High-throughput organ-on-chip platform with integrated programmable fluid flow and real-time sensing for complex tissue models in drug development workflows.

Drug development suffers from a lack of predictive and human-relevant in vitro models. Organ-on-chip (OOC) technology provides advanced culture capabilities to generate physiologically appropriate, human-based tissue in vitro, therefore providing a route to a predictive in vitro model. However, OOC technologies are often created at the expense of throughput, industry-standard form factors, and compatibility with state-of-the-art data collection tools. Here we present an OOC platform with advanced culture capabilities supporting a variety of human tissue models including liver, vascular, gastrointestinal, and kidney. The platform has 96 devices per industry standard plate and compatibility with contemporary high-throughput data collection tools. Specifically, we demonstrate programmable flow control over two physiologically relevant flow regimes: perfusion flow that enhances hepatic tissue function and high-shear stress flow that aligns endothelial monolayers. In addition, we integrate electrical sensors, demonstrating quantification of barrier function of primary gut colon tissue in real-time. We utilize optical access to the tissues to directly quantify renal active transport and oxygen consumption via integrated oxygen sensors. Finally, we leverage the compatibility and throughput of the platform to screen all 96 devices using high content screening (HCS) and evaluate gene expression using RNA sequencing (RNA-seq). By combining these capabilities in one platform, physiologically-relevant tissues can be generated and measured, accelerating optimization of an in vitro model, and ultimately increasing predictive accuracy of in vitro drug screening.

Subsampled digital holographic image reconstruction by a compressive sensing approach.

We show an in-line digital holographic image reconstruction from subsampled holograms with resolution improvement and lensless magnification with high noise immunity by a compressive sensing approach. Our method treats the sensed field as subsampled, low-pass filtered and projected on a Fresnel-Bluestein base in an inverse problem approach to image reconstruction with controlled lensless magnification. So, we have demonstrated by simulation and experimental results that the approach can reconstruct images with quality even when used in holograms obtained from unusual subsampling schemes.

Photorefractive moiré-like patterns for the multifringe projection method in Fourier transform profilometry.

In the present paper, the method of simultaneous moiré-like fringe pattern projection for Fourier transform profilometry is described. The photorefractive holographic interferometric process produces controlled moiré-like patterns with two or more different variation directions. Each low spatial frequency fringe pattern is experimentally obtained as a result of the superposition of two high spatial frequency sinusoidal gratings, with slightly different pitches, for each fringe variation direction. These dynamic moiré-like patterns are induced due to an optical holographic beating of the sinusoidal induced gratings in the volume of the photorefractive Bi12TiO20 (BTO) crystal sample used as dynamic holographic medium. Two or more moiré-like fringe patterns, with at least two different variation directions, simultaneously (or not), are projected onto the object surface. Thus, this is the 2D fringe projection stage of our proposed Fourier transform procedure to determine the profile of a simple object.

Branch-cut algorithm for optical phase unwrapping.

In this Letter, a proposal addressing the problem of two-dimensional phase unwrapping based on the theory of residues is presented. Here, wrapped phase maps with shifted phase jumps are used to balance residue charges. With this approach, we seek to minimize processing time and residue connection, which is essential in the development of branch-cut algorithms. Finally, a phase-unwrapping algorithm is applied to these wrapped maps, generated by Fourier transform profilometry to obtain three-dimensional profiles of objects illuminated by photorefractive moiré-like patterns generated in an experiment of real-time dynamic holography, and by fringe patterns generated with a Michelson interferometer.

Inheritance of kernel row number, a multicategorical threshold trait of maize ears.

