Advances in the Structural Strategies of the Self-Assembly of Photoresponsive Supramolecular Systems.

Photosensitive supramolecular systems have garnered attention due to their potential to catalyze highly specific tasks through structural changes triggered by a light stimulus. The tunability of their chemical structure and charge transfer properties provides opportunities for designing and developing smart materials for multidisciplinary applications. This review focuses on the approaches reported in the literature for tailoring properties of the photosensitive supramolecular systems, including MOFs, MOPs, and HOFs. We discuss relevant aspects regarding their chemical structure, action mechanisms, design principles, applications, and future perspectives.

ACE activity and endurance performance during the South African Ironman triathlons.

The insertion allele of the angiotensin-converting enzyme (ACE) gene has been associated with endurance performance. Since a large portion of the variance seen in circulatory ACE levels is unaccounted for by the insertion/deletion polymorphism it is likely that the ACE phenotype would serve as a more informative marker in assessing elite endurance performance. The aim of this study was to correlate plasma ACE activity with performance of a homogenous population of South African-born Caucasian male triathletes. Plasma ACE activity was determined in 145 triathletes, representing the fastest and slowest subgroups who completed either the 2000 or 2001 South African Ironman Triathlon. There was a trend for lower mean plasma ACE activity in the fastest (28.85±8.60 mU/ml) when compared to the slowest finisher subgroup (31.65±8.75 mU/ml, P=0.055). There was a significant positive correlation between plasma ACE activity and overall finishing time within the participants who completed the event in under 15 h (r=0.192, P=0.029). There was also a positive correlation with cycle (r=0.195, P=0.034) and run (r=0.184, P=0.040) stages but not the swim stage (r=0.084, P=0.353). In conclusion, this is the first study to report a relationship between plasma ACE activity and endurance performance in humans.

A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis.

Hereditary haemochromatosis (HH), which affects some 1 in 400 and has an estimated carrier frequency of 1 in 10 individuals of Northern European descent, results in multi-organ dysfunction caused by increased iron deposition, and is treatable if detected early. Using linkage-disequilibrium and full haplotype analysis, we have identified a 250-kilobase region more than 3 megabases telomeric of the major histocompatibility complex (MHC) that is identical-by-descent in 85% of patient chromosomes. Within this region, we have identified a gene related to the MHC class I family, termed HLA-H, containing two missense alterations. One of these is predicted to inactivate this class of proteins and was found homozygous in 83% of 178 patients. A role of this gene in haemochromatosis is supported by the frequency and nature of the major mutation and prior studies implicating MHC class I-like proteins in iron metabolism.

[Ecographic viewing and prenatal diagnosis of infradiaphragmatic total anomalous pulmonary venous drainage: report of a case]. / Visualización ecográfica y diagnóstico prenatal de drenaje venoso pulmonar anómalo total infradiafragmático: a propósito de un caso.

Anomalous pulmonary venous connection is a rare pathology, both partial and total forms, according to the number of pulmonary veins draining into the left atrium, respectively. Total forms are classified into four groups, depending upon the anomalous connections to the systemic veins: supra, intracardiac or below, and finally a mixed form, the less frequent. Prenatal, even postnatal diagnose is difficult, especially in partial isolated forms. The association with chromosomal abnormalities is low, however is highly associated with complex heart malformations, especially total forms, often in the context of heterotaxy syndromes. We present a case of infracardiac APVC, in the context of complex heart disease, associated with complete atrioventricular canal and conotruncal anomaly, that came to surgery at 48 hours of life with poor outcome. We described the ultrasound and magnetic resonance angiography of this anomaly and its perinatal prognosis and management.

Enhancing Solid-Phase Extraction of Tamoxifen and Its Metabolites from Human Plasma Using MOF-Integrated Polyacrylonitrile Composites: A Study on CuBTC and ZIF-8 Efficacy.

