Preschool Children's Loose Parts Play and the Relationship to Cognitive Development: A Review of the Literature.
Play is an integrative process, and the skills acquired in it-overcoming impulses, behavior control, exploration and discovery, problem-solving, reasoning, drawing conclusions, and attention to processes and outcomes are foundational cognitive structures that drive learning and motivation. Loose parts play is a prominent form of play that many scholars and educators explicitly endorse for cognitive development (e.g., divergent thinking, problem-solving). It is unique among play types because children can combine different play types and natural or manufactured materials in one occurrence. While educators and policymakers promote the benefits of loose parts play, no previous research has explored the direct relationship between preschool-age children's indoor loose parts play experiences and cognitive development. We address this gap by bringing together the relevant literature and synthesizing the empirical studies on common play types with loose parts, namely object and exploratory, symbolic and pretend, and constructive play. We also focus on studies that examine children's experiences through loose parts, highlighting the impact of different play types on learning through the reinforcement of cognitive skills, such as executive function, cognitive self-regulation, reasoning, and problem-solving. By examining the existing literature and synthesizing empirical evidence, we aim to deepen our understanding of the relationship between children's play with loose parts and its impact on cognitive development. Ultimately, pointing out the gaps in the literature that would add to the body of knowledge surrounding the benefits of play for cognitive development and inform educators, policymakers, and researchers about the significance of incorporating loose parts play into early childhood education.


Effects of aging and antihypertensive treatment on aortic internal diameter in spontaneously hypertensive rats.
The effect of antihypertensive treatment on the development of large-artery remodeling in young animals has been widely studied, but reversal of established changes in older hypertensive animals has been largely ignored, although the latter represents a better paradigm for the human condition. We studied the effect of treatment with captopril plus hydrochlorothiazide, from 3 months onward, on geometry and wall stress of the thoracic aorta of adult (9 months, maturation) and old (15 months, senescence) spontaneously hypertensive rats; normotensive Wistar-Kyoto rats were used as controls. At 3 months of age, blood pressure, medial cross-sectional area, and internal diameter were higher in spontaneously hypertensive rats than in Wistar-Kyoto rats. In both strains, medial cross-sectional area and lumen diameter increased during maturation; there was little change with senescence. Changes in blood pressure were minor. Because medial hypertrophy failed to compensate for the wider lumen and higher intraluminal pressure in spontaneously hypertensive rats, medial stress was higher in these rats than in Wistar-Kyoto rats. Captopril plus hydrochlorothiazide rapidly lowered blood pressure and medial cross-sectional area. Despite a marked fall in blood pressure, the internal diameter of the thoracic aorta of treated animals was similar to that of untreated animals after 6 months of treatment and started to fall only after the animals had been treated for 1 year. Thus, under treatment with captopril plus hydrochlorothiazide, medial stress remained elevated, even after very-long-term treatment, because medial cross-sectional area was not adapted to internal diameter. We suggest that some changes in large-artery structure associated with hypertension and aging, such as the increase in diameter, take considerable time to regress after blood pressure is lowered, and this may explain why, despite treatment, wall stress remains elevated.


Functions and imaging of mast cell and neural axis of the gut.
Close association between nerves and mast cells in the gut wall provides the microanatomic basis for functional interactions between these elements, supporting the hypothesis that a mast cell-nerve axis influences gut functions in health and disease. Advanced morphology and imaging techniques are now available to assess structural and functional relationships of the mast cell-nerve axis in human gut tissues. Morphologic techniques including co-labeling of mast cells and nerves serve to evaluate changes in their densities and anatomic proximity. Calcium (Ca(++)) and potentiometric dye imaging provide novel insights into functions such as mast cell-nerve signaling in the human gut tissues. Such imaging promises to reveal new ionic or molecular targets to normalize nerve sensitization induced by mast cell hyperactivity or mast cell sensitization by neurogenic inflammatory pathways. These targets include proteinase-activated receptor (PAR) 1 or histamine receptors. In patients, optical imaging in the gut in vivo has the potential to identify neural structures and inflammation in vivo. The latter has some risks and potential of sampling error with a single biopsy. Techniques that image nerve fibers in the retina without the need for contrast agents (optical coherence tomography and full-field optical coherence microscopy) may be applied to study submucous neural plexus. Moreover, the combination of submucosal dissection, use of a fluorescent marker, and endoscopic confocal microscopy provides detailed imaging of myenteric neurons and smooth muscle cells in the muscularis propria. Studies of motility and functional gastrointestinal disorders would be feasible without the need for full-thickness biopsy.


Preliminary experience with a method of quadricepsplasty in recurrent subluxation of the patella.
Nineteen knees were treated for recurrent subluxation or dislocation of the patella by lateral and distal transfer of the vastus medialis with or without release of the lateral retinaculum. Fifty-eight per cent has good or excellent and 42 per cent had poor results after a mean follow-up of twenty-nine months. The factors that predisposed to failure were genu valgum greater than 15 degrees and, to a lesser extent, palpable synovitis associated with symptomatic chondromalacia patellae.


Health-related quality of life among adults living with diabetic foot ulcers: a meta-analysis.
To undertake a systematic review of the literature to investigate the HRQOL among adults living with DFUs. A systematic search of the medical and nursing/health content databases including MEDLINE, CINAHL, and PsycINFO was conducted up to November 2018. The methodological quality of each study was assessed independently by all authors using the Joanna Briggs Institute checklist. Data analysis was conducted using the Comprehensive Meta-analysis software. All analyses were performed using random-effects models and heterogeneity was quantified. A total of 12 studies were included in the review. Overall, the HRQOL of participants in the studies was poor on four of eight subscales in the SF-36: physical functioning (mean = 42.75, SE 1.5); role physical (mean = 20.61, SE 3.4); general health (mean = 39.52, SE 1.7); and vitality (mean = 45.73, SE 2.8). In addition, presence of pain, high levels of C-reactive protein (> 10 mg/L), ulcer size > 5 cm2, Ankle Brachial Index < 0.9, high glycosylated haemoglobin and body mass index > 25 kg/m2 were associated with poorer HRQOL in people with DFUs. This review has provided evidence indicating that people with DFUs have a significantly lower HRQOL. Evidence-based interventions to improve the HRQOL in this group of people is needed.


Decoding the expression pattern of MUC3A in gastric adenocarcinoma: unveiling the key to successful immunotherapy.
Despite the promise of immunotherapy for gastric adenocarcinoma, resistance is common, necessitating the validation of new targets. Based on our previous bioinformatics analysis, the MUC3A antigen emerged as a promising candidate for immunotherapy against gastric adenocarcinoma. However, a comprehensive understanding of its expression at protein level remains elusive, despite its crucial role in determining clinical response. We also sought to establish a connection between the expression pattern and relevant clinical variables of the disease, whenever feasible. Immunohistochemistry was used to determine the percentage of MUC3A-positive tumor cells in primary (PT) and metastatic tumor (MT) sites of 190 gastric adenocarcinoma patients. We also evaluated the association between MUC3A expression and variables such as Lauren classification, history of neoadjuvant chemotherapy and/or radiotherapy, and overall patient survival. Median MUC3A expression was 50% in PT and 70% in MT sites, exhibiting a positive correlation. MT intestinal type showed significantly higher MUC3A expression compared to other types. Neoadjuvant therapy history did not affect MUC3A expression. Higher MUC3A expression correlated with improved survival. Based on our previous bioinformatics data and the consistently high expression of MUC3A on gastric tumor cells, we propose advancing experimental aspects of anti-MUC3A immunotherapy for gastric adenocarcinoma.