Information about the inheritance of threshold traits is scarce, especially in plants. We examined the genetic control of kernel row number in maize (Zea mays). Knowledge of this inheritance is especially important because it is a primary component of grain yield. This trait has a discontinuous distribution. Characters like these are conceptualized as threshold traits. Crosses were made between the inbred line Geneze 3 (G3) with many kernel rows and the inbreds Argentino IV (A4) and Dente de Cravo (DC), with fewer kernel rows. The F(1) and F(2) generations and the backcrosses BC(11) and BC(21) were obtained for the combinations G3 x A4 and G3 x DC. These populations were evaluated under field conditions, and the kernel row number was determined by direct counting of approximately 14, 140 and 75 ears for the F(1), F(2) and backcrosses, respectively. Genetic control was determined through estimates of generation means and variance analysis and was also performed by Wright's method for threshold traits. It was found that genetic control is predominantly due to additive alleles. The component a, was greater than zero, additive variance was positive and the variance of dominance did not differ from zero. In the F(2) generation, the range of the kernel row number was 10 to 28 in G3 x A4, while in G3 x DC it was 12 to 26. Inheritance of the number of kernel rows, estimated by the two methods, gave similar results. This correspondence is due to adjusting of the data to the normal distribution.

Natural occurrence of mycotoxins and mycoflora of argentinien popcorn.

Argentina is the first popcorn exporting country worldwide. In 1997-1998 harvest season, 40,000 ha were sown with a production of 125,000 tons; 120,000 tons of this production were exported to more than 40 countries. The objectives of this study were to isolate and to identify the fungi present in this cereal and to assess the occurrence of mycotoxins in freshly harvested popcorn in Buenos Aires province, Argentina, in 1999. All popcorn samples showed fungal contamination. A total of 4,211 isolates were recovered from popcorn kernel samples. The prevalent species isolated wasFusarium verticillioides followed byPenicillium funiculosum, F. graminearum andAlternaria alternata. No aflatoxins, zearalenone, deoxynivalenol or ochratoxin A were detected in the 42 popcorn simples. All samples but one were contaminated with fumonisins (FB) in a range in ug/kg of (not detected-529) for FB1; (not detected-216) for FB2 and (not detected-103) for FB3. Fumonisin contamination levels in Argentinean popcorn were lower than observed in flint corn. No significant differences in fungal and fumonisins contamination levels were observed in the different tested hybrids.

Prognostic factors of mortality in newborns with necrotizing enterocolitis submitted to exploratory laparotomy.

PURPOSE: The aim of this study was to identify and assess mortality predictive factors in newborns with necrotizing enterocolitis (NEC) requiring emergency exploratory laparotomy. METHODS: A prospective study of 91 newborns with NEC submitted to exploratory laparotomy was conducted. Clinical outcomes were death and survival 60 days after surgery. Nine variables were analyzed: weight at birth, gestational age, intrauterine growth, sex, gas in the portal vein at abdominal x-ray, pneumoperitoneum, extent of the disease, operative strategies, and extension of bowel resection. Univariate and multivariate analyses were performed to identify mortality predictors. RESULTS: Mean weight at birth was 1,676 +/- 634.8 g, and mean gestational age was 34 +/- 2.8 weeks. Thirty-nine newborns (42.9%) presented intrauterine growth retardation. Operative techniques included bowel resection with enterostomy (80 patients), bowel resection with primary anastomosis (10 patients), and decompressive enterostomy (1 patient). Six deaths occurred caused by co-existing disease. NEC-related mortality rate was 46.15% (42 of 91). CONCLUSIONS: Two variables, intrauterine growth retardation, and diffuse bowel involvement, were predictive of mortality according to both univariate and multivariate analyses. Site of bowel involvement seems to be important mortality predictors in infants with NEC requiring surgery. The size of our population did not allow statistical analysis of this relationship. Further studies should focus on examining this aspect.

Hepatozoon canis infection associated with dog ticks of rural areas of Rio de Janeiro State, Brazil.

