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This report presents a case of ring chromosome 7 syndrome with bilateral cleft lip and palate. A four-year-old boy presented with bilateral cleft lip and palate, microcephaly, clenched toes, cafe-au-lait spots, a history of epilepsy, and severe intellectual disability. Genetic karyotyping revealed 46 XY r(7) (p22q36). His cheiloplasty and delayed palatoplasty were successful. A review of 22 previous r(7) patients revealed that 22.7% had cleft lip and/or palate. This case demonstrates the importance of a multidisciplinary evaluation for cleft patients, particularly those with syndromic features and global developmental delay.

Western Eurasia witnessed several large-scale human migrations during the Holocene1–5. Here, to investigate the cross-continental effects of these migrations, we shotgun-sequenced 317 genomes—mainly from the Mesolithic and Neolithic periods—from across northern and western Eurasia. These were imputed alongside published data to obtain diploid genotypes from more than 1,600 ancient humans. Our analyses revealed a ‘great divide’ genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers were highly genetically differentiated east and west of this zone, and the effect of the neolithization was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacement of hunter-gatherers in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, whereas, east of the Urals, relatedness remained high until around 4,000 bp, consistent with the persistence of localized groups of hunter-gatherers. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 bp, resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive, but we show that hunter-gatherers from the Middle Don region contributed ancestry to them. Yamnaya groups later admixed with individuals associated with the Globular Amphora culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a ‘Neolithic steppe’ cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

ABSTRACT:There is limited experimental evidence on the effects of large-scale, government-led interventions on human capital in resource-constrained settings. We report results from a randomized trial of the government of Ghana's school feeding. After two years, the program led to moderate average increases in math and literacy standardized scores among pupils in treatment communities and to larger achievement gains for girls and disadvantaged children and regions. Improvements in child schooling, cognition, and nutrition constituted suggestive impact mechanisms, especially for educationally disadvantaged groups. The program combined equitable human capital accumulation with social protection, contributing to the "learning for all" sustainable development agenda.

AbstractThe current challenge of education systems is learning. Across low-income countries (LICs) and lower-middle-income countries (LMCs), 62 % of 10-year-olds could not read at a minimally sufficient level in 2015. This study provides an overview of recent spending on education and its correlation with learning outcomes. We show that the relationship between education spending and learning is historically weak. From 2000 to 2015, LICs and LMCs increased spending on education in primary schools by ~$137 per student, an 80 % inflation-adjusted increase, with no corresponding change on the average learning outcomes. We then conduct a benefit-cost analysis of candidate interventions that could increase learning at low cost. Two interventions – structured pedagogy and, teaching at the right level, with and without a technology component generate large benefit-cost ratios. If deployed uniformly to reach 90 % of the 467 million students in LICs and LMCs, these interventions would cost on average $18 per student per year or $7.6 billion annually, generating $65 in benefits for every $1 spent. The economic logic behind this finding is that the hard and costly work of getting children into primary schools has mostly been accomplished, leaving open the possibility of learning interventions that improve the efficiency of the existing education system at low cost. Our results show that increasing education expenditure by just 6 % could increase learning by 120 % if directed toward these highly cost-effective interventions.

Purpose: With aging, there is a decline in the ability to balance, leading to a predisposition to falls. The study’s aim was to verify the influence of pre-sarcopenia/sarcopenia on the ability to recover postural stability during balance perturbation. Methods: Fourteen older adults with pre-sarcopenia/sarcopenia (70.21 ± 2.80 years) and fourteen without sarcopenia (68.85 ± 3.50 years) were included. Sarcopenia was identified according to the European Consensus on Definition and Diagnosis (EWGSOP) criteria. Ten balance perturbations were applied. Variables Analyzed: Latency for the peak of center of pressure (CoP), CoP velocity, latency time and electromyographic (EMG) amplitude. Results: There was a difference between groups in the latency for the peak of CoP (p= 0.041), velocity of CoP (p= 0.016) and EMG amplitude of the lateral gastrocnemius (p= 0.019). There was difference in perturbations within pre-sarcopenic/sarcopenic group on latency for the peak of CoP in perturbations 1 and 2 (p= 0.023) and 1 and 10 (p= 0.041). There was a significant difference on velocity of CoP in non-sarcopenic group in comparison 1 and 2 (p= 0.040) perturbations. Conclusion: Older adults with pre-sarcopenia/sarcopenia require greater ankle plantarflexor activation to remain standing in response to perturbation compared to older adults without sarcopenia. In repetitive perturbations, the adaptations of pre-sarcopenic/sarcopenic group increase the magnitude of the EMG signal.