Henoch-Schonlein purpura nephritis: pathophysiology, treatment, and future strategy.
Henoch-Schönlein purpura nephritis is a rare kidney disease leading to chronic kidney disease in a non-negligible percentage of patients. Although retrospective studies suggest beneficial effects of some therapies, prospective randomized clinical trials proving treatment efficacy are still lacking. The dilemma of spontaneous recovery even in patients with severe clinical and histologic presentation and of late evolution to chronic kidney disease in patients with mild initial symptoms renders it difficult for clinicians to expose patients to treatment protocols that are not evidence-based. A better understanding of the pathophysiology of progression to chronic kidney disease in Henoch-Schönlein purpura patients could be achieved by designing prospective international multicenter studies looking at determinants of clinical and histopathological evolution as well as possible circulating and urinary markers of progression. Such studies should be supported by a database available on the web and a new histologic classification of kidney lesions. This paper reports clinical, pathologic, and experimental data to be used for this strategy and to assist clinicians and clinical trial designers to reach therapeutic decisions.


Dispersion-enhanced phase noise effects on reduced-guard-interval CO-OFDM transmission.
Unlike conventional CO-OFDM systems, we show in this paper that reduced-guard-interval (RGI) CO-OFDM systems experience subcarrier-dependent phase noise (PN) from the local oscillator laser. This phenomenon manifests in RGI-CO-COFM systems because the chromatic dispersion (CD) induced walk-off becomes comparable to the OFDM symbol length. We term this phenomenon the dispersion enhanced PN (DEPN). In this work an analytical study of the impact of DEPN on CO-OFDM transmission is conducted. We develop a system-level analytical model and calculate the variance of the dispersion-induced subcarrier-dependent phase rotation term (PRT) using two different distribution patterns of pilot subcarriers (PS). Moreover, we present a bit error rate (BER) estimator to quantify the system performance degradation due to PRT. Numerical simulations are then performed to verify the analytical model. Finally, we propose a grouped maximum-likelihood (GML) phase estimation approach to mitigate the DEPN impairment, and demonstrate a 0.7-1.7 dB SNR improvement at BER=10⁻³ for typical 100 Gb/s RGI CO-OFDM systems.


Validation of a food quantification picture book targeting children of 0-10 years of age for pan-European and national dietary surveys.
The aim of the present study was to validate thirty-eight picture series of six pictures each developed within the PANCAKE (Pilot study for the Assessment of Nutrient intake and food Consumption Among Kids in Europe) project for portion size estimation of foods consumed by infants, toddlers and children for future pan-European and national dietary surveys. Identical validation sessions were conducted in three European countries. In each country, forty-five foods were evaluated; thirty-eight foods were the same as the depicted foods, and seven foods were different, but meant to be quantified by the use of one of the thirty-eight picture series. Each single picture within a picture series was evaluated six times by means of predefined portions. Therefore, thirty-six pre-weighed portions of each food were evaluated by convenience samples of parents having children aged from 3 months to 10 years. The percentages of participants choosing the correct picture, the picture adjacent to the correct picture or a distant picture were calculated, and the performance of individual pictures within the series was assessed. For twenty foods, the picture series performed acceptably (mean difference between the estimated portion number and the served portion number less than 0.4 (SD < 1.1)). In addition, twelve foods were rated acceptable after adjustment for density differences. Some other series became acceptable after analyses at the country level. In conclusion, all picture series were acceptable for inclusion in the PANCAKE picture book. However, the picture series of baby food, salads and cakes either can only be used for foods that are very similar to those depicted or need to be substituted by another quantification tool.


Older adults' experiences and perceptions of living with Bomy, an assistive dailycare robot: a qualitative study.
An aging global population and preference for aging-in-place pose the opportunity for home-based robots to assist older adults with their daily routines. However, there is limited research into the experiences of older adults using robots in their own homes. In this descriptive qualitative feasibility study, older self-supporting and community-dwelling adults with various age-related health needs used Bomy, a dailycare robot in their homes for up to one week. The study explored the usefulness of the robot and participants' perceptions and experiences of using it. Bomy reminded them of daily activities and delivered cognitive stimulation games. Semi-structured in-person interviews were conducted, and data were analyzed thematically. Findings revealed an acceptance toward robots and the value of assistive dailycare robots. Participants perceived Bomy as a companion and made suggestions for improvement, including resolving technical issues associated with long-term use. Future functions should be personalizable, to accommodate each user's health needs and could also include smoke detection and reading aloud functions. Dailycare robots show promising potential in elderly care, especially in providing reminders for medication, health and wellbeing. This study highlights the importance of co-design and testing robotics in the environments for which they have been developed. Widespread implementation of Bomy might be feasible in the future, with some further adjustments.


Application of automatic statistical post-processing method for analysis of ultrasonic and digital dermatoscopy images.
Ultrasonic and digital dermatoscopy diagnostic methods are used in order to estimate the changes of structure, as well as to non-invasively measure the changes of parameters of lesions of human tissue. These days, it is very actual to perform the quantitative analysis of medical data, which allows to achieve the reliable early-stage diagnosis of lesions and help to save more lives. The proposed automatic statistical post-processing method based on integration of ultrasonic and digital dermatoscopy measurements is intended to estimate the parameters of malignant tumours, measure spatial dimensions (e.g. thickness) and shape, and perform faster diagnostics by increasing the accuracy of tumours differentiation. It leads to optimization of time-consuming analysis procedures of medical images and could be used as a reliable decision support tool in the field of dermatology.


Mitophagy: An Emerging Target in Ocular Pathology.
Mitochondrial function is essential for the viability of aerobic eukaryotic cells, as mitochondria provide energy through the generation of adenosine triphosphate (ATP), regulate cellular metabolism, provide redox balancing, participate in immune signaling, and can initiate apoptosis. Mitochondria are dynamic organelles that participate in a cyclical and ongoing process of regeneration and autophagy (clearance), termed mitophagy specifically for mitochondrial (macro)autophagy. An imbalance in mitochondrial function toward mitochondrial dysfunction can be catastrophic for cells and has been characterized in several common ophthalmic diseases. In this article, we review mitochondrial homeostasis in detail, focusing on the balance of mitochondrial dynamics including the processes of fission and fusion, and provide a description of the mechanisms involved in mitophagy. Furthermore, this article reviews investigations of ocular diseases with impaired mitophagy, including Fuchs endothelial corneal dystrophy, primary open-angle glaucoma, diabetic retinopathy, and age-related macular degeneration, as well as several primary mitochondrial diseases with ocular phenotypes that display impaired mitophagy, including mitochondrial encephalopathy lactic acidosis stroke, Leber hereditary optic neuropathy, and chronic progressive external ophthalmoplegia. The results of various studies using cell culture, animal, and human tissue models are presented and reflect a growing awareness of mitophagy impairment as an important feature of ophthalmic disease pathology. As this review indicates, it is imperative that mitophagy be investigated as a targetable mechanism in developing therapies for ocular diseases characterized by oxidative stress and mitochondrial dysfunction.


Current issues in the presentation of asymptomatic primary hyperparathyroidism: proceedings of the Fourth International Workshop.
This report summarizes data on traditional and nontraditional manifestations of primary hyperparathyroidism (PHPT) that have been published since the last International Workshop on PHPT. This subgroup was constituted by the Steering Committee to address key questions related to the presentation of PHPT. Consensus was established at a closed meeting of the Expert Panel that followed. Data from the 5-year period between 2008 and 2013 were presented and discussed to determine whether they support changes in recommendations for surgery or nonsurgical follow-up. Questions were developed by the International Task Force on PHPT. A comprehensive literature search for relevant studies was undertaken. After extensive review and discussion, the subgroup came to agreement on what changes in the recommendations for surgery or nonsurgical follow-up of asymptomatic PHPT should be made to the Expert Panel. 1) There are limited new data available on the natural history of asymptomatic PHPT. Although recognition of normocalcemic PHPT (normal serum calcium with elevated PTH concentrations; no secondary cause for hyperparathyroidism) is increasing, data on the clinical presentation and natural history of this phenotype are limited. 2) Although there are geographic differences in the predominant phenotypes of PHPT (symptomatic, asymptomatic, normocalcemic), they do not justify geography-specific management guidelines. 3) Recent data using newer, higher resolution imaging and analytic methods have revealed that in asymptomatic PHPT, both trabecular bone and cortical bone are affected. 4) Clinically silent nephrolithiasis and nephrocalcinosis can be detected by renal imaging and should be listed as a new criterion for surgery. 5) Current data do not support a cardiovascular evaluation or surgery for the purpose of improving cardiovascular markers, anatomical or functional abnormalities. 6) Some patients with mild PHPT have neuropsychological complaints and cognitive abnormalities, and some of these patients may benefit from surgical intervention. However, it is not possible at this time to predict which patients with neuropsychological complaints or cognitive issues will improve after successful parathyroid surgery.