Hepatozoon canis is a tick-borne protozoan that infects dogs and has been reported throughout the world. Manifestation of H. canis infection varies from being sub-clinical in apparently healthy dogs to severe illness. The main vector of the infection is the dog tick, Rhipicephalus sanguineus although other species may also transmit this agent. H. canis has been reported previously in Brazil, but mostly as an occasional finding during laboratory exams and always associated with other diseases. The prevalence of H. canis in dogs of rural areas of Brazil has been little studied. For this study, 250 dogs from seven counties of Rio de Janeiro state were examined. All the dogs were from rural areas, near forest. Of the dogs examined, 26 dogs were from Seropédica, 82 from Itaguaí, 41 from Paracambi, 26 from Mangaratiba, 32 from Barra do Piraí, 32 from Piraí and 11 from Miguel Pereira. Blood smears from the peripheral blood of the ear were taken and ticks found on the dogs were collected for identification in the laboratory. Using blood smear evaluation, H. canis was identified in 39.2% of the animals examined. Other hemoparasites identified were Babesia canis (5.2%) and Ehrlichia canis (4.8%). Four tick species were found parasitizing the dogs: Amblyomma cajennense (23.6%), R. sanguineus (12.4%), Amblyomma aureolatum (2.8%) and Amblyomma ovale (2.0%). There was a positive correlation between the presence of A. cajennense and H. canis infection.

Sleep habits in Native Brazilian Bororo children.

Sleep behavior patterns in childhood are influenced by familial, cultural and environmental factors. In understanding sleep in Native Brazilian Bororo children, one should consider the influence of their culture on the child's sleep. This research analyzes sleep habits of Native Bororo children from the Meruri village, located in an Indian Reservation in the state of Mato Grosso. Fourty four children (24 M; 20 F) were evaluated; ages ranged from one month to 10 years, with a mean age of 4.9 years. Sleep characteristics were assessed by means of a standard questionnaire applied to the mothers. Cosleeping--sleeping together with family members--was a remarkable finding, in every child 0-2 year old and in 81.5% in the 2-10 years group. The second characteristic was sleeping with many people in the same room. There was an average of 5.1 people per room in the younger group and 3.9 people in the older group.

Sleep characteristics in children in the isolated rural African-Brazilian descendant community of Furnas do Dionísio, State of Mato Grosso do Sul, Brazil.

Developmental and cultural factors affect sleep habits in childhood. The objective of this research was to determine sleep habits of children in the isolated rural African-Brazilian community of Furnas do Dionísio. Mato Grosso do Sul, Brazil. The members of this community are closely related descendants of the ex-slave Dionísio, and remained in relative geographical isolation for about a century. Sleep characteristics of 55 children (35 M; 20 F), 2 to 10 year olds, were evaluated in interviews with their mothers. The results showed that cosleeping, in the same bed with family members, was present in 80.0% of the 2-3 year olds; decreasing to 25.0% of the 8-10 year olds. Only 5.4% of the children slept alone in their own bedroom. Mean number of persons per bedroom was 2.8. Only 7.0% of the bedrooms had TV; 98.1% slept in silence. The data obtained support the need to weigh cultural factors influence on sleep.

Sleep habits in native Brazilian Terena children in the state of Mato Grosso do Sul, Brazil.

Sleep habits in childhood vary in function of physiological factors. Cultural traits also influence sleep habits. This research evaluates sleep habits of Native Brazilian Terena children. The Terena group here studied live in the central region of Mato Grosso do Sul, Brazil, on the plains; they are peaceful and dedicated mainly to agriculture. Two villages were studied, Tereré and Córrego do Meio, both in Reservations. Sleep characteristics of 67 children (40M;27F), 2 to 10 year olds, were evaluated in interviews with their mothers. The results evidenced that cosleeping, in the same bed with family members is the standard Terena pattern present in every evaluated child. The presence of two or more beds and a mean of five or more people in each bedroom was the typical finding. The authors propose that cosleeping and the presence of numerous family members reflect the high values attributed to family links in the Terena culture.

[Fetal hydronephrosis: postnatal management and follow up]. / Hidronefrose fetal: abordagem pós-natal e seguimento.

OBJECTIVE: Fetal hydronephrosis is being detected with increasing frequency and probably this observation will increase as the quality of ultrasound equipment improves. This study evaluated etiology and postnatal clinical outcomes of prenatally detected hydronephrosis. METHODS: In a period of 13 years 148 infants were referred with fetal hydronephrosis. The initial evaluation, after prophylaxis, included ultrasound and voiding cystography. Sequential evaluation was determined by initial findings. RESULTS: Postnatal predominant diagnosis were pelviureteric junction obstruction (24%) and hydronephrosis without obstruction (18%). Follow up median was 38.7 months. Renal function deteriorated in 13 (8.8%) children and 11 (7.4%) died during follow up. Bad prognosis was associated with urethral obstruction. CONCLUSIONS: Fetal hydronephrosis is a clue of urinary tract anomalies. Urinary tract infections and delay in postnatal diagnosis must be prevented in children with this uropathy.