This study investigates electrospun fibers of metal-organic frameworks (MOFs), particularly CuBTC and ZIF-8, in polyacrylonitrile (PAN) for the solid-phase extraction (SPE) of Tamoxifen (TAM) and its metabolites (NDTAM, ENDO, and 4OHT) from human blood plasma. The focus is on the isolation, pre-concentration, and extraction of the analytes, aiming to provide a more accessible and affordable breast cancer patient-monitoring technology. The unique physicochemical properties of MOFs, such as high porosity and surface area, combined with PAN's stability and low density, are leveraged to improve SPE efficiency. The study meticulously examines the interactions of these MOFs with the analytes under various conditions, including elution solvents and protein precipitators. Results reveal that ZIF-8/PAN composites outperform CuBTC/PAN and PAN alone, especially when methanol is used as the protein precipitator. This superior performance is attributed to the physicochemical compatibility between the analytes' properties, like solubility and polarity, and the MOFs' structural features, including pore flexibility, active site availability, surface polarity, and surface area. The findings underscore MOFs' potential in SPE applications and provide valuable insights into the selectivity and sensitivity of different MOFs towards specific analytes, advancing more efficient targeted extraction methods in biomedical analysis.

Paper and Other Fibrous Materials-A Complete Platform for Biosensing Applications.

Paper-based analytical devices (PADs) and Electrospun Fiber-Based Biosensors (EFBs) have aroused the interest of the academy and industry due to their affordability, sensitivity, ease of use, robustness, being equipment-free, and deliverability to end-users. These features make them suitable to face the need for point-of-care (POC) diagnostics, monitoring, environmental, and quality food control applications. Our work introduces new and experienced researchers in the field to a practical guide for fibrous-based biosensors fabrication with insight into the chemical and physical interaction of fibrous materials with a wide variety of materials for functionalization and biofunctionalization purposes. This research also allows readers to compare classical and novel materials, fabrication techniques, immobilization methods, signal transduction, and readout. Moreover, the examined classical and alternative mathematical models provide a powerful tool for bioanalytical device designing for the multiple steps required in biosensing platforms. Finally, we aimed this research to comprise the current state of PADs and EFBs research and their future direction to offer the reader a full insight on this topic.

Clinical experience with miglustat therapy in pediatric patients with Niemann-Pick disease type C: a case series.

Niemann-Pick disease type C (NP-C) is an inherited neurovisceral lysosomal lipid storage disease characterized by progressive neurological deterioration. Different clinical forms have been defined based on patient age at onset: perinatal, early-infantile (EI), late-infantile (Li), juvenile and adult. We evaluated the efficacy and tolerability of miglustat in 16 symptomatic NP-C patients, with comparative reference to one neurologically asymptomatic, untreated patient. All patients were categorized according to age at neurological disease onset, and were assessed using a standardized clinical assessment protocol: disability and cognitive function scales, positron emission tomography (PET), and biochemical markers. PET and disability scale evaluations indicated that cerebral hypometabolism and neurological symptoms were stabilized during treatment in juvenile-onset NP-C patients. EI and Li NP-C patients, who had higher disease severity at baseline (treatment start), showed increased disability scores and progressive cerebral hypometabolism during follow up. Similarly, while cognitive scale scores remained relatively stable in patients with juvenile NP-C, cognition deteriorated in EI and Li patients. Plasma chitotriosidase (ChT) activity was lower in the juvenile NP-C subgroup than in EI and Li patients, and generally increased in patients who discontinued treatment. Plasma CCL18/PARC and ChT activities indicated greater macrophagic activity in EI and Li patients versus juveniles. Miglustat was generally well tolerated; frequent adverse events included diarrhea and flatulence, which were managed effectively by dietary modification and loperamide. Overall, miglustat appeared to stabilize neurological status in juvenile-onset NP-C patients, but therapeutic benefits appeared smaller among younger patients who were at a more advanced stage of disease at baseline.

Tailoring the Diameters of Electro-Mechanically Spun Fibers by Controlling Their Deborah Numbers.