Extensive burn surgeries lead to a considerable amount of blood loss. Predicting preoperative blood loss is essential for blood ordering and cross-matching. Accurate amount of ordered blood units ensures patients’ safety and minimizes cost. However, blood loss estimation is complicated due to a variety of factors influencing blood loss, including patient and operative-related variables. Currently, no standard method to predict blood loss exists prior to surgery. Our goal is to review factors influencing blood loss and formulas that can predict blood loss. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE databases for studies investigating blood loss in burn surgeries with a clear quantitative outcome. Fifteen studies were included, comprising 1613 subjects. All studies calculated blood loss and assessed possible related factors, and four studies proposed preoperative blood loss prediction formulas. Larger areas of tissue excised and grafted, younger age, and delayed surgery were correlated with increased blood loss. Varying decrease in blood loss was observed with tumescent usage and other bleeding control methods. Other variables produced inconsistent results. From four prediction formulas, only one formula, Dye’s Formula, had been applied and proven effective in reducing unused blood units clinically by up to 40% of cross-matched blood. Various confounding factors and dissimilarities between studies make reliable prediction method construction challenging. With consideration of diverse patient characteristics, some study develops formulas to achieve optimal patient care and avoid unnecessary hospital expenditure. Further research with consistent variables should be done to construct a standardized blood loss estimation formula.

Well-characterized small molecules are essential tools for studying the biology and therapeutic relevance of a target protein. However, many compounds reported in the literature and routinely studied in biomedical research lack the potency and selectivity required for mechanistic cellular studies on the function of a given protein. Furthermore, commercially available compounds often do not include useful tools developed by industry as part of their research and development efforts, as they frequently remain proprietary. The freely available donated chemical probe (DCP) library, fueled by generous donations of compounds from industry and academia, enables easy access to a steadily growing collection of these valuable and well-characterized tools. Here, we provide a systematic description of the current DCP library collection and their associated comprehensive characterization data, including a variety of in vitroand cellular assays. Of note, we characterized the set in relevant human primary models by employing hepatotoxicity screening in primary human liver spheroids and viability screening in patient-derived colorectal cancer organoids and matched normal-adjacent epithelium. Taken together, the DCP library represents a well-annotated, openly available collection of tool compounds for studying a wide range of targets, including kinases, G-protein-coupled receptors, and ion channels. As such, it represents a unique resource for the biomedical research community.

Food insecurity is a pressing global challenge with far-reaching consequences for health and well-being. However, little attention has focused specifically on the experiences of children and adolescents over the age of 5 y in food insecure households.

The number of successful drug development projects has been stagnant for decades despite major breakthroughs in chemistry, molecular biology, and genetics. Unreliable target identification and poor translatability of preclinical models have been identified as major causes of failure. To improve predictions of clinical efficacy and safety, interest has shifted to three-dimensional culture methods in which human cells can retain many physiologically and functionally relevant phenotypes for extended periods of time. Here, we review the state of the art of available organotypic culture techniques and critically review emerging models of human tissues with key importance for pharmacokinetics, pharmacodynamics, and toxicity. In addition, developments in bioprinting and microfluidic multiorgan cultures to emulate systemic drug disposition are summarized. We close by highlighting important trends regarding the fabrication of organotypic culture platforms and the choice of platform material to limit drug absorption and polymer leaching while supporting the phenotypic maintenance of cultured cells and allowing for scalable device fabrication. We conclude that organotypic and microphysiological human tissue models constitute promising systems to promote drug discovery and development by facilitating drug target identification and improving the preclinical evaluation of drug toxicity and pharmacokinetics. There is, however, a critical need for further validation, benchmarking, and consolidation efforts ideally conducted in intersectoral multicenter settings to accelerate acceptance of these novel models as reliable tools for translational pharmacology and toxicology.Significance StatementOrganotypic and microphysiological culture of human cells has emerged as a promising tool for preclinical drug discovery and development that might be able to narrow the translation gap. This review discusses recent technological and methodological advancements and the use of these systems for hit discovery and the evaluation of toxicity, clearance, and absorption of lead compounds.

