Latent tuberculosis infection treatment completion in Biscay: differences between regimens and monitoring approaches.

Introduction: Contact tracing and treatment of latent tuberculosis infection (LTBI) is a key element of tuberculosis (TB) control in low TB incidence countries. A TB control and prevention program has been active in the Basque Country since 2003, including the development of the nurse case manager role and a unified electronic record. Three World Health Organization-approved LTBI regimens have been used: isoniazid for 6 months (6H), rifampicin for 4 months (4R), and isoniazid and rifampicin for 3 months (3HR). Centralized follow-up by a TB nurse case manager started in January 2016, with regular telephone follow-up, telemonitoring of blood test results, and monitoring of adherence by electronic review of drugs dispensed in pharmacies. Objective: To estimate LTBI treatment completion and toxicity of different preventive treatment regimens in a real-world setting. Secondary objective: to investigate the adherence to different approaches to preventive treatment monitoring. Methods: A multicentre retrospective cohort study was conducted using data collected prospectively on contacts of patients with TB in five hospitals in Biscay from 2003 to 2022. Results: A total of 3,066 contacts with LTBI were included. The overall completion rate was 66.8%; 86.5% of patients on 3HR (n = 699) completed treatment vs. 68.3% (n = 1,260) of those on 6H (p < 0.0001). The rate of toxicity was 3.8%, without significant differences between the regimens. A total of 394 contacts were monitored by a TB nurse case manager. In these patients, the completion rate was 85% vs. 67% in those under standard care (p < 0.001). A multivariate logistic regression model identified three independent factors associated with treatment completion: being female, the 3HR regimen, and nurse telemonitoring. Conclusion: 3HR was well tolerated and associated with a higher rate of treatment completion. Patients with nurse telemonitoring follow-up had better completion rates.

Frequency-domain hot-wire sensor and 3D model for thermal conductivity measurements of reactive and corrosive materials at high temperatures.

High temperature solids and liquids are becoming increasingly important in next-generation energy and manufacturing systems that seek higher efficiencies and lower emissions. Accurate measurements of thermal conductivity at high temperatures are required for the modeling and design of these systems, but commonly employed time-domain measurements can have errors from convection, corrosion, and ambient temperature fluctuations. Here, we describe the development of a frequency-domain hot-wire technique capable of accurately measuring the thermal conductivity of solid and molten compounds from room temperature up to 800 °C. By operating in the frequency-domain, we can lock into the harmonic thermal response of the material and reject the influence of ambient temperature fluctuations, and we can keep the probed volume below 1 µl to minimize convection. The design of the microfabricated hot-wire sensor, electrical systems, and insulating wire coating to protect against corrosion is covered in detail. Furthermore, we discuss the development of a full three-dimensional multilayer thermal model that accounts for both radial conduction into the sample and axial conduction along the wire and the effect of wire coatings. The 3D, multilayer model facilitates the measurement of small sample volumes important for material development. A sensitivity analysis and an error propagation calculation of the frequency-domain thermal model are performed to demonstrate what factors are most important for thermal conductivity measurements. Finally, we show thermal conductivity measurements including model data fitting on gas (argon), solid (sulfur), and molten substances over a range of temperatures.

Wild microorganism and plankton decay in ballast water treatments by solar disinfection (SODIS) and advanced oxidation processes.

Ballast water (BW) is a dead weight used by ships to provide stability in their journeys. It poses health, economic and ecological problems. Since 2017, the International Maritime Organization-IMO mandated management of BW. This research compares plankton mortality and microorganism inactivation in different BW treatments to identify possible decay models. Treatments include solar radiation (Srad), UV, H2O2 and advanced oxidation processes (AOPs). In the wild populations, the disinfection capacity was measured in natural seawater pumped from the Santa Marta port zone in Colombia. AOPs showed different models and effectiveness according to the treatment and microorganism. Plankton larger than 50 µm was the most resistant; therefore, it must be removed first by a previous filter. Wild microorganisms showed log-linear and log-linear tail decay models for most AOPs in E. coli. For Vibrio, the models were log-lineal tail and biphasic models.

Ultrafast laser welding of ceramics.