[Kabuki make-up syndrome]. / A síndrome da máscara do Cabúqui.

The authors present an original case, the first in Brazil and Latin America, of the Kabuki make-up syndrome. To diagnose KMS, the authors point out the importance of the "Pentad of Niikawa", a term created by them to indicate the five basic features of the syndrome. Also new symptoms and signs which might be part of the phenotype of KMS are described. The authors emphasize that studies concerning KMS be widely spread, in order to identify new cases.

Multicenter clinical trial on the efficacy and acceptability of a single contraceptive implant of nomegestrol acetate, Uniplant.

Uniplant, a single Silastic implant containing nomegestrol acetate, provides contraceptive efficacy for one year. Uniplant use for one year was studied in 1,803 healthy women of reproductive age, enrolled from 10 centers in 9 countries, after informed consent. Implants were placed subdermally either in the upper arm or in the gluteal region. Two-hundred-seventy-six subjects discontinued prior to completing one year of study. Cumulative discontinuation rate at 12 months was 15.72%. Medical reasons for discontinuation were principally menstrual-related. Fifteen pregnancies occurred during the one year study period, resulting in a 12-month net cumulative pregnancy rate of 0.94%. Approximately 56% of subjects using Uniplant had bleeding patterns similar to normal menstruation. Results from this study confirm that Uniplant is an efficient, well tolerated, 12-month contraceptive implant, with the advantage of easier insertion and removal of the single implant compared to other multiple implant methods.

Comparative study on the efficacy and acceptability of two contraceptive pills administered by the vaginal route: an international multicenter clinical trial.

The efficacy and acceptability of two widely used oral contraceptive tablets, one containing 250 mg levonorgestrel and 50 micrograms ethinyl estradiol and the other containing 150 micrograms desogestrel and 30 micrograms ethinyl estradiol, administered by the vaginal route were compared in 1055 women studied over 12,630 woman-months of vaginal contraceptive pill use. This multicenter clinical trial was performed in nine countries of the developing world by the "South to South Cooperation in Reproductive Health," an organization founded by scientists from the Third World working in the area of reproductive health, and the study was developed and coordinated by one of these centers. The findings of this study confirm the efficacy of both these tablets when administered by the vaginal route. Involuntary pregnancy rates at 1 year of 2.78 for subjects in the levonorgestrel group and 4.54 for subjects the desogestrel group showed no statistically significant difference between the two groups. However, total discontinuation rates of 47.01 for subjects in the levonorgestrel group and 56.33 for subjects in the desogestrel group showed a statistically significant difference between the two groups, and discontinuation rates attributable to prolonged bleeding of 0.6 for subjects in the levonorgestrel group and 3.2 for subjects in the desogestrel group were also significantly higher in the group of subjects using the desogestrel vaginal contraceptive pill. Blood pressure remained at admission values throughout treatment. A statistically significant weight increase from admission values occurred in both groups of subjects.