Whiteflies (Hemiptera: Aleyrodidae) comprise a group of phytophagous insects, with worldwide distribution. This group has 1,556 described species, with members concentrated in the tropics. In Brazil, as the literature on species of Aleyrodidae and associated plants is limited, our study presents species of whiteflies and their host plants collected in some Brazilian regions. New host plants or new occurrence locations for species already known in the country are presented, in addition to the record of Aleurotulus laneus Martin, a species not yet reported in Brazil. [ABSTRACT FROM AUTHOR]

Organotypic and microphysiological systems (MPS) that can emulate the molecular phenotype and function of human tissues, such as liver, are increasingly used in preclinical drug development. However, despite their improved predictivity, drug development success rates have remained low with most compounds failing in clinical phases despite promising preclinical data. Here, it is tested whether absorption of small molecules to polymers commonly used for MPS fabrication can impact preclinical pharmacological and toxicological assessments and contribute to the high clinical failure rates. To this end, identical devices are fabricated from eight different MPS polymers and absorption of prototypic compounds with different physicochemical properties are analyzed. It is found that overall absorption is primarily driven by compound hydrophobicity and the number of rotatable bonds. However, absorption can differ by >1000‐fold between polymers with polydimethyl siloxane (PDMS) being most absorptive, whereas polytetrafluoroethylene (PTFE) and thiol‐ene epoxy (TEE) absorbed the least. Strikingly, organotypic primary human liver cultures successfully flagged hydrophobic hepatotoxins in lowly absorbing TEE devices at therapeutically relevant concentrations, whereas isogenic cultures in PDMS devices are resistant, resulting in false negative safety signals. Combined, these results can guide the selection of MPS materials and facilitate the development of preclinical assays with improved translatability. Identical microdevices are fabricated from eight different polymers and it is found that absorption of prototypic compounds with different physicochemical properties differs by >1000‐fold between materials. Using 3D human liver cultures, it is shown that minimizing absorption can improve the accuracy of pharmacological or toxicological testing. These results have important implications for improving preclinical assay accuracy in drug development.

A 39 yo Caucasian woman, former smoker, with a previous history of gestational hypertension requiring therapy for several months, presented to the ED with persistent oppressive chest pain. No prior ischemic, constitutional or inflammatory symptoms emerged. Physical examination revealed a left carotid bruit and a continuous murmur at the base, Killip I. The ECG showed negative T waves in the inferior leads, the echo “point of care” normal systolic function, akinesia of the inferior wall, moderate aortic insufficiency, normal dimensions of the ascending aorta. HS T troponin rose to 188 ng/L and NT–proBNP 1621 pg/mL, CPR was normal. Coronary angiography revealed a tight subocclusive stenosis of the proximal right coronary artery trated by angioplasty with drug–eluting stent placement. In the ICU diminished pedal pulses were noticed, along with a significant discrepancy in blood pressure values between the four limbs (right upper 150/60 mmHg, left 140/60 mmHg, lower right 70/40 mmHg, left 60/40 mmHg). The echocardiogram showed normalized LV kinesis, moderate aortic insufficiency, normal dimensions of the ascending aorta and arch, flow acceleration at the isthmus (Vmax 4.6 m/s, Gmax 86 mmHg). CT angiography revealed thickening of the walls of the epiaortic vessels (with a non critical stenosis of the left carotid), of the thoracic and the abdominal aorta with complete occlusion of the subrenal segment and the inferior mesenteric artery (reconstituted by the Riolano artery and distal rectal arteries); the distal iliac arteries at the carrefour were separately reconstituted. 18F–FDG PET/CT confirmed diffuse hypercaptation along the ascending aorta, isthmus and proximal descending portion indicative of active vasculitis. Elevation of ESR 110 mm/h and CRP 21 mg/L was observed. The diagnosis of Takayasu‘s arteritis (TA) was estabilished and treatment with prednisone and methotrexate was started, resulting in the normalization of acute phase markers and clinical stability at 3 months. TA is a vasculitis that primarily involves the aorta and its main branches. The diagnosis can be challenging due to the heterogeneous clinical course and lack of specific laboratory markers. Diagnostic delay and persisting inflammation can lead to catastrophic consequences. Despite its rarity, TA can account for a notable proportion of young women with documented myocardial ischemia; hence, cardiologists must be sensitive to this pathology particularly in high–risk populations.