Welding of ceramics is a key missing component in modern manufacturing. Current methods cannot join ceramics in proximity to temperature-sensitive materials like polymers and electronic components. We introduce an ultrafast pulsed laser welding approach that relies on focusing light on interfaces to ensure an optical interaction volume in ceramics to stimulate nonlinear absorption processes, causing localized melting rather than ablation. The key is the interplay between linear and nonlinear optical properties and laser energy-material coupling. The welded ceramic assemblies hold high vacuum and have shear strengths comparable to metal-to-ceramic diffusion bonds. Laser welding can make ceramics integral components in devices for harsh environments as well as in optoelectronic and/or electronic packages needing visible-radio frequency transparency.

Caring for parents: an evolutionary rationale.

BACKGROUND: The evolutionary roots of human moral behavior are a key precondition to understanding human nature. Investigations usually start with a social dilemma and end up with a norm that can provide some insight into the origin of morality. We take the opposite direction by investigating whether the cultural norm that promotes helping parents and which is respected in different variants across cultures and is codified in several religions can spread through Darwinian competition. RESULTS: We show with a novel demographic model that the biological rule "During your reproductive period, give some of your resources to your post-fertile parents" will spread even if the cost of support given to post-fertile grandmothers considerably decreases the demographic parameters of fertile parents but radically increases the survival rate of grandchildren. The teaching of vital cultural content is likely to have been critical in making grandparental service valuable. We name this the Fifth Rule, after the Fifth Commandment that codifies such behaviors in Christianity. CONCLUSIONS: Selection for such behavior may have produced an innate moral tendency to honor parents even in situations, such as those experienced today, when the quantitative conditions would not necessarily favor the maintenance of this trait.

Ecological monitoring in a discrete-time prey-predator model.

The paper is aimed at the methodological development of ecological monitoring in discrete-time dynamic models. In earlier papers, in the framework of continuous-time models, we have shown how a systems-theoretical methodology can be applied to the monitoring of the state process of a system of interacting populations, also estimating certain abiotic environmental changes such as pollution, climatic or seasonal changes. In practice, however, there may be good reasons to use discrete-time models. (For instance, there may be discrete cycles in the development of the populations, or observations can be made only at discrete time steps.) Therefore the present paper is devoted to the development of the monitoring methodology in the framework of discrete-time models of population ecology. By monitoring we mean that, observing only certain component(s) of the system, we reconstruct the whole state process. This may be necessary, e.g., when in a complex ecosystem the observation of the densities of certain species is impossible, or too expensive. For the first presentation of the offered methodology, we have chosen a discrete-time version of the classical Lotka-Volterra prey-predator model. This is a minimal but not trivial system where the methodology can still be presented. We also show how this methodology can be applied to estimate the effect of an abiotic environmental change, using a component of the population system as an environmental indicator. Although this approach is illustrated in a simplest possible case, it can be easily extended to larger ecosystems with several interacting populations and different types of abiotic environmental effects.

Fuelling the mechanisms of asthma: Increased fatty acid oxidation in inflammatory immune cells may represent a novel therapeutic target.

BACKGROUND: Increasing evidence has shown the close link between energy metabolism and the differentiation, function, and longevity of immune cells. Chronic inflammatory conditions such as parasitic infections and cancer trigger a metabolic reprogramming from the preferential use of glucose to the up-regulation of fatty acid oxidation (FAO) in myeloid cells, including macrophages and granulocytic and monocytic myeloid-derived suppressor cells. Asthma is a chronic inflammatory condition where macrophages, eosinophils, and polymorphonuclear cells play an important role in its pathophysiology. OBJECTIVE: We tested whether FAO might play a role in the development of asthma-like traits and whether the inhibition of this metabolic pathway could represent a novel therapeutic approach. METHODS: OVA- and house dust mite (HDM)-induced murine asthma models were used in this study. RESULTS: Key FAO enzymes were significantly increased in the bronchial epithelium and inflammatory immune cells infiltrating the respiratory epithelium of mice exposed to OVA or HDM. Pharmacologic inhibition of FAO significantly decreased allergen-induced airway hyperresponsiveness, decreased the number of inflammatory cells, and reduced the production of cytokines and chemokines associated with asthma. CONCLUSIONS AND CLINICAL RELEVANCE: These novel observations suggest that allergic airway inflammation increases FAO in inflammatory cells to support the production of cytokines, chemokines, and other factors important in the development of asthma. Inhibition of FAO by re-purposing existing drugs approved for the treatment of heart disease may provide a novel therapeutic approach for the treatment of asthma.

