of the bacteriophages were evaluated both in vitro and in vivo. RESULTS The phage SE20 belonged to the Podoviridae family, and the genome size was 40 kb. The evaluation of phage SE20 at variable pH ranges showed its susceptibility to pH < 3 and pH > 12. The animal model showed that mice infected with S. Enteritidis developed hepatomegaly and splenomegaly, but did not experience gastrointestinal complications after receiving the bacteriophages. CONCLUSIONS The results of this study suggest that phage SE20 is a promising candidate for controlling salmonellosis caused by Salmonella Enteritidis.