PURPOSEThe purpose of this study was to examine the how different aspects of the birthing environment were associated with a parturient's states of consciousness, spirituality, and satisfaction with the childbirth experience.DESIGNThe study utilized a convergent mixed methods research design involving both quantitative and qualitative components with convenience sampling. In total, 276 Brazilian postpartum women completed a states of consciousness mini-test and the Expressions of Spirituality Inventory—Revised. A small subsample of women who gave birth in different settings were also interviewed. Quantitative data were examined using descriptive statistics, bivariate correlations, and analysis of variance and covariance. Qualitative interview data were thematically analyzed.MAJOR FINDINGSHome birth and the absence of a physician were associated with a higher occurrence of favorable non-ordinary states and satisfaction with childbirth. Spiritually-inclusive birth preparation was found to be associated with most spirituality and states of consciousness variables and more than childbirth satisfaction.MAIN CONCLUSIONNon-ordinary states emerged from a parturient's sense of security with their surroundings and from preparation for childbirth. Spiritual experiences were related to pre-existing spiritual beliefs and practices.

The realisation of human potential for development requires age-specific investment throughout the 8000 days of childhood and adolescence. Focus on the first 1000 days is an essential but insufficient investment. Intervention is also required in three later phases: the middle childhood growth and consolidation phase (5–9 years), when infection and malnutrition constrain growth, and mortality is higher than previously recognised; the adolescent growth spurt (10–14 years), when substantial changes place commensurate demands on good diet and health; and the adolescent phase of growth and consolidation (15–19 years), when new responses are needed to support brain maturation, intense social engagement, and emotional control. Two cost-efficient packages, one delivered through schools and one focusing on later adolescence, would provide phase-specific support across the life cycle, securing the gains of investment in the first 1000 days, enabling substantial catch-up from early growth failure, and leveraging improved learning from concomitant education investments.

A 55–years–old patient presents to emergency room with extensive anterior STEMI, complicated by acute pulmonary edema. The ECG showed sinusal tachycardia, Q waves in V1–V3, ST elevation >2mm V2–V6. The echocardiogram showed akinesia of the apex and anterolateral wall with severe reduction of contractile function (LVEF 30%). The patient was treated with CPAP, dual antiplatelet therapy and diuretics; the urgent coronary angiography showed three–vessel disease with occlusion of the proximal LAD, treated with PCI and two drug–eluting stents implantation. 48 after admission to ICU, the patient developed "combined" shock (IC↓ RVS↓ WP↑), sustained by both severe cardiac dysfunction and a septic complication, requiring inotropes and targeted antibiotic therapy (noradrenaline 0.02 gamma/Kg/min and piperacillin/tazobactam i.v). At 96 hours there was a recovery of contractile function and haemodynamics (CI from 1.8 to 2.7). Weaned from inotropes, he began therapy with low doses of ACE inhibitor, beta blocker, antialdosteronic. On the 7th day of hospitalization, without ischemic and/or electrolyte "triggers", the patient developed "arrhythmic storm" with incessant sustained ventricular tachycardias. Arrhythmias persisted despite antiarrhythmics (magnesium sulfate, amiodarone, lidocaine), IOT, sedation, mechanical ventilation. The temporary pacemaker for overdrive pacing was placed in. After placement of IABP, the patient underwent revascularization of residual coronary artery stenosis. Despite 1 hour of assistance (ABLS), incessant ventricular tachycardia persisted; a third–level center for VA–ECMO inside support was called. After positioning VA–ECMO there was progressive clinical stabilization and –concomitantly– a progressive reduction of ventricular tachycardias. ECMO support was needed for over 7 days due to persistence of arrhythmic storm; it was slowly weaned with stabilization of the patient; an AICD was implanted. Residual function of the left ventricle was mild reduced (LVEF40%) despite protracted CPR. There wasn’t residual cognitive impairment. Implementation of multidisciplinary teams in the spoke centers would improve protocols and early treatments in patients with cardiogenic shock; spoke centers would provide early access to life–saving therapies and safe transfer to hub centers.