[Training in laparoscopy and appendicitis]. / Entrenamiento en laparoscopia y apendicitis.

BACKGROUND: In order to improve laparoscopic skills, appendectomy is the most common procedure because of its high frequency and low difficulty. In spite of that, during the learning curve (each surgeon´s first 35 interventions) the incidence of complications may increase, so improvement in training means a bigger risk for some patients. METHODS: We retrospectively reviewed major complications (intra-abdominal abscess, intestinal occlusion, hemorrhage) of 1,710 appendectomies performed at our service between 1997 and 2013. We divided them in three groups: open appendectomy (OA, n= 1,258), laparoscopic appendectomy during the learning curve (LDC, n= 154) and laparoscopic appendectomy after the learning curve (LAC, n= 298). In addition, we distinguish between simple appendicitis (n= 1,233) and peritonitis (n= 477). RESULTS: In the OA group we detected110/1,258 major complications (8.7%), 28/154 major complications (18.2%) in the LDC group and 19/298 (6.4%) in the LAC group (p<0.05 LDC vs OA and LAC). In the simple appendicitis group, we found 13/889 major complications (1.5%) in OA, 3/115 (2.6%) in LDC group and 2/229 (0.9%) in LAC group (p= ns LDC vs OA and LAC). In the peritonitis group, 97/369 (26.3%) major complications were found in OA group, 25/39 (64%) in LDC group and 17/69 (24.6%) in LAC group (p<0.05 LDC vs OA and LAC). CONCLUSIONS: Educational purpose laparoscopic appendectomy must be used in simple appendicitis cases.

INTRODUCCION: Para la formación en laparoscopia, la apendicectomía es la intervención más utilizada, por su alta frecuencia y, habitualmente, escasa dificultad. Sin embargo, durante la curva de aprendizaje (las primeras 35 intervenciones), el número de complicaciones puede aumentar, con lo que el beneficio de la formación se puede convertir en perjuicio para algunos pacientes. Por ello hemos revisado las complicaciones graves de las apendicectomías laparoscópicas realizadas en nuestro Servicio antes y después de la curva de aprendizaje y las hemos comparado entre sí y con las de las apendicectomías abiertas. MATERIAL Y METODOS: Se han revisado las complicaciones graves (abscesos intraabdominales, oclusiones, hemorragias, etc..) de las 1.710 apendicectomías realizadas en nuestro centro desde 1997 hasta 2013, divididas en tres grupos: abiertas (AA, n= 1.258), laparoscópicas durante la curva de aprendizaje (LDC, n= 154) y laparoscópicas tras la curva de aprendizaje (LTC, n= 298). Se han dividido en apendicitis simples (n= 1.233) y peritonitis (n= 477). RESULTADOS: En el grupo AA se detectaron 110/1.258 complicaciones graves (8,7%), en el grupo LDC 28/154 (18,2%) y en el grupo LTC, 19/298 (6,4%) (p<0,05 LDC vs AA y LTC). En las apendicitis simples las complicaciones fueron 13/889 (1,5%), en las AA 3/115 (2,6%) en el grupo LDC, y 2/229 en el grupo LTC (0,9%) (p= ns LDC vs AA y LTC). En las peritonitis las complicaciones fueron 97/369 (26,3%) en las AA, 25/39 (64%) en el grupo LDC y 17/69 (24,6%) en el grupo LTC (p>;0,05 LDC vs AA y LTC). CONCLUSIONES: La apendicectomía laparoscópica con fines formativos debería reservarse a los casos de apendicitis simples.

[Management of appendicular mass]. / Tratamiento y seguimiento del plastrón apendicular.