Polymer solutions with different concentrations of SU-8 2002/poly(ethylene) glycol/tetrabutyl ammonium tetrafluoroborate (SU-8/PEO/TBATFB) were electrospun in a low-voltage near-field electrospinning platform (LVNFES) at different velocities. Their diameters were related to the concentration contents as well as to their Deborah (De) numbers, which describes the elasticity of the polymer solution under determined operating conditions. We found a direct correlation between the concentration of PEO/TBATFB, the De and the diameter of the fibers. Fibers with diameters as thin as 465 nm can be achieved for De ≈ 1.

Quantitative assessment of biosecurity in broiler farms using Biocheck.UGent in Central Luzon, Philippines.

The biosecurity status of 397 broiler farms in Central Luzon, the highest poultry meat-producing region in the Philippines, was assessed using Biocheck.Ugent. This online biosecurity assessment tool quantifies biosecurity level or compliance of surveyed farms. The system generates scores that reflect the current biosecurity status of each farm in terms of the different external and internal biosecurity measures being implemented in each farm. It was initially developed for pigs and broilers but recently is available for layers, swine, and cattle (beef, dairy, and veal). The overall biosecurity score of broiler farms in Central Luzon was 71.2%, with average external and internal biosecurity scores of 68.5 and 77.2%, respectively. Bataan had the highest biosecurity scores (76.5%) compared with the other 6 provinces. This was also true for the external and internal biosecurity scores of the province, with mean scores of 72.1 and 80.1%, respectively. Of the 11 subcategories of external and internal biosecurity that were assessed, purchase of day-old chicks, feeds and water supply, supply of materials, cleaning and disinfection, and materials between compartments had scores higher than the global scores. Low scores were generated from transport of live animals and infrastructure and biological vectors. The mean biosecurity score of farms with traditional/conventional type of housing was 7.8% lower than that with tunnel vent housing. Every year as the farm gets older, there was a corresponding drop of 0.2% in the biosecurity score. Biosecurity measures are in place in broiler farms in the country. However, there were areas with low scores which need to be prioritized to improve and upgrade the farms' biosecurity status. To date, this is the first quantitative assessment of biosecurity in broiler farms in the Philippines. High biosecurity scores may entail greater protection from disease incursion.

Biosecurity assessment of layer farms in Central Luzon, Philippines.

Biosecurity assessment in poultry farms is important for disease prevention and control. When specific biosecurity measures are assessed, they become more useful if they are quantified. While there are qualitative means to assess biosecurity, specific improvements can be implemented easily when compliance to biosecurity measures are quantified. To quantify biosecurity measures in 124 layer farms in Central Luzon, a survey was carried out using a modified Biocheck.UGent biosecurity scoring system. The study revealed that external and internal biosecurity scores among layer farms in Central Luzon were widely spread out suggesting that compliance to various biosecurity measures differed from farm to farm. This further suggests that layer farms need to improve their biosecurity practices. The overall biosecurity score of layer farms in the region is 65.9 % while the total regional scores for external and internal biosecurity are 63.3 % and 71.9 %, respectively. Bulacan had the highest overall biosecurity across provinces which was followed by Bataan. The two highest mean external biosecurity scores were those of the subcategories, supply of materials (mean = 87.1) and purchase of pullets (mean = 83.7) while the lowest was that of the category, transport of animals (mean = 50.6). In the internal biosecurity category, materials and measures between compartments had the highest mean score. Low to negligible correlations between external and internal biosecurity were seen among layer farms except for the province of Tarlac. This suggests that a farm with low external biosecurity score also had low internal biosecurity score while high external biosecurity score was equated to high internal biosecurity score. Analysis also showed that large commercials farms had biosecurity ratings that were 6.84 higher compared to small commercial farms. Results of this study may be beneficial for farmers to make necessary improvement to increase level of compliance to biosecurity measures. Policies to impose, implement and monitor compliance may also be instituted.