Food environments can play important roles in shaping nutrition and health outcomes. One such environment that has potential to affect youth is the school food environment. In contrast to higher-income countries, however, there is a critical evidence gap on the role of school food environments on children and adolescents in low- and middle-income countries. This mixed-methods study contributes to filling this gap by investigating the role of school food environments on dietary behaviours of children and adolescents in Ghana. It draws on data from household and school questionnaires as well as focus group discussions collected as part of the baseline for an impact evaluation of the Ghana School Feeding Programme (GSFP). Multi-level regression models were fitted with random intercepts at the individual, household and community levels. Excerpts from the focus group discussions provided a deeper understanding of quantitative findings. Children and adolescents who received free school meals provided by the GSFP or who lived further away from school were less likely to go home for lunch. More than half of sampled schools reported offering foods for sale by independent vendors, the most common being meals followed by confectionery, fruit and sugar-sweetened beverages. Predictors of bringing money to school to buy food included non-receipt of free school meals, adolescence, greater commuting distance from home, household asset score, and urban location. Policy efforts focusing on the school food environment may contribute to healthy dietary behaviours for children and adolescents with positive impacts over the lifecourse.

•In the cinerite samples there are impressions of sacred/medicinal plants.•Mandrake plants, recorded in the samples, are currently absent in Campania.•Mandrake impressions helps to define the seasonal interval of the Pollena eruption.

Background: Interventions that enhance linkages between healthy diets and local agriculture can promote sustainable food systems. Home-grown school feeding programs present a promising entry point for such interventions, through the delivery of nutritious menus and meals.Objective: To describe the adaptation of the School Meals Planner Package to the programmatic and environmental reality in Ghana during the 2014 to 2015 school year.Methods: Guided by a conceptual framework highlighting key considerations and trade-offs in menu design, an open-source software was developed that could be easily understood by program implementers. Readily available containers from markets were calibrated into “handy measures” to support the provision of adequate quantities of food indicated by menus. Schools and communities were sensitized to the benefits of locally sourced, nutrient-rich diets. A behavior change communication campaign including posters and songs promoting healthy diets was designed and disseminated in schools and communities.Results: The School Meals Planner Package was introduced in 42 districts in Ghana, reaching more than 320 000 children. Monitoring reports and feedback on its use were positive, demonstrating how the tool can be used by planners and implementers alike to deliver nutritious, locally-sourced meals to schoolchildren. The value of the tool has been recognized at the highest levels by Ghana’s government who have adopted it as official policy.Conclusions: The School Meals Planner Package supported the design of nutritious, locally sourced menus for the school feeding program in Ghana. The tool can be similarly adapted for other countries to meet context-specific needs.

The objective of this study was to quantify tissue interface pressures that occurred in the sacrum, shoulder, and buttockthigh regions while using (1) pillows or (2) a wedge system for off-loading of sacral pressures.

Medium-energy ion spectroscopy (MEIS), scanning transmission electron microscopy (STEM) and X-ray photoemission spectroscopy (XPS) were used to investigate the composition and microstructure of LaAlO3/SrTiO3(LAO/STO) interfaces grown by pulsed laser deposition of LAO on TiO2-terminated STO substrates under different oxidizing conditions. MEIS and XPS indicated Sr/La and Al/Ti intermixing within several atomic layers at all studied interfaces. XPS and STEM revealed that La diffuses deeper than Al. Analysis of the MEIS data suggests inhomogeneous lateral distribution of the diffused elements. This is further supported by the observation of a large positive magneto-resistance at low temperatures. We discuss the role of lateral inhomogeneities on the formation of the electron gas at the LAO/STO interface.

This review is an up-to-date analysis of the genetic diagnosis and therapeutic strategies for limb girdle muscular dystrophies (LGMDs).

Duchenne and Becker muscular dystrophies are caused by a large number of different mutations in the dystrophin gene. Outside of the deletion/duplication “hot spots,” small mutations occur at unpredictable positions. These account for about 15 to 20% of cases, with the major group being premature stop codons. When the affected male is deceased, carrier testing for family members and prenatal diagnosis become difficult and expensive. We tailored a cost-effective and reliable strategy to discover point mutations from stored DNA samples in the absence of a muscle biopsy. Samples were amplified in combinatorial pools and tested by denaturing high-performance liquid chromatography analysis. An anomalous elution profile belonging to two different pools univocally addressed the allelic variation to an unambiguous sample. Mutations were then detected by sequencing. We identified 121 mutations of 99 different types. Fifty-six patients show stop codons that represent the 46.3% of all cases. Three non-obvious single amino acid mutations were considered as causative. Our data support combinatorial denaturing high-performance liquid chromatography analysis as a clear-cut strategy for time and cost-effective identification of small mutations when only DNA is available.