[Leprosy situation in the world in 2009].
The epidemiological situation of leprosy is reported by the health division of each country to WHO. The reported data is collected by WHO and is immediately run on the Weekly Epidemiological Record. On this latest edition, data from the beginning of 2009 was reported. In almost all of the highly endemic countries, control activities have been integrated within the general healthcare system. However, early case detection and prompt treatment with MDT remain the cornerstone of leprosy. In order to reduce the physical, mental and socioeconomic burded of leprosy, much remains to be done.


Metabolic regulation by C1q/TNF-related protein-13 (CTRP13): activation OF AMP-activated protein kinase and suppression of fatty acid-induced JNK signaling.
Members of the C1q/TNF family play important and diverse roles in the immune, endocrine, skeletal, vascular, and sensory systems. Here, we identify and characterize CTRP13, a new and extremely conserved member of the C1q/TNF family. CTRP13 is preferentially expressed by adipose tissue and the brain in mice and predominantly by adipose tissue in humans. Within mouse adipose tissue, CTRP13 is largely expressed by cells of the stromal vascular compartment. Due to sexually dimorphic expression patterns, female mice have higher transcript and circulating CTRP13 levels than males. CTRP13 transcript and circulating levels are elevated in obese male mice, suggesting a potential role in energy metabolism. The insulin-sensitizing drug rosiglitazone also increases the expression of CTRP13 in adipocytes, which correlates with the insulin-sensitizing action of CTRP13. In a heterologous expression system, CTRP13 is secreted as a disulfide-linked oligomeric protein. When co-expressed, CTRP13 forms heteromeric complexes with a closely related family member, CTRP10. This heteromeric association does not involve conserved N-terminal Cys residues. Functional studies using purified recombinant protein demonstrated that CTRP13 is an adipokine that promotes glucose uptake in adipocytes, myotubes, and hepatocytes via activation of the AMPK signaling pathway. CTRP13 also ameliorates lipid-induced insulin resistance in hepatocytes through suppression of the SAPK/JNK stress signaling that impairs the insulin signaling pathway. Further, CTRP13 reduces glucose output in hepatocytes by inhibiting the mRNA expression of gluconeogenic enzymes, glucose-6-phosphatase and the cytosolic form of phosphoenolpyruvate carboxykinase. These results provide the first functional characterization of CTRP13 and establish its importance in glucose homeostasis.


Effects of Estradiol at Different Levels on Rabbit Endometrial Repair After Curettage.
To evaluate the effects of estradiol on endometrial regeneration and stromal fibrosis after endometrial curettage. This is an experimental, prospective study. Combining ovariectomized rabbits and different doses of estrogen replacement, we divided 33 female rabbits into 4 groups: control, low estrogen, moderate estrogen, and high estrogen. Hematoxylin-eosin staining and Masson's trichrome staining were used to assess the regeneration of endometrial glands and the degree of stromal fibrosis. Before curettage, estradiol at high serum level could stimulate endometrial gland regeneration as assessed by the number of endometrial glands in paraffin sections stained with hematoxylin and eosin. However, after curettage, both high and low doses of estradiol impaired glandular regeneration while enhancing stro-ma fibrosis, which was calculated as the ratio of stromal fibrosis area to endometrial area in paraffin sections stained with Masson's trichrome, as compared with the control group. In addition, estradiol is favorable to endometrial repair at the physiological level. Estradiol compromises glandular regeneration and promotes stromal fibrosis at both low and high serum levels but is favorable to endometrial repair at the physiological level. This study may provide new insight for the role of estrogen therapy after hysteroscopic division of intrauterine adhesion.


Response selection in schizophrenia.
Schizophrenia patients tend to have longer and more variable latencies of response than healthy control subjects. However, the distributions of data from the two groups overlap to a large extent. Therefore, we investigated (1) whether the process of response selection in schizophrenia patients is like that of slow control subjects or has different properties, and (2) whether the intra-individual variability of schizophrenia patients is intrinsically greater than that of control subjects or reflects their longer mean latency. To answer these questions we tested schizophrenia patients and healthy control subjects in a choice reaction time (RT) task with 2-choice and 4-choice conditions. We analyzed how mean RT in the 2-choice condition predicted mean RT in the 4-choice condition and found that the relation was significantly different between the two groups. In contrast, the intra-individual variability of RT was related to mean RT in the same way for schizophrenia patients and control subjects. These results indicate that the response selection process of schizophrenia patients was not simply a slower version of the same process engaged by control subjects, but it was a selection process with different dynamic properties. In contrast, schizophrenia patients did not have a greater intrinsic variability than control subjects. Furthermore, we found that the difference Deltat between RT measured in the 4-choice condition and RT predicted for the control group in the same condition could be used to discriminate effectively patients and control subjects. However, there was no significant association between Deltat and clinical variables. These results suggest that Deltat could reflect a trait impairment of schizophrenia independent from symptom profile. Finally, we suggest that the impairment of the process of selection of the motor response in schizophrenia reflects the alteration of the time-dependent patterns of neural activity that result from anomalies in the connectivity of the brain areas engaged for the selection of the motor response.


[Effect of cold adaptation on the resting membrane potential of muscle fibers].
In experiments on rats the membrane potential of single muscle fibers in fast (m. gastrocnemius) and slow (m. soleus) muscles were measured in animals adapted to cold and in the control group. The dynamics of the membrane potential was studied also during the first 60 min after the sciatic nerve dissection. In cold adapted rats the membrane potential of slow muscle fibers was higher than in the control group, but in the fast muscle fibers there was no difference between the two groups of animals. The denervation of muscles resulted in a progressive increase in the membrane potential. This hyperpolarization seems to be the result of deprivation of the c. n. s. from the activating influence. The data suggest that cold adaptation affects mainly the slow muscle fibers.


Human hepatocellular carcinoma (HCC) cells require both alpha3beta1 integrin and matrix metalloproteinases activity for migration and invasion.
Hepatocellular carcinoma (HCC) is the most frequent malignant tumor of the liver; prognosis depends on the tendency to metastasize. Cancer cell invasion is regulated by proteolytic remodeling of extracellular matrix components and by integrin expression. We have shown that matrix metalloproteinase-2 (MMP-2) and membrane-type-1 matrix metalloproteinase (MT1-MMP) cleave Laminin-5 (Ln-5), stimulating cell migration. Here we report that all HCC cells express MT1-MMP, migrate on Ln-1 and Collagen IV, whereas only HCC cells that express alpha3beta1 integrin secrete detectable levels of gelatinases, migrate on Ln-5, and invade through a reconstituted basement membrane (BM). Migration on Ln-5 is blocked by BB-94, an MMP inhibitor, and by MIG1, a monoclonal antibody that hinders migration on MMP-2-cleaved Ln-5. Invasion through a reconstituted BM is also inhibited by BB-94. HCC alpha3beta1-negative cells migrate on Ln-1 and Collagen IV, but not on Ln-5, and do not invade through a reconstituted BM, although they express MT1-MMP. Anti-alpha3beta1 blocking antibodies inhibit gelatinase activation, cell motility, and cell invasion through MATRIGEL: In vivo, alpha3beta1 integrin and Ln-5 are expressed in HCC tissue but not in normal liver. In conclusion, our data suggest that both alpha3beta1 integrin and gelatinase activity are required for HCC migration and invasion.