Neuroimaging Advances in Deep Brain Stimulation: Review of Indications, Anatomy, and Brain Connectomics.

Deep brain stimulation is an established therapy for multiple brain disorders, with rapidly expanding potential indications. Neuroimaging has advanced the field of deep brain stimulation through improvements in delineation of anatomy, and, more recently, application of brain connectomics. Older lesion-derived, localizationist theories of these conditions have evolved to newer, network-based "circuitopathies," aided by the ability to directly assess these brain circuits in vivo through the use of advanced neuroimaging techniques, such as diffusion tractography and fMRI. In this review, we use a combination of ultra-high-field MR imaging and diffusion tractography to highlight relevant anatomy for the currently approved indications for deep brain stimulation in the United States: essential tremor, Parkinson disease, drug-resistant epilepsy, dystonia, and obsessive-compulsive disorder. We also review the literature regarding the use of fMRI and diffusion tractography in understanding the role of deep brain stimulation in these disorders, as well as their potential use in both surgical targeting and device programming.

A palaeolithic map from 13,660 calBP: engraved stone blocks from the Late Magdalenian in Abauntz Cave (Navarra, Spain).

An engraved block from the cave of Abauntz is interpreted as a Magdalenian map in which the actual surrounding landscape, including mountains, rivers, and ponds, is represented. Some possible routes or avenues of access to different parts of the geography are also engraved on the landscape. The engraving seems to reproduce the meandering course of a river crossing the upper part of side A of the block, joined by two tributaries near two mountains. One of these is identical to the mountain that can be seen from the cave, with herds of ibex depicted on its hillsides, on both sides of the gorge in front of which the cave of Abauntz is strategically located. In the southern part of the gorge, there is a completely flat area where the watercourses slow down, forming meanders and flooding in springtime. The following elements are also represented on the block: tangles of concentric strokes and bundles of lines forming very marked meanders. In short, all of these engravings could be a sketch or a simple map of the area around the cave. It could represent the plan for a coming hunt or perhaps a narrative story of one that had already happened. This paper is provided in the context of recent discussions on early modern human capacities of spatial awareness, planning, and organized hunting.

Bismuth recovery from acidic solutions using Cyphos IL-101 immobilized in a composite biopolymer matrix.

Impregnated resins prepared by the immobilization of an ionic liquid (IL, Cyphos IL-101, tetradecyl(trihexyl)phosphonium chloride) into a composite biopolymer matrix (made of gelatin and alginate) have been tested for recovery of Bi(III) from acidic solutions. The concentration of HCl slightly influenced Bi(III) sorption capacity. Bismuth(III) sorption capacity increased with IL content in the resin but non-linearly. Maximum sorption capacity reached 110-130mgBig(-1) in 1M HCl solutions. The mechanism involved in Bi recovery was probably an ion exchange mechanism, though it was not possible to establish the stoichiometric exchange ratio between BiCl(4)(-) and IL. Sorption kinetics were investigated through the evaluation of a series of parameters: metal concentration, sorbent dosage, type and size of sorbent particles and agitation speed. In order to reinforce the stability of the resin particles, the IL-encapsulated gels were dried; this may cause a reduction in the porosity of the resin particle and then diffusion limitations. The intraparticle diffusion coefficients were evaluated using the Crank's equation. Additionally, the pseudo-first-order and pseudo-second-order equations were systematically tested on sorption kinetics. Metal can be desorbed from loaded resins using either citric acid or KI/HCl solutions. The sorbent could be recycled for at least three sorption/desorption cycles.

The clinical value of biomarkers in respiratory complications in hematopoietic SCT.