BACKGROUND: Management of appendicular mass is still controversial. Some authors plead for an initial non-operative approach followed by a delayed appendectomy. OBJECTIVES: Our aim has been to revise the usefulness of this management and the optimal time to carry out the appendectomy. METHODS: We made a retrospective review of all the appendicular mass cases treated in our hospital during the last 8 years. We analyzed the success rate of the non-operative approach, the interval until the delayed appendectomy was performed, difficulty found at surgery and the occurred complications. RESULTS: Our series includes 19 appendicular mass cases managed initially by a non-operative approach. Intravenous antibiotics were administered to all of them and in 14 cases a peritoneal drainage was placed (the average length of stay was of 11.5 days). In 3 cases (16%) early appendectomy was performed (12, 30 and 40 days after the onset of the symptoms). In 16 (84%) the conservative approach succeeded and the appendectomy was delayed 3-12 months (average: 6.6 months). Four of them were performed by an open approach and 12 by laparoscopy (in 3 of which conversion was needed). The average length of stay was of 1.8 days, with only one complication (wound abscess). Of these 16 delayed appendectomies, 11 were not technically difficult to perform (average wait of 5.5 months) and in 5 cases the procedure was difficult due to multiple adhesions (average wait of 9.4 months). CONCLUSION: Conservative management of appendicular mass is useful, with a success rate of 84% in our series. The appendectomy was less hazardous if performed 3-6 months after the onset of the symptoms.

Construction of new Pichia pastoris X-33 strains for production of lycopene and ß-carotene.

In this study, we used the non-carotenogenic yeast Pichia pastoris X33 as a receptor for ß-carotene-encoding genes, in order to obtain new recombinant strains capable of producing different carotenoidic compounds. We designed and constructed two plasmids, pGAPZA-EBI* and pGAPZA-EBI*L*, containing the genes encoding lycopene and ß-carotene, respectively. Plasmid pGAPZA-EBI*, expresses three genes, crtE, crtB, and crtI*, that encode three carotenogenic enzymes, geranylgeranyl diphosphate synthase, phytoene synthase, and phytoene desaturase, respectively. The other plasmid, pGAPZA-EBI*L*, carried not only the three genes above mentioned, but also the crtL* gene, that encodes lycopene ß-cyclase. The genes crtE, crtB, and crtI were obtained from Erwinia uredovora, whereas crtL* was cloned from Ficus carica (JF279547). The plasmids were integrated into P. pastoris genomic DNA, and the resulting clones Pp-EBI and Pp-EBIL were selected for either lycopene or ß-carotene production and purification, respectively. Cells of these strains were investigated for their carotenoid contents in YPD media. These carotenoids produced by the recombinant P. pastoris clones were qualitatively and quantitatively analyzed by high-resolution liquid chromatography, coupled to photodiode array detector. These analyses confirmed that the recombinant P. pastoris clones indeed produced either lycopene or ß-carotene, according to the integrated vector, and productions of 1.141 µg of lycopene and 339 µg of ß-carotene per gram of cells (dry weight) were achieved. To the best of our knowledge, this is the first time that P. pastoris has been genetically manipulated to produce ß-carotene, thus providing an alternative source for large-scale biosynthesis of carotenoids.

Knock in of the AKT1 E17K mutation in human breast epithelial cells does not recapitulate oncogenic PIK3CA mutations.

An oncogenic mutation (G49A:E17K) in the AKT1 gene has been described recently in human breast, colon, and ovarian cancers. The low frequency of this mutation and perhaps other selective pressures have prevented the isolation of human cancer cell lines that harbor this mutation thereby limiting functional analysis. Here, we create a physiologic in vitro model to study the effects of this mutation by using somatic cell gene targeting using the nontumorigenic human breast epithelial cell line, MCF10A. Surprisingly, knock in of E17K into the AKT1 gene had minimal phenotypic consequences and importantly, did not recapitulate the biochemical and growth characteristics seen with somatic cell knock in of PIK3CA hotspot mutations. These results suggest that mutations in critical genes within the PI3-kinase (PI3K) pathway are not functionally equivalent, and that other cooperative genetic events may be necessary to achieve oncogenic PI3K pathway activation in cancers that contain the AKT1 E17K mutation.

Application of change-point problem to the detection of plant patches.