Peptide deformylase: a new target in antibacterial, antimalarial and anticancer drug discovery.
Peptide deformylase (PDF) is a class of metalloenzyme responsible for catalyzing the removal of the N-formyl group from N-terminal methionine following translation. PDF inhibitors are moving into new phase of drug development. Initially, PDF was considered as an important target in antibacterial drug discovery; however genome database searches have revealed PDF-like sequences in parasites (P. falciparum) and human, widening the utility of this target in antimalarial and anticancer drug discovery along with antibacterial. Using structural and mechanistic information together with high throughput screening, several types of chemical classes of PDF inhibitors with improved efficacy and specificity have been identified. Various drugs like, GSK-1322322 (Phase II), BB-83698 (Phase I), and LBM-415 (Phase I) have entered into clinical developments. Developments in the field have prompted us to review the current aspects of PDFs, especially their structures, different classes of PDF inhibitors, and molecular modeling studies. In nut shell, this review enlightens PDF as a versatile target along with its inhibitors and future perspectives of different PDF inhibitors.


One-step synthesis of a highly homogeneous SBA-NHC hybrid material: en route to single-site NHC-metal heterogeneous catalysts with high loadings.
The one-step synthesis of a mesoporous silica of SBA type, functionalized with a 1-(2,6-diisopropylphenyl)-3-propyl-imidazolium (iPr2Ar-NHC-propyl) cation located in the pore channels, is described. This material was obtained by the direct hydrolysis and co-condensation of tetraethylorthosilicate (TEOS) and 1-(2,6-diisopropylphenyl)-3-[3-(triethoxysilyl)propyl]-imidazolium iodide in the presence of Pluronic P123 as a non-ionic structure-directing agent and aqueous HCl (37%) as an acid catalyst. Small-angle X-ray diffraction measurements, scanning and transmission electron microscopies, as well as dinitrogen sorption analyses revealed that the synthesized material is highly mesoporous with a 2D hexagonal arrangement of the porous network. (13)C and (29)Si CP-MAS NMR spectroscopy confirmed that the material contains intact iPr2Ar-NHC-propyl cations, which are covalently anchored via silicon atoms fused into the silica matrix. Moreover, comparison of the latter data with those of an analogous post-synthetic grafted SBA-NHC material allowed us to establish that, as expected, (i) it is most probably more homogeneous and (ii) it shows a more robust anchoring of the organic units. Finally, elemental mapping by energy dispersive X-ray spectroscopy in the scanning electron microscope demonstrated a very homogeneous distribution of the imidazolium units within the one-pot material, moreover with a high content. This study thus demonstrates that a relatively bulky and hydrophilic imidazolium unit can be directly co-condensed with TEOS in the presence of a structure-directing agent to provide in a single step a highly ordered and homogeneous mesoporous hybrid SBA-NHC material, possessing a significant number of cationic NHC sites.


The use of hydrodynamic vortex separators and screening systems to improve water quality.
The paper reviews the evolution of Hydrodynamic Vortex Separators (HDVS) in the context of application as high rate rotary flow separators for achieving water quality improvements to meet with regulatory requirements in Europe and North America. The types of HDVS and their application for the control of wet-weather discharges such as combined sewer overflows (CSOs), sanitary sewer overflows (SSOs) and stormwater are outlined and a number of myths surrounding their use, dispelled. Reference is made to outputs of peer reviewed comprehensive monitoring, evaluation and demonstration projects on pilot and full-scale installations to demonstrate the efficacy and extensive track record of these systems. Recent developments and innovations in HDVS technologies are discussed, focusing on their combined use as solids liquid separators, contact vessels for wastewater disinfection, the incorporation of self-cleansing screening devices for the control of aesthetic pollutants (e.g. floatables) and the use of computational modelling for optimisation.


Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation.
A 5-week-old male infant presented with severe bacterial infections and poor wound healing, suggesting a neutrophil defect. Neutrophils from this patient exhibited decreased chemotaxis, polarization, azurophilic granule secretion, and superoxide anion (O(2)(-)) production but had normal expression and up-regulation of CD11b. Rac2, which constitutes >96% of the Rac in neutrophils, is a member of the Rho family of GTPases that regulates the actin cytoskeleton and O(2)(-) production. Western blot analysis of lysates from patient neutrophils demonstrated decreased levels of Rac2 protein. Addition of recombinant Rac to extracts of the patient neutrophils reconstituted O(2)(-) production in an in vitro assay system. Molecular analysis identified a point mutation in one allele of the Rac2 gene resulting in the substitution of Asp57 by an Asn (Rac2(D57N)). Asp57 is invariant in all defined GTP-binding proteins. Rac2(D57N) binds GDP but not GTP and inhibits oxidase activation and O(2)(-) production in vitro. These data represent the description of an inhibitory mutation in a member of the Rho family of GTPases associated with a human immunodeficiency syndrome.


Apnoea-triggered increase in fraction of inspired oxygen in preterm infants: a randomised cross-over study.
To investigate the impact of a pre-emptive apnoea triggered oxygen response on oxygen saturation (SpO2) targeting following central apnoea in preterm infants. Interventional crossover study of a 12-hour period of automated oxygen control with an apnoea response (AR) module, nested within a crossover study of a 24-hour period of automated oxygen control compared with aggregated data from two flanking 12-hour periods of manual control. Neonatal intensive care unit PATIENTS: Preterm infants receiving non-invasive respiratory support and supplemental oxygen; median (IQR) birth gestation 27 (26-28) weeks, postnatal age 17 (12-23) days. Automated oxygen titration with an automated control algorithm modified to include an AR module. Alterations to inspired oxygen concentration (FiO2) were actuated by a motorised blender. Desired SpO2 range was 90-94%. Apnoea detection was by capsule pneumography. Duration, magnitude and area under the curve (AUC) of SpO2 deviations following apnoea; frequency and duration of apnoeic events. Comparisons between periods of manual, automated and automated control with AR module. In 60 studies in 35 infants, inclusion of the AR module significantly reduced AUC for SpO2 deviations below baseline compared with both automated and manual control (manual: 87.1%±107.6% s, automated: 84.6%±102.8% s, AR module: 79.4%±102.7% s). However, there was a coincident increase in SpO2 overshoot (AUC (SpO2>SpO2(onset)); manual: 44.3±99.9% s, automated: 54.7%±103.4% s, AR module: 65.7%±126.2% s). Automated control with a pre-emptive apnoea-triggered FiO2 boost resulted in a modest reduction in post-apnoea hypoxaemia, but was followed by a greater SpO2 overshoot. ACTRN12616000300471.


Transcriptional regulation of CDKN2A/p16 by sirtuin 7 in senescence.
Cell senescence is a state of limited cell proliferation during a stress response or as part of a programmed process. When a senescent cell stops dividing, maintaining metabolic activity contributes to cellular homeostasis maintenance. In this process, the cell cycle is arrested at the G0/G1 phase. p16INK4A protein is a key regulator of this process via its cyclin‑dependent kinase inhibitor (CDKI) function. CDKI 2A (CDKN2A)/p16 gene expression is regulated by DNA methylation and histone acetylation. Sirtuins (SIRTs) are nicotinamide dinucleotide (NAD+)‑dependent deacetylases that have properties which prevent diseases and reverse certain aspects of aging (such as immune, metabolic and cardiovascular diseases). By performing quantitative PCR, Western blot, ChIP, and siRNAs assays, in this study it was demonstrated that CDKN2A/p16 gene transcriptional activation and repression were accompanied by selective deposition and elimination of histone acetylation during the senescence of MRC5 cells. Specifically, significant H3K9Ac and H3K18Ac enrichment in cells with a senescent phenotype concomitant with CDKN2A/p16 gene overexpression was demonstrated compared with the non‑senescent phenotype. Furthermore, the presence of H3K18Ac in deacetyl‑transferase SIRT7 knockdown MRC5 cells allowed CDKN2A/p16 promoter activation. These results suggested that SIRT7 served as a critical component of an epigenetic mechanism involved in senescence mediated by the CDKN2A/p16 gene.