To determine the role of biomarkers in the clinical management of respiratory complications (RC) in hematopoietic stem cell transplantation (HSCT) recipients, we have prospectively evaluated a cohort of 175 patients followed-up for 1 year after HSCT. To avoid misinterpretation, we have excluded both unidentified respiratory infections (RI) and mixed RI. A total of 64 RC were included. Plasma levels of C-reactive protein (CRP), procalcitonin (PCT) and proadrenomedullin (proADM) were measured at diagnosis and on day 3 and 7. Different cytokines were evaluated in serum on the first day. No HSCT recipients without RC were included as a control group. Compared with RI, non-infectious RC showed a significant increase in CRP, proADM and interleukin 6 on day 0 (P=0.005; P=0.03 and P=0.04, respectively). When only RI were considered, we observed that bacterial-fungal PI showed higher levels of CRP (P=0.02), PCT (P=0.04) and proADM (P<0.01). Persistent low levels of proADM biomarkers suggest viral infection (specificity and positive predictive value 100%). Patients dying of RC had PCT and proADM levels higher than survivors (P=0.002 and P=0.03, respectively). In HSCT recipients biomarkers increase in both infectious and non-infectious RC. They may have utility in the assessment of the severity of RC and in suspecting a viral etiology.

cDNA cloning and characterization of A3i, an alternatively spliced rat A3 adenosine receptor variant.

A cDNA encoding variant form of the A3 adenosine (Ado) receptor was isolated from rat by reverse transcription of brain mRNA followed by PCR. The full-length receptor (A3i) cDNA encodes 337 amino acids and shares complete sequence identity with the rat A3 Ado receptor, except for the presence of a seventeen amino acid insert located in the second intracellular domain. In contrast to the rat A3 receptor, stable expression of A3i in CHO cells resulted in poor coupling to Gi proteins. Analysis of receptor transcripts by RT-PCR suggests that the A3 Ado receptor mRNAs are products of alternative splicing. Sequence analysis of A3 genomic DNA identified a 1.7 kb intron that is likely alternatively spliced to produce the A3 and A3i receptors.

Oral delivery of antibodies. Future pharmacokinetic trends.

Antibodies have been investigated as specific targeting agents for cancer diagnosis and therapy, to inactivate toxic substances including drugs and also as passive immunotherapy for neoplastic or infectious diseases. In most cases the antibodies were administered systemically by the intravenous route. More recently, however, there has been increasing interest in the oral administration of antibodies for localised treatment of infections or other conditions in the gastrointestinal tract. The normal physiological handling of ingested proteins is degradation by proteases in the stomach and intestine into small peptides or amino acids which are subsequently absorbed. Proteolytic enzymes involved in the degradation of orally administered immunoglobulins include pepsin, trypsin, chymotrypsin, carboxypeptidase and elastase. These enzymes initially degrade the antibodies to F(ab')2. Fab and Fc fragments. The F(ab')2 and Fab fragments, however, retain some of their neutralising activity locally in the gastrointestinal tract. Various approaches are possible to increase the stability of orally administered antibodies against proteolysis, including formulation in liposomes, coating with polymers and genetic engineering of resistant forms. The clinical application of orally administered antibodies includes the treatment and prevention of gastrointestinal infections caused by enteric pathogens such as rotavirus, Escherichia coli or Vibrio cholerae in susceptible individuals including those with immunodeficiency diseases and patients with bone marrow transplants. There is also a suggestion that such agents may be useful in preventing chemotherapy-induced gastrointestinal mucositis. Future opportunities for research include the design of oral dosage forms of antibodies which resist proteolysis and can deliver a greater fraction of immunoreactive antibody locally in the gastrointestinal tract for the treatment of infections or perhaps even to allow the absorption of antibodies for the treatment or prevention of systemic conditions.

Tracheoesophageal fistula, gastrointestinal abnormalities, hypospadias, and prenatal growth deficiency.

We studied 2 sibs, born to consanguineous parents, who presented with an MCA pattern which includes low birthweight, tracheoesophageal fistula, duodenal atresia, extrahepatic biliary atresia, hypoplastic pancreas, and hypospadias. This constellation of congenital anomalies appears to be a previously unreported autosomal recessive syndrome. A computerized search of the data files of the Spanish Collaborative Study of Congenital Malformations (ECEMC) identified 3 other unrelated infants with intestinal atresias, hypospadias, and low birth weight. These cases may represent a milder expression of the same syndrome.