In ecology, if the considered area or space is large, the spatial distribution of individuals of a given plant species is never homogeneous; plants form different patches. The homogeneity change in space or in time (in particular, the related change-point problem) is an important research subject in mathematical statistics. In the paper, for a given data system along a straight line, two areas are considered, where the data of each area come from different discrete distributions, with unknown parameters. In the paper a method is presented for the estimation of the distribution change-point between both areas and an estimate is given for the distributions separated by the obtained change-point. The solution of this problem will be based on the maximum likelihood method. Furthermore, based on an adaptation of the well-known bootstrap resampling, a method for the estimation of the so-called change-interval is also given. The latter approach is very general, since it not only applies in the case of the maximum-likelihood estimation of the change-point, but it can be also used starting from any other change-point estimation known in the ecological literature. The proposed model is validated against typical ecological situations, providing at the same time a verification of the applied algorithms.

Observation and control in a model of a cell population affected by radiation.

The effect of radiation on a cell population is described by a two-dimensional nonlinear system of differential equations. If the radiation rate is not too high, the system is known to have an asymptotically stable equilibrium. First, for the monitoring of this effect, the concept of observability is applied. For the case when the total number of cells is observed, without distinction between healthy and affected cells, a so-called observer system is constructed, which, at least near the equilibrium state, makes it possible to recover the dynamics of both the healthy and the affected cells, from the observation of the total number of cells without distinction. Results of simulations with illustrative data are also presented. If we want to control the system into a required new equilibrium state, and maintain this new equilibrium by a constant control, a technique of theory of optimal control can be applied to construct a feedback control system.

Interannual distribution of Pacific hake Merluccius productus larvae in the southern part of the California Current.

The interannual distribution of early life stages of Pacific hake Merluccius productus, within the southern part of the California Current (32-23 degrees N) from 1951 to 2001, was examined to describe the relationship between spawning habitat and environmental conditions. Mean annual abundance was affected by different factors along the west coast of the Baja California Peninsula. In the northern areas (Ensenada and Punta Baja), reduced abundance of larvae coincided with the El Niño and a North Pacific Ocean climatic regime shift, but in the southern areas (San Ignacio to Bahía Magdalena), the drastic reductions suggested a fishery effect for large adults of the coastal migratory population, starting in 1966. Two spawning stocks, coastal and dwarf, were evident in comparisons of latitudinal differences in occurrence of early stages and differences in temperature preferences that seemed to break at Punta Eugenia.

[Laparoscopic appendectomy after the learning curve]. / La apendicectomía laparoscópica más allá de la curva de aprendizaje.

BACKGROUND: Despite its increasing popularity, laparoscopic appendectomy does not put an unanimous end to the answer to the best treatment for appendicitis. Although the postoperative stay is shorter, the wound infection practically does not exist and scars are minimal, some publications question its advantages due to the incidence of intra-abdominal absceses, postoperative analgesia requirements and the recently described "postlaparoscopic appendectomy complication" (PLAC), an intra-abdominal infection, without abscess formation, which develops after laparoscopic appendectomy for non-complicated appendicitis. Some of this series include the "learning curve", wherein they compare results of inexperienced surgeons in laparoscopic techniques with those obtained after with the firmly established open appendectomy (OA) technique. With the aim to clarify this aspects, we reviewed our experience in laparoscopic appendectomy during (LDC) and after (LAC) the "learning curve" and we compared their complications with the open appendectomies' ones. METHODS: We retrospectively reviewed 807 appendectomies: 208 laparoscopic (LA) and 599 open (OA) from January 2001 to December 2007 performed in our hospital. In the laparoscopic group, 83 of them (40%) were done during the learning curve (each surgeon's 35 first interventions, LDC) and 125 (60%) after the learning curve (LAC). We have compared both laparoscopic subgroups to each other and to the open appendectomies group. We analysed the age, sex, length of stay, kind of appendicitis (simple or perforated appendicitis) and five of the most serious complications: intra-abdominal abscess, postoperative intestinal occlusion, intestinal perforation, haemorrhage and PLAC. RESULTS: The mean age (9 years), sex (58% men; 42% women) and the peritonitis rate (30%) were similar among the 3 groups. The mean length of stay was reduced from 5.4 days in OA group to 4.2 days in LA group and 3.6 days in LAC group (p < 0.01). The simple appendicitis cases had the shortest length of stay: 3.41 days in OA group and 2.16 days in LA group (p < 0.0001). There were no differences in stay for the peritonitis group. In the OA group, we detected 56 severe complications (9,3%): 49 abcesses, 2 occlusions, 2 PLAC, 1 haemorrhage, 1 intestinal perforation and 1 liver abscess. Nineteen severe complications were found in LDC group (22,9%): 9 abscesses, 4 occlusions, 4 haemorrhages, 1 intestinal perforation and 1 PLAC (p < 0.01 vs OA group). In the LAC group, we found 13 complications (10,4%): 9 abscesses, 1 occlusion, 1 PLAC and 2 haemorrhages (p = 0.3 vs OA group). CONCLUSIONS: 1. The length of stay was significantly reduced in laparoscopic appendectomies. 2. Severe complications, particularly intestinal occlusions and haemorrhages, increased significantly during the learning curve, with a slight fluctuation for intra-abdominal abscesses and PLAC. 3. After the learning curve, complications' global rate was similar to the OA group's, with an increment of haemorrhages and occlusions, no variation for PLAC and a slight reduction for intra-abdominal abscesses. 4. In our experience, laparoscopic appendectomy after the learning curve is the best therapeutic option for acute appendicitis.