Giardia duodenalis infection among rural communities in Yemen: A community-based assessment of the prevalence and associated risk factors.
To investigate the prevalence and risk factors of Giardia infection among rural communities among rural communities in Yemen. In this cross-sectional study, a total of 605 stool samples were collected and screened for the presence of Giardia duodenalis (G. duodenalis) cysts and/or trophozoites by using three different diagnostic methods: direct smear, formalin-ether sedimentation, and trichrome staining. A pre-tested questionnaire was used to collect information on the demographic, socioeconomic, behavioural and environmental characteristics of the participants. Overall, 28.1% (170/605) of the participants were infected by G. duodenalis. The prevalence was significantly higher among male participants compared to female (P = 0.034); however, it was not significant among different age groups (P > 0.05). Univariate and multivariate analyses identified four variables as the significant key risk factors of Giardia infection among the sampled communities. These are, in addition to being of the male gender, using unsafe water sources for drinking water, not washing hands after defecation, presence of other family members infected with Giardia, and close contact with domestic animals. The study reveals that Giardia infection is still prevalent among rural communities in Yemen. The provision of clean and safe drinking water, proper sanitation, and health education regarding personal hygiene practices, particularly handwashing, as well as identifying and treating infected family members is imperative and these interventions should be considered in a strategy to control intestinal parasites among these communities in order to curtail the transmission and morbidity caused by G. duodenalis.


The Effects of Diclofenac Suppository and Intravenous Acetaminophen and their Combination on the Severity of Postoperative Pain in Patients Undergoing Spinal Anaesthesia During Cesarean Section.
The main tasks of postoperative care are postoperative pain and complications control which play an important role in accelerating the recovery of patient's general condition. This study was performed in order to compare the effects of diclofenac suppository, intravenous acetaminophen and their combination on the severity of postoperative pain in patients undergoing spinal anaesthesia for cesarean section in Sayyad Shirazi teaching Hospital, Gorgon, Iran. This was a double-blind clinical trial on 90 patients undergoing cesarean section. The patients were randomly divided into three groups, group A: 100 mg diclofenac suppository, group B: 1000 mg intravenous acetaminophen, group C: 100 mg diclofenac suppository and 500 mg intravenous acetaminophen. The same spinal anaesthesia circumstances were applied for all the participants. At the end of surgery, pain severity was assessed according to VAS scale at different times. Data were then analysed by SPSS 18 statistical software. The mean age of participants was (28.27±6.07). There was significant difference between the mean pain scores of the three groups before the intervention (p=0.018), which was considered as co-variate. This difference was more notable between the combination of acetaminophen - diclofenac group and diclofenac alone. After the intervention, significant difference was observed in mean pain severity between acetaminophen group and the combination group and also between diclofenac and the combination group. During the study, the least mean pain severity was found in the combination group and the highest was observed in the diclofenac group. Results of this study indicates a significant effect of concomitant use of intravenous acetaminophen and diclofenac suppository on pain severity reduction and reducing the need for repeated doses of narcotics and prolonging the postoperative analgesia.


Molecular Engineering of 2D Nanomaterial Field-Effect Transistor Sensors: Fundamentals and Translation across the Innovation Spectrum.
Over the last decade, 2D layered nanomaterials have attracted significant attention across the scientific community due to their rich and exotic properties. Various nanoelectronic devices based on these 2D nanomaterials have been explored and demonstrated, including those for environmental applications. Here, the fundamental attributes of 2D layered nanomaterials for field-effect transistor (FET) sensors and tunneling FET (TFET) sensors, which provide versatile detection of water contaminants such as heavy-metal ions, bacteria, nutrients, and organic pollutants, are discussed. The major challenges and opportunities are also outlined for designing and fabricating 2D nanomaterial FET/TFET sensors with superior performance. Translation of these FET/TFET sensors from fundamental research to applied technology is illustrated through a case study on graphene-based real-time FET water sensors. A second case study centers on large-scale sensor networks for water-quality monitoring to enable intelligent drinking water and river-water systems. Overall, 2D nanomaterial FET sensors have significant potential for enabling a human-centered intelligent water system that can likely be applied to other precarious water supplies around the globe.


Is the incidence of hypospadias increasing? Analysis of Finnish hospital discharge data 1970-1994.
Reports suggesting an increasing incidence of male genitourinary anomalies such as hypospadias, possibly related to environmental factors such as environmental estrogen-like compounds, have recently received considerable publicity. These reports are based on birth defects registry data, and there may be variation in the completeness of the registries used. We analyzed temporal trends in the prevalence of hypospadias in Finland to assess the previously reported low overall prevalence and to detect any possible increasing tendencies during the past decade. We identified all patients who were surgically treated for hypospadias before the age of 9 years among boys born 1970-1986 in the national hospital discharge registry. We calculated the cumulative prevalence by dividing the number of patients by the number of male births, and we used Poisson regression analysis. Out of 549,176 boys born in Finland in 1970-1986, 1,543 were treated for hypospadias by the age of 8 years (28.1 surgically treated patients per 10,000 male live births; 95% confidence interval, 26.7-29.5). The prevalence of hypospadias in Finland remained constant throughout the study period and appears to have been approximately three times higher than previously reported. Changes in completeness of registration may account for a substantial proportion of the reported increases in the prevalence of hypospadias in Finland and possibly also elsewhere.


Changing prevalence of asthma among schoolchildren in Israel.
This survey was part of a health monitoring system operated in the vicinity of a new power plant in Israel. The aim of this analysis was to determine whether a temporal trend of increased prevalence of asthma can be observed among cohorts of same-aged children, between 1980 and 1989. Schoolchildren were followed up between 1980 and 1989. They performed pulmonary function tests (PFTs), and their parents filled out American Thoracic Society-National Heart and Lung Institute (ATS-NHLI) health questionnaires. This report deals with the changes in the prevalence of asthma, related respiratory conditions and PFT in four cross-sectional data sets gathered among eighth-grade schoolchildren (aged 13-14 yrs). A highly significant (p=0.0005) increase in the prevalence of asthma (from 5.6% in 1980 to 11.2% in 1989), and of wheezing accompanied by shortness of breath (p=0.0009) could be observed. A similar trend could not be found for the prevalence of bronchitis among these children. PFTs of children suffering from asthma or from wheeze accompanied by shortness of breath were lower than those of healthy children. Changes in prevalence of background variables over time could not explain these findings. The significant rise in the prevalence of asthma coupled with reduced pulmonary function test results among asthmatic children, seems to reflect a true increase in morbidity. Temporal changes in the prevalence of background variables as well as proximity to the power plant could not explain this trend.


Estimating the prevalence and incidence of multiple system atrophy in the USA: Insights from a national claims database.
Published literature on the prevalence and incidence of multiple system atrophy (MSA) in the US are scarce or based on relatively older studies. The objective of this study was to estimate the prevalence and cumulative incidence of MSA in the US. This was a retrospective study of individuals aged 30 years or older in a large US claims database from 2016 to 2021. The primary endpoint was ≥1 MSA claim. Persons with ≥2 MSA claims were also examined. Incident cases aged ≥30 years with a minimum of one-year of continuous enrollment prior to and following cohort entry were identified. Prevalence and cumulative incidence of MSA were estimated for year 2021 and were also standardized to the 2021 US population. The crude prevalence of MSA was 7.2 per 100,000 persons in 2021 and increased with age. After standardization to the US population, the age-adjusted prevalence was 12.4 per 100,000 translating to 41,133 persons in the 2021 US population. In persons with ≥2 MSA claims, the crude and age-adjusted prevalence were 3.1 and 5.7 per 100,000 persons. The crude cumulative incidence of MSA for individuals aged 30 years and older was 9.8 per 100,000 persons in 2021. The estimated cumulative incidence of MSA in individuals 30 years or older, age-adjusted to the 2021 U S. population, was 14.2 per 100,000. This study provides real-world evidence on the prevalence and cumulative incidence of MSA in the US to better understand the medical care needs and treatment.