The frequency of various limb-girdle muscular dystrophy (LGMD) molecular diagnoses has previously been investigated only in cohorts of patients presenting LGMD phenotype.

Mutations in the human alpha-sarcoglycan gene on chromosome 17q21.2 have been shown to cause a severe childhood autosomal recessive muscular dystrophy, a less severe limb girdle muscular dystrophy, exercise intolerance, or asymptomatic hyperCKemia. Here, we describe the clinical findings in a German family harboring a 371 T > C (Ile124Thr) missense mutation in the alpha-sarcoglycan gene. Whereas our index patient, an 11-year-old girl homozygous for this mutation, presented with a severe Duchenne-like phenotype, 7 out of 12 heterozygous mutation carriers from three generations showed mild to moderate scapular winging. In analogy to symptomatic female dystrophinopathy carriers, our results suggest that heterozygous alpha-sarcoglycan gene mutation carriers can be symptomatic with selective muscle weakness. This finding may be attributed to an additional negative variation in a yet unknown modifier gene essential to the function of the sarcoglycan complex in shoulder girdle muscles.

Mutations in the human alpha‐sarcoglycan gene on chromosome 17q21.2 have been shown to cause a severe childhood autosomal recessive muscular dystrophy, a less severe limb girdle muscular dystrophy, exercise intolerance, or asymptomatic hyperCKemia. Here, we describe the clinical findings in a German family harboring a 371 T > C (Ile124Thr) missense mutation in the alpha‐sarcoglycan gene. Whereas our index patient, an 11‐year‐old girl homozygous for this mutation, presented with a severe Duchenne‐like phenotype, 7 out of 12 heterozygous mutation carriers from three generations showed mild to moderate scapular winging. In analogy to symptomatic female dystrophinopathy carriers, our results suggest that heterozygous alpha‐sarcoglycan gene mutation carriers can be symptomatic with selective muscle weakness. This finding may be attributed to an additional negative variation in a yet unknown modifier gene essential to the function of the sarcoglycan complex in shoulder girdle muscles.

Fusarium oxysporumf.sp. lilii(Fol), the causal agent of lily basal rot, produced fusaric acid (FA) in aseptic culture. This toxin induced phytotoxicity symptoms on in vitro-grown lily bulblets of two different cultivars: the Fol-susceptible cultivar was more sensitive to the toxin than the Fol-resistant cultivar. When cultured in the presence of FA, the Fol-susceptible cultivar showed a greater tendency to accumulate FA within its tissues than the Fol-resistant cultivar. The polyphenol oxidase activity of the bulblets was inhibited by 1 mmol L−1FA in both the cultivars, while at lower FA concentrations the enzyme activity increased only in the Fol-susceptible cultivar. Peroxidase showed a steady activity at the 1 mmol L−1FA concentration in both the cultivars, while at lower FA dosages its activity increased. Within the Fol-infected in vivotissues of both the lily cultivars, FA was detectable only in traces. The role of this toxin in the lily basal rot disease seems therefore to be of marginal importance.

Summary.: Proton Nuclear Magnetic Resonance (NMR) Spectroscopy of urine (as well as of other biological fluids) is a very powerful technique enabling multi-component analysis useful in both diagnosis and follow-up of a wide range of inherited metabolic diseases. Among these pathologies, cystinuria is characterised by accumulation in urine of four dibasic amino acids, namely lysine, arginine, ornithine and cystine; the last one, being only slightly water soluble, generates urolithiasis. The mentioned aminoacids can be detected in the urine NMR spectrum of cystinuric patients, the most abundant being the lysine (5 mM and over are often detected), whose typical signals become very high; arginine and ornithine are also usually detectable, although pathologic concentrations are lower (usually below 2 mM). The proposed NMR technique is also suitable in monitoring the therapy with α-mercaptopropionylglycine (MPG), providing quantitation of several metabolites of interest in the follow-up of the pathology, like cystine, creatinine and citrate.