Prosaposin is an AR-target gene and its neurotrophic domain upregulates AR expression and activity in prostate stromal cells.

Recent studies have introduced prosaposin (PSAP) as a pleiotrophic growth factor for prostate cancer (PCa). We have previously reported that PSAP or one of its known active molecular derivatives, saposin C functions as an androgen-agonist and androgen-regulated gene (ARG) for androgen-sensitive (AS) PCa cell lines. Due to the potential significance of androgen receptor (AR)-expressing stroma in PCa, we evaluated a possible bi-directional paracrine regulatory interactions between DHT and PSAP in AR-positive prostate stromal (PrSt) cells. We report that saposin C in a ligand-independent manner increased AR expression, its nuclear content, and tyrosine phosphorylation. DHT treatment of PrSt cells increased PSAP expression. We also demonstrated both serum- and androgen-inducibility of a previously characterized hormone-responsive element (HRE) located in the proximal region of PSAP promoter. In addition, conditioned-media derived from PrSt cells and bone fibroblasts (i.e., MSF) differentially increased PSAP-promoter activity in androgen-independent (AI) PC-3 and AS LNCaP cells. Our data for the first time demonstrate that not only saposin C or PSAP regulates AR expression/activity, but also function as an ARG in PrSt. Ligand-independent activation of AR by PSAP or saposin C in PCa and stromal cells may contribute not only to prostate carcinogenesis at an early stage, but also in AI progression of the disease in an androgen-deprived tumor microenvironment.

Understanding, compliance and psychological impact of the SARS quarantine experience.

This study examines a cohort of persons quarantined during the 2003 SARS outbreak in Canada and describes their understanding of, difficulties and compliance with, and the psychological impact of the quarantine experience. A mailed questionnaire was administered to 1912 eligible adults and included the Impact of Events Scale - Revised (IES-R) to assess symptoms of post-traumatic stress disorder (PTSD). Self-reported compliance with all required quarantine measures was low (15.8+/-2.3%), although significantly higher when the rationale for quarantine was understood (P=0.018). Health-care workers (HCW) experienced greater psychological distress, including symptoms of PTSD (P<0.001). Increasing perceived difficulty with compliance, HCW, longer quarantine and compliance with quarantine requirements were significant contributors to higher IES-R scores. The low compliance with quarantine requirements introduces concerns about the effectiveness of quarantine as a public health measure. Improvements in compliance and reduced psychological distress may be possible by minimizing duration, revising requirements, and providing enhanced education and support.

Use of an interferon-gamma based assay to assess bladder cancer patients treated with intravesical BCG and exposed to tuberculosis.

OBJECTIVE: Compare the QuantiFERON-TB Gold In-Tube (QFT) assay and the tuberculin skin test (TST) in bladder cancer patients receiving high dose BCG therapy (BCG patients). DESIGN AND METHODS: BCG patients and healthy visitors, both exposed to tuberculosis, were screened with a TST and QFT. RESULTS: QFT-TST correlation was excellent in visitors, but poor in BCG patients. BCG therapy predicted a positive TST (p<0.001) but not a positive QFT (p=0.35). DISCUSSION: The management of BCG patients was impacted, by measuring the QFT.