The approximation of image blur restoration filters by finite impulse responses.
Image blur can often be modeled by a linear spatially invariant, symmetric point spread function. For this class of functions, several restoration filters are known in the literature. The approximation of their frequency transfer functions (ftf's) by the ftf's of small finite impulse response (FIR) filters has been studied. Accurate approximations will be possible by 9 × 9 FIR's with 8-bit elements if the approximation is done in a weighted MMSE sense, and if the truncation of the element values will be carried out such that the errors are small. A heuristic truncation algorithm MINIM will be described. An example of restoration by a 9 × 9 FIR will be shown.


The influence of an unilateral carotid artery stenosis on brain oxygenation.
We study the impact of varying degrees of unilateral stenoses of an carotid artery on pulsatile blood flow and oxygen transport from the heart to the brain. For the numerical simulation a model reduction approach is used involving non-linear 1-D transport equation systems, linear 1-D transport equations and 0-D models. The haemodynamic effects of vessels beyond the outflow boundaries of the 1-D models are accounted for using a 0-D lumped three element windkessel model. At the cerebral outflow boundaries the 0-D windkessel model is extended by metabolic autoregulation, based on the cerebral oxygen supply. Additionally lumped parameter models are applied to incorporate the impact of the carotid stenosis. Our model suggests that for a severe unilateral stenosis in the right carotid artery the partial pressure of oxygen in the brain area at risk can only be restored, if the corresponding cerebral resistance is significantly decreased and if the circle of Willis (CoW) is complete.


Medication-wide association studies.
Undiscovered side effects of drugs can have a profound effect on the health of the nation, and electronic health-care databases offer opportunities to speed up the discovery of these side effects. We applied a "medication-wide association study" approach that combined multivariate analysis with exploratory visualization to study four health outcomes of interest in an administrative claims database of 46 million patients and a clinical database of 11 million patients. The technique had good predictive value, but there was no threshold high enough to eliminate false-positive findings. The visualization not only highlighted the class effects that strengthened the review of specific products but also underscored the challenges in confounding. These findings suggest that observational databases are useful for identifying potential associations that warrant further consideration but are unlikely to provide definitive evidence of causal effects.


Estrogen receptor regulation of carbonic anhydrase XII through a distal enhancer in breast cancer.
The expression of carbonic anhydrase XII (CA12), a gene that encodes a zinc metalloenzyme responsible for acidification of the microenvironment of cancer cells, is highly correlated with estrogen receptor alpha (ER alpha) in human breast tumors. Here, we show that CA12 is robustly regulated by estrogen via ER alpha in breast cancer cells, and that this regulation involves a distal estrogen-responsive enhancer region. Upon the addition of estradiol, ER alpha binds directly to this distal enhancer in vivo, resulting in the recruitment of RNA polymerase II and steroid receptor coactivators SRC-2 and SRC-3, and changes in histone acetylation. Mutagenesis of an imperfect estrogen-responsive element within this enhancer region abolishes estrogen-dependent activity, and chromosome conformation capture and chromatin immunoprecipitation assays show that this distal enhancer communicates with the transcriptional start site of the CA12 gene via intrachromosomal looping upon hormone treatment. This distal enhancer element is observed in the homologous mouse genomic sequence, and the expression of the mouse homologue, Car12, is rapidly and robustly stimulated by estradiol in the mouse uterus in vivo, suggesting that the ER regulation of CA12 is mechanistically and evolutionarily conserved. Our findings highlight the crucial role of ER in the regulation of the CA12 gene, and provide insight into the transcriptional regulatory mechanism that accounts for the strong association of CA12 and ER in human breast cancers.


Continuous lateral rotational therapy in trauma-A systematic review and meta-analysis.
The purpose of this study was to evaluate the impact of continuous lateral rotational therapy (CLRT) on respiratory complications and mortality in patients suffering from trauma. The literature databases PubMed®/Medline® and the Cochrane Library® were systematically searched for prospective controlled trials comparing continuous lateral rotational therapy to conventional manual positioning in trauma patients. A total of 8 publications (n= 422 patients) with comparable age and injury severity were included in the meta-analysis. A significant reduction in the incidence of nosocomial pneumonia (OR: 0.33, [95%CI: 0.17, 0.65], p=0.001) was observed in patients treated prophylactically with continuous lateral rotational therapy. When used with therapeutic intention, CLRT had no impact on the incidence of pneumonia. There were no significant differences in mortality, duration of mechanical ventilation, or ICU length of stay. Analogous to studies evaluating CLRT in medical or mixed patient collectives, CLRT reduced the rates of nosocomial pneumonia in trauma patients. This, however, had no impact on overall mortality. The level of evidence of the studies included was limited by several factors. An adequately powered, well-designed multi-centre randomised controlled trial is required, to validly assess the utility of CLRT for the prevention and treatment of pulmonary complications in patients suffering from trauma. Systematic review and meta-analysis, level III.


Stability assessment of gas mixtures containing terpenes at nominal 5 nmol/mol contained in treated aluminum gas cylinders.
Studies of climate change increasingly recognize the diverse influences exerted by terpenes in the atmosphere, including roles in particulates, ozone formation, and their oxidizing potential. Measurements of key terpenes suggest atmospheric concentrations ranging from low pmol/mol (parts per trillion) to nmol/mol (parts per billion), depending on location and compound. To accurately establish concentration trends, assess the role of terpenes in atmospheric chemistry, and relate measurement records from many laboratories and researchers, it is essential to have good calibration standards. The feasibility of preparing well-characterized, stable gas cylinder standards for terpenes at the nmol/mol level is not yet well established. Several of the world's National Metrology Institutes (NMIs) are researching the feasibility of developing primary and secondary reference gas standards at the nmol/mol level for terpenes. The US NMI, the National Institute of Standards and Technology, has prepared several nmol/mol mixtures, in treated aluminum gas cylinders, containing terpenes in dry nitrogen at nominal 5 nmol/mol for stability studies. Overall, 11 terpenes were studied for stability. An initial gas mixture containing nine terpenes, one oxygenate, and six aromatic compounds, including benzene as an internal standard, was prepared. Results for four of the nine terpenes in this initial mixture indicate stability in these treated aluminum gas cylinders for over 6 months and project long term (years) stability. Interesting results were seen for beta-pinene, which when using a linear equation rate decline predicts that it will reach a zero concentration level at day 416. At the same time, increases in alpha-pinene, D: -limonene (R-(+)-limonene), and p-cymene were observed, including camphene, a terpene not prepared in the gas mixture, indicating a chemical transformation of beta-pinene to these species. Additional mixtures containing combination of either alpha-pinene, camphor, alpha-terpinene, and benzene indicate a second-order quadratic rate decline for the alpha-pinene and alpha-terpinene, a linear rate decline for camphor, and a second-order quadratic rate increase of camphene.


Decline in Left Ventricular Ejection Fraction Following Anthracyclines Predicts Trastuzumab Cardiotoxicity.
The aim of CATS (Cardiotoxicity of Adjuvant Trastuzumab Study) was to prospectively assess clinical, biochemical, and genomic predictors of trastuzumab-related cardiotoxicity (TRC). Cardiac dysfunction is a common adverse effect of trastuzumab. Studies to identify predictive biomarkers for TRC have enrolled heterogeneous populations and yielded mixed results. A total of 222 patients with early-stage human epidermal growth factor receptor 2-positive breast cancer scheduled to receive adjuvant anthracyclines followed by 12 months of trastuzumab were prospectively recruited from 17 centers. Left ventricular ejection fraction (LVEF), troponin T, and N-terminal prohormone of brain natriuretic peptide were measured at baseline, post-anthracycline, and every 3 months during trastuzumab. Germline single-nucleotide polymorphisms in ERBB2, FCGR2A, and FCGR3A were analyzed. TRC was defined as symptomatic heart failure; cardiac death, arrhythmia, or infarction; a decrease in LVEF of >15% from baseline; or a decrease in LVEF of >10% to <50%. TRC occurred in 18 of 217 subjects (8.3%). Lower pre-anthracycline LVEF and greater interval decline in LVEF from pre- to post-anthracycline were each associated with TRC on multivariate analyses (odds ratio: 3.9 [p = 0.0001] and 7.9 [p < 0.0001] for a 5% absolute change in LVEF). Higher post-anthracycline N-terminal prohormone of brain natriuretic peptide level was associated with TRC on univariate but not multivariate analyses. There were no associations between troponin T or ERBB2/FGCR polymorphisms and TRC. Baseline LVEF and LVEF change post-anthracycline were used to generate a "low-risk TRC score" to identify patients with low TRC incidence. Low baseline LVEF and greater LVEF decline post-anthracycline were both independent predictors of TRC. The other biomarkers did not further improve the ability to predict TRC. (Cardiotoxicity of Adjuvant Trastuzumab [CATS]; NCT00858039).