PIP: Efficacy and acceptability of 2 combined oral contraceptive pills administered vaginally are summarized. This is the 1st collaborative trial published by the South to South Cooperation in Reproductive Health. 1055 women participated in 12,630 cycles, in 9 countries, from June 1988 to May 1991. The pills were commercially available tablets containing 50 mcg ethinyl estradiol and 250 mg levonorgestrel (Schering AG, Sao Paulo, Brazil), or 30 mcg ethinyl estradiol and 15 mcg desogestrel (Organon, Sao Paulo, Brazil). Subjects were aged 17-39 younger and of lower parity from Mexico and Dominican Republic and older from Egypt and China. All had at least 1 pregnancy. 675 participated for 6 months, 470 for 1 year, 364 for 18 months, and 210 for 2 years. The 1-year discontinuation rate averaged 47.01% for the levonorgestrel group and 56.33% for the desogestrel group (p = 0.0061); 2-year discontinuation rates were 48.01% and 69.36, respectively, explained in part by higher involuntary pregnancy rates and prolonged bleeding rates in the desogestrel group. The most common medical reasons for stopping contraception were unplanned pregnancy, vaginal or vulval irritation, nausea, vaginal discharge and headache. Vaginal irritation was reported by 1%, 9 in each group. There were 32 pregnancies, 14 in the levonorgestrel and 18 in the desogestrel group. 17 were in missed pill cycles and the rest were method failures, 6 in the levonorgestrel group and 9 in the desogestrel group. The Pearl index varied from 0 in Nigeria to 12.24 in Mexico, and was 2.45 for levonorgestrel vs. 3.74 for desogestrel. There was a wide variation in discontinuation rates by center: Brazil and China had few, while many women from Dominican Republic, Mexico and Zambia left the study. Bleeding problems were common complaints, more so in the desogestrel group. There were 363 women with intermenstrual bleeding (only once in 80%), 148 with spotting (only twice in 65%). Bleeding duration was significantly less in pill cycles than baseline, pressure. Women gained an average of 1 kg over 2 years, more in the desogestrel group. The pregnancy rate of 2.78 is within the range reported for levonorgestrel rings.

Long-lasting ovulation inhibition with a new injectable progestagen ORG-2154.

A new long-acting injectable progestagen was tested in 15 women who volunteered for the study. The occurrence of ovulation was assumed by the elevation of progesterone levels above 2ng/ml following a pre-ovulatory estradiol peak. Following a 200mg injection, ovulation was inhibited in all 15 women for five to ten months. In four subjects the interval between the injection and the first progesterone peak was five months. For eight, the interval was six to eight months. In the other three women, ovulation occurred more than eight months following injection. Bleeding episodes, similar to menstruation, occurred in most patients. Bleeding intervals lasting longer than 45 days occurred in nine subjects but more prolonged amenorrhea lasting longer than 60 days was reported by only five subjects. Blood chemistry which included blood cell counts, cholesterol, glucose, alkaline phosphatase, transaminases, urea nitrogen and creatinine remained within normal limits throughout the treatment.

Pharmacokinetics of ethynyloestradiol in women for different populations.

The pharmacokinetics of a dose of 50 microgram ethynyloestradiol administered orally was studied in fourteen centres. Absorption was rapid and the highest serum concentrations of total ethynyloestradiol were found in most subjects at 1 h and by 24 h concentrations were less than 250 pg/ml. Calculation of the half-lives for absorption, distribution and elimination showed wide variations between subjects, the half-life of elimination varying from 2.5 h to more than 30 h. Bioavailability as measured by the area under the serum ethynyloestradiol concentration-time curve also showed more than a ten-fold variation. Intra-centre differences in the various parameters measured were as large as the inter-centre differences.

Return of ovarian function and endometrial morphology in women treated with norethisterone oenanthate: a pilot study.

A comparative pilot study was undertaken in three centers to determine the time of return of ovulation after the injection of the steroidal contraceptive norethisterone oenanthate (NET-OEN). The effect of the compound on the endometrium and some properties of cervical mucus were also assessed. Increases in plasma progesterone levels suggested that ovulation resumed in all six women in Bahia within 60 days of injection of NET-OEN, whereas in Bangkok and New Delhi only two women in each center ovulated within this time. The difference in the time of return of ovulation between women in Bahia (mean time 42 days) and those in Bangkok and New Delhi (92.5 days) was statistically significant. Follicular function returned earlier than luteal function: all six women in Bahia and Bangkok and five of the six in New Delhi showed evidence of follicular activity within 60 days. All endometrial biopsies, obtained at a time of increased progesterone production, were secretory and suggested that administration of the gestagen did not exert a prolonged suppression of endometrial activity. In general, changes in cervical mucus were consistent with variations in plasma steroid levels.