The Rhino-Probe nasal curette for detecting respiratory syncytial virus in children.

During two outbreaks of respiratory syncytial virus (RSV) infection, 68 children with acute respiratory illnesses were cultured for RSV using a Rhino-Probe (RP) nasal curette and either a nasopharyngeal (NP) swab or a nasal wash (NW). In the first outbreak isolations of RSV by the RP nasal curette and NP swab methods were compared. RSV was cultured from 25 of 42 (60%) subjects using the RP nasal curette and from 20 of 42 (48%) subjects using the NP swab. In the second outbreak the RP nasal curette and the NW collection techniques were compared. RSV was isolated from 15 of 26 (58%) children evaluated. RSV was cultured from 14 of 15 (93%) patients by RP and 13 of 15 (87%) when using NW. In the group of culture-positive subjects, the TESTPACK RSV rapid antigen test was positive in 10 of 15 (67%) using the RP and in 6 of 15 (40%) using the NW. Like the NP swab the RP nasal curette was simple, noninvasive and relatively inexpensive, yet it was as sensitive as the NW for detection of RSV.

Interaction of cobalt ions with carboxypeptidase A.

The interaction of cobalt(II) with native and cobalt(II)-substituted carboxypeptidase has been investigated, at pH 7.5, by electronic absorption and 1H NMR spectroscopies. The reaction of the cobalt(II) uptake by the metalloenzyme [MCPA] (M = Zn or Co) occurs very slowly and a bimetallic complex, [MCPA(Co)], is formed. On the basis of the 1H NOE experiments, the isotropically shifted proton resonances were assigned as belonging to a coordinated histidine residue. 1H NMR titrations of [ZnCPA(Co)] with zinc(II) show that the zinc ion does not compete with cobalt for binding to the noncatalytic site. The temperature dependence of the isotropic shifts, molar absorbance, and longitudinal relaxation time values are indicative of a five-coordinated geometry for the cobalt ion. The identification of the noncatalytic cobalt binding site is also discussed.

Pre-targeted radioimmunotherapy of human colon cancer xenografts in athymic mice using streptavidin-CC49 monoclonal antibody and 90Y-DOTA-biotin.

Radioimmunotherapy of solid malignancies using directly labelled 90Y-monoclonal antibodies has been associated in clinical trials with dose-limiting bone marrow toxicity. Our objective in this study was to evaluate the efficacy and toxicity of an alternative two-step pre-targeted radioimmunotherapy protocol for the treatment of human colon cancer. The two-step protocol consisted of administration of the tumour-associated glycoprotein (TAG-72) monoclonal antibody CC49 conjugated to streptavidin, followed by administration of 90Y-DOTA-biotin. Swiss nu/nu athymic mice bearing subcutaneous LS174T human colon cancer xenografts were injected intraperitoneally with streptavidin-CC49 (250 micrograms), followed 40 h later by an intravenous injection of 90Y-DOTA-biotin (900 microCi, 40 micrograms). Tumour growth was measured over 25 days and compared with that in control mice receiving no treatment. Bone marrow and normal tissue toxicity was determined by peripheral blood leucocyte counts and by monitoring the body weight of the animals. Pre-targeted radioimmunotherapy resulted in a modest (30-40%) decrease in the mean tumour growth rate in treated mice compared to control animals. There was no change in body weight following treatment and peripheral blood leucocyte counts remained within the normal range. Pre-targeted radioimmunotherapy was safe at administered amounts of 90Y radioactivity, which were at least nine-fold higher than those previously determined to be lethal using directly labelled 90Y-monoclonal antibodies. The results of this study are promising for the application of pre-targeted radioimmunotherapy using streptavidin-CC49 and 90Y-DOTA-biotin for the treatment of advanced colorectal cancer in humans.