Objective response by mRECIST as a predictor and potential surrogate end-point of overall survival in advanced HCC.
The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was developed to overcome the limitations of standard RECIST criteria in response assessment of hepatocellular carcinoma (HCC). We aimed to investigate whether objective response by mRECIST accurately predicted overall survival (OS) in patients with advanced HCC treated with systemic targeted therapies and also to preliminarily assess this end-point as a potential surrogate of OS. Individual patient data from the BRISK-PS randomized phase III trial comparing brivanib vs. placebo (the first to prospectively incorporate mRECIST) were used to analyze objective response as a predictor of OS in a time-dependent covariate analysis. Patients with available imaging scans during follow-up were included (n=334; 85% of those randomized). Moreover, a correlation of the survival probability in deciles vs. the observed objective response was performed to evaluate its suitability as a surrogate end-point. Objective response was observed in 11.5% and 1.9% of patients treated with brivanib and placebo respectively, and was associated with a better survival (median OS 15.0 vs. 9.4months, p<0.001). In addition, objective response had an independent prognostic value (HR=0.48; 95% confidence interval [CI], 0.26-0.91, p=0.025) along with known prognostic factors. Finally, objective response showed promising results as a surrogate of OS in this trial (R=-0.92; 95% CI, -1 to -0.73, p<0.001). It was an early indicator of the treatment effect (median time to objective response was 1.4months). Objective response by mRECIST in advanced HCC predicts OS and thus can be considered as a candidate surrogate end-point. Further studies are needed to support this finding. There is a need to identify surrogate end-points for overall survival in advanced hepatocellular carcinoma. We studied patients from the phase III BRISK trial, comparing brivanib treatment with placebo after sorafenib progression. We demonstrate that objective response is an independent predictor of survival and qualifies as a potential surrogate end-point for overall survival in this patient population. NCT00825955.


Antifungal mono- and dimeric nitrogenous bisabolene derivatives from a sponge in the order Bubarida from Futuna Islands.
An abundant sponge of the order Bubarida was selected for further chemical investigation following biological and chemical screening of sponges collected from Futuna Islands in the Indo-Pacific. Ten new nitrogenous bisabolene derivatives were isolated and identified: the monomeric theonellin formamide analogues named bubaridins A-F (1-6) with unusual oxidised linear chains, and the first isocyanide/formamide dimeric and cyclised bisabolenes 7-9. The structure elucidation of these nitrogenous bisabolenes involved HRESIMS, NMR, and ECD analyses, and the chiral compounds were found to be racemates. A biosynthetic hypothesis for the production of these metabolites is proposed and some chemotaxonomic considerations are discussed. Furthermore, the antimicrobial and antitumoral activity were evalutated and the trans-dimer theonellin isocyanide (7) was shown to exhibit potent and selective antifungal activity.


Clinical significance of the interaction between lithium and a neuromuscular blocker.
Reports of delayed recovery from anesthesia by patients concurrently receiving lithium carbonate and a neuromuscular blocker have been followed by a recommendation to avoid such a combination and, hence, concurrent treatment with lithium and electroconvulsive therapy (ECT). The authors review the literature and their clinical experience with such a drug combination at one psychiatric hospital. They conclude that the clinical and experimental findings to date are insufficient to warrant proscribing the combination of lithium and ECT on the basis of possible potentiation of neuromuscular blockade by lithium.


The intriguing effect of ethanol and nicotine on acetylcholine-sensitive potassium current IKAch: Insight from a quantitative model.
Recent experimental work has revealed unusual features of the effect of certain drugs on cardiac inwardly rectifying potassium currents, including the constitutively active and acetylcholine-induced components of acetylcholine-sensitive current (IKAch). These unusual features have included alternating susceptibility of the current components to activation and inhibition induced by ethanol or nicotine applied at various concentrations, and significant correlation between the drug effect and the current magnitude measured under drug-free conditions. To explain these complex drug effects, we have developed a new type of quantitative model to offer a possible interpretation of the effect of ethanol and nicotine on the IKAch channels. The model is based on a description of IKAch as a sum of particular currents related to the populations of channels formed by identical assemblies of different α-subunits. Assuming two different channel populations in agreement with the two reported functional IKAch-channels (GIRK1/4 and GIRK4), the model was able to simulate all the above-mentioned characteristic features of drug-channel interactions and also the dispersion of the current measured in different cells. The formulation of our model equations allows the model to be incorporated easily into the existing integrative models of electrical activity of cardiac cells involving quantitative description of IKAch. We suppose that the model could also help make sense of certain observations related to the channels that do not show inward rectification. This new ionic channel model, based on a concept we call population type, may allow for the interpretation of complex interactions of drugs with ionic channels of various types, which cannot be done using the ionic channel models available so far.


Risk factors for infection and amputation following open, combat-related calcaneal fractures.
High-energy open calcaneal fractures are severe injuries complicated by high rates of infection, uncertain functional outcomes, and frequent need for later amputation. We conducted a retrospective review of 102 consecutive combat-related open calcaneal fractures. Patient demographics, injury mechanisms, fracture and wound characteristics, associated fractures, and methods of fracture fixation were reviewed to determine risk factors for eventual amputation or infection. Eighty-nine patients, with a mean age of twenty-six years, sustained 102 open calcaneal fractures (thirteen bilateral). After a mean follow-up of four years (range, five to ninety-two months), 42% (forty-three limbs) underwent amputation. A delayed amputation (more than twelve weeks from the time of injury) was performed in 15% (fifteen) of 102 open calcaneal fractures. In a multivariate Cox proportional-hazards survival model with time to amputation as the end point, the blast mechanism of injury, plantar wound location, larger size of open wound (in square centimeters), and escalating Gustilo and Anderson classification types (p < 0.05 for all) were predictive of eventual amputation. At the time of the final follow-up, patients who had undergone amputation had lower visual analogue scale scores for pain (2.1 compared with 4.0; p < 0.0001) and higher Tegner activity levels (5.4 compared with 3.5; p < 0.0001) than limb salvage patients. Lower-extremity amputation following open calcaneal fractures is predicted by the injury mechanism, wound location and size, and open fracture type and severity. After short-term follow-up, patients with open calcaneal fractures eventually requiring amputation exhibit improved pain and activity levels compared with patients with continued, ostensibly successful limb salvage.