The synthesis of some crosslinked polymers based on a segmented-chain polymeric mesogen containing variable amounts of a side chain substituent is reported. The unswollen networks show thermotropic mesomorphism of nematic character whose stability decreases with increasing substitution and crosslink density. Depending on the same parameters, the swollen networks may show optical anisotropy at room temperature whose origin is attributed to phase separation

Delays that occur on a construction projects can cause project performance inefficiencies and can even add to the project cost. Factors due to project delays consist of many things that can cause project delays. This study aims to find a top ten similarity factor that causes delays in a construction projects based on the results of research in Jakarta construction projects against previous studies in other countries. From a total of 100 distributed questionnaires, 88 (88%) were filled in correctly and returned as data analysis material. The Data from the survey results were analyzed using Statistical Software Package (SPSS) to produce a ranking for Project Delay Factor. The ranking of the study was then re-analyzed based on the similarity of the previous research so that the similar Project Delay Factor Ranking was obtained.

The aim of this study was to investigate the effects of aquatic exercise on mental health, functional autonomy and oxidative stress parameters in depressed elderly individuals.

Impaired switching from fetal hemoglobin (HbF) to adult globin gene expression leads to hereditary persistence of fetal hemoglobin (HPFH) in adult life. This is of prime interest because elevated HbF levels ameliorate beta-thalassemia and sickle cell anemia. Fetal hemoglobin levels are regulated by complex mechanisms involving factors linked or not to the beta-globin gene locus. Recently, we reported an inverse relationship between Ggamma-globin gene (HBG2) and Cold Shock Domain Protein A (CSDA) expression levels. Based on mRNA differential display analysis, RNA interference and over-expression studies in K562 and primary erythroid cells we postulated that CSDA could contribute to regulate HBG2 expression. The putative mechanism by which CSDA modulates HBG2 expression was investigated in K562 cells by gene reporter assays on wild-type and mutant constructs of the HBG2 promoter region suspected to bind CSDA, providing experimental evidence that CSDA acts as repressor of HBG2 expression. Furthermore, chromatin immunoprecipitation (ChIP) analysis on K562 cells showed that CSDA interacts in vivo with this promoter region. In this way we were able to demonstrate that CSDA modulates HBG2 expression at least in part at the transcriptional level (Petruzzelli R et al, Br J Haematol 2010). The CSDA gene is located at position 12p13.1 and comprises 10 exons. The C-terminus (exons 6–9) is involved in protein-protein interactions. Alternative splicing of exon 6 results in two main isoforms, namely CSDA isoform a and isoform b, which show different C-terminal domains, potentially able to take part to specific protein complexes. We found that expression levels of CSDA isoform a were reduced in HPFH patients respect to isoform b. These findings suggested that isoform a could be much more involved in repression of HBG2 expression compared to isoform b. To identify putative CSDA interactors, we over-expressed these two FLAG-tagged CSDA isoforms in K562 cells. Western-blot analysis on proteins immunoprecipitated with a FLAG antibody revealed the presence of NF-kB p50 and p65 subunits and histone deacethylase 2 (HDAC2) only in samples co-immunoprecipitated with CSDA isoform a, but not with isoform b (Fig. 1). By ChIP assays with antibodies against p65, p50 and HDAC2, we demonstrated that both the NF-kB p50-p65 heterodimer and HDAC2 interact with the –200 bp region of the HBG2 promoter containing the CSDA binding site (Fig. 2). To examine the role of NF-kB and histone deacetylases on the transcriptional repression of HBG2 expression, we treated K562 cells with the proteasome inhibitor bortezomib which blocks the nuclear traslocation and transcriptional activity of the NF-kB p65-p50 complex or with the histone deacetylase inhibitor trichostatin A (TSA). Quantitative analysis by Real Time PCR showed that HBG2 expression increased following either bortezomib or TSA treatments. Furthermore, by ChIP analysis we were able to demonstrate that knock-down of CSDA abolished these interactions. To investigate if treatment with bortezomib or TSA affects the histone acetylation levels at the -200 bp region of the HBG2 promoter, we performed ChIP assays in K562 cells using an anti-acetyl-H3 antibody. Results indicated that both these drugs induces a considerable increase in H3 acetylation levels at the -200 bp region of the HBG2 promoter (Fig. 3). Taken altogether these data indicate that NF-kB and HDAC2 interact with CSDA to form a multiprotein complex which take part to the regulation of HBG2 expression by modulating local chromatin conformation. Furthermore, our study contributes to better define the role played by CSDA in fetal globin gene expression and shed novel light on the molecular mechanisms involved in globin gene switching.No relevant conflicts of interest to declare.