Medicinal properties of Ocotea bullata stem bark extracts: phytochemical constituents, antioxidant and anti-inflammatory activity, cytotoxicity and inhibition of carbohydrate-metabolizing enzymes.
This study evaluates the phytochemical constituents, antioxidant and anti-inflammatory activity, cytotoxicity, and inhibitory activity against carbohydrate metabolism of extracts from Ocotea bullata stem bark. Hexane, ethyl acetate, methanol and water were used to extract the air-dried sample. The phytochemical investigation and antioxidant assays were carried out on the extracts using standard procedures. The antidiabetic and anti-inflammatory potentials were evaluated using α-amylase, α-glucosidase and 5-lipoxygenase enzymes respectively. Vero cells were employed to determine the cytotoxicity of the extracts. The ethyl acetate extract showed higher phenolic contents (8.97 mg/g gallic acid) while methanol displayed higher flavonoid (36.06 mg/g quercetin) and flavonol (153.44 mg/g rutin) contents than other extracts. Hexane extract had the greatest capacity to scavenge 1,1-diphenyl-2-picryl-hydrazyl (0.19 mg/mL), hydroxyl (25.77 mg/mL) and 2,2-azino-bis(3-ethylbenzothiazoline)-6-sulfonic acid (0.07 mg/mL) radicals, while ethyl acetate extract exhibited stronger inhibition (P < 0.05) against superoxide anion (0.41 mg/mL) and ferric ion-reducing power (2.36 mg/mL) compared to other extracts and standards. Aqueous extract (27.02 mg/mL) exhibited strong metal-chelating activity (P < 0.05) compared to other extracts and gallic acid. The aqueous extract demonstrated the greatest inhibition of α-glucosidase (1.45 mg/mL) and α-amylase (2.43 mg/mL) compared to other extracts and acarbose. There were no significant differences (P < 0.05) in half-maximum inhibitory concentration (IC50) values of all tested extracts and indomethacin in the inhibition of 5-lipoxygenase activity. The aqueous extract was nontoxic to Vero cells with an IC50 value of 0.38 mg/mL. O. bullata stem bark contains active phytochemicals with diverse pharmacological potentials that could be beneficial in managing diabetes and inflammation.


Use of ethinylestradiol/drospirenone combination in patients with the polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is one of the most common endocrine/metabolic disorders found in women, affecting approximately 105 million women worldwide. It is characterized by ovulatory dysfunction, often presenting as oligomenorrhea or amenorrhea and either clinical or biochemical hyperandrogenism. Combined oral contraceptive (COC) therapy has long been a cornerstone of care for women with PCOS. COC therapy often provides clinical improvement in the areas of excessive hair growth, unpredictable menses, acne, and weight gain. One of the main issues in COC therapy is choosing the most appropriate progestin component to provide the greatest anti androgenic effects. Drospirenone, a relatively new progestin, has shown benefit in the PCOS population when used in conjunction with ethinyl estradiol. We now review the role of COCs in PCOS, focusing specifically on drospirenone. Controversy over metabolic effects of COCs in PCOS is also discussed.


Neuromodulation for Post-Stroke Motor Recovery: a Narrative Review of Invasive and Non‑Invasive Tools.
Stroke remains a leading disabling condition, and many survivors have permanent disability despite acute stroke treatment and subsequent standard-of-care rehabilitation therapies. Adjunctive neuromodulation is an emerging frontier in the field of stroke recovery. In this narrative review, we aim to highlight and summarize various neuromodulation techniques currently being investigated to enhance recovery and reduce impairment in patients with stroke. For motor recovery, repetitive transcranial magnetic simulation (rTMS) and direct current stimulation (tDCS) have shown promising results in many smaller-scale trials. Still, their efficacy has yet to be proven in large-scale pivotal trials. A promising large-scale study investigating higher dose tDCS combined with constraint movement therapy to enhance motor recovery is currently underway. MRI-guided tDCS studies in subacute and chronic post-stroke aphasia showed promising benefits for picture-naming recovery. rTMS, particularly inhibitory stimulation over the contralesional homolog, could represent a pathway forward in post-stroke motor recovery in the setting of a well-designed and adequately powered clinical trial. Recently evidenced-based guideline actually supported Level A (definite efficacy) for the use of low-frequency rTMS of the primary motor cortex for hand motor recovery in the post-acute stage of stroke based on the meta-analysis result. Adjunctive vagal nerve stimulation has recently received FDA approval to enhance upper limb motor recovery in chronic ischemic stroke with moderate impairment, and progress has been made to implement it in real-world practice. Despite a few small and large-scale studies in epidural stimulation (EDS), further research on the utilization of EDS in post-stroke recovery is needed. Deep brain stimulation or stent-based neuromodulation has yet to be further tested regarding safety and efficacy. Adjunctive neuromodulation to rehabilitation therapy is a promising avenue for promoting post-stroke recovery and decreasing the overall burden of disability. The pipeline for neuromodulation technology remains strong as they span from the preclinical stage to the post-market stage. We are optimistic to see that more neuromodulation tools will be available to stroke survivors in the not-to-distant future.


Occupation and multiple myeloma: an occupation and industry analysis.
Multiple myeloma (MM) is an incurable plasma cell malignancy with a poorly understood etiology. The purpose of our research was to examine the relationships between lifetime occupations and MM in a relatively large case-control study. MM cases (n = 180) were identified through cancer registries in the Seattle-Puget Sound area and Detroit. Population-based controls (n = 481) were identified using random digit dialing and Medicare and Medicaid Services files. In-person interviews were conducted to ascertain occupational histories. Standard occupational classification (SOC) and standard industrial classification (SIC) codes were assigned to each job held by each participant. Unconditional logistic regression was used to generate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between MM and having ever worked in each occupation/industry and according to duration of employment in an occupation/industry. The risk of MM was associated with several manufacturing occupations and industries, including machine operators and tenders, not elsewhere classified (SOC 76) (OR = 1.8, CI = 1.0-3.3); textile, apparel, and furnishing machine operators and tenders (SOC 765) (OR = 6.0, CI = 1.7-21); and machinery manufacturing, except electrical (SIC 35) (OR = 3.3, CI = 1.7-6.7). Several service occupations and industries, such as food and beverage preparation (SOC 521) (OR = 2.0, CI = 1.1-3.8), were also associated with MM. One occupation that has been associated with MM in several previous studies, painters, paperhangers, and plasterers (SOC 644) was associated with a non-significantly elevated risk (OR = 3.6, CI = 0.7-19). We found associations between the risk of MM and employment in several manufacturing and service-related occupations and industries.


The NADPH metabolic network regulates human αB-crystallin cardiomyopathy and reductive stress in Drosophila melanogaster.
Dominant mutations in the alpha-B crystallin (CryAB) gene are responsible for a number of inherited human disorders, including cardiomyopathy, skeletal muscle myopathy, and cataracts. The cellular mechanisms of disease pathology for these disorders are not well understood. Among recent advances is that the disease state can be linked to a disturbance in the oxidation/reduction environment of the cell. In a mouse model, cardiomyopathy caused by the dominant CryAB(R120G) missense mutation was suppressed by mutation of the gene that encodes glucose 6-phosphate dehydrogenase (G6PD), one of the cell's primary sources of reducing equivalents in the form of NADPH. Here, we report the development of a Drosophila model for cellular dysfunction caused by this CryAB mutation. With this model, we confirmed the link between G6PD and mutant CryAB pathology by finding that reduction of G6PD expression suppressed the phenotype while overexpression enhanced it. Moreover, we find that expression of mutant CryAB in the Drosophila heart impaired cardiac function and increased heart tube dimensions, similar to the effects produced in mice and humans, and that reduction of G6PD ameliorated these effects. Finally, to determine whether CryAB pathology responds generally to NADPH levels we tested mutants or RNAi-mediated knockdowns of phosphogluconate dehydrogenase (PGD), isocitrate dehydrogenase (IDH), and malic enzyme (MEN), the other major enzymatic sources of NADPH, and we found that all are capable of suppressing CryAB(R120G) pathology, confirming the link between NADP/H metabolism and CryAB.


Factors affecting the incidence of infection in hip and knee replacement: an analysis of 5277 cases.
Infection remains a significant and common complication after joint replacement and there is debate about which contributing factors are important. Few studies have investigated the effect of the operating time on infection. We collected data prospectively from 5277 hip and knee replacements which included the type of procedure, the operating time, the use of drains, the operating theatre, surgeon, age and gender. In a subgroup of 3449 knee replacements further analysis was carried out using the tourniquet time in place of the operating time. These variables were assessed by the use of generalised linear modelling against superficial, deep or joint-space post-operative infection as defined by the Australian Surgical-Site Infection criteria. The overall infection rate was 0.98%. In the replacement data set both male gender (z = 3.097, p = 0.00195) and prolonged operating time (z = 4.325, p < 0.001) were predictive of infection. In the knee subgroup male gender (z = 2.250, p = 0.02447), a longer tourniquet time (z = 2.867, p = 0.00414) and total knee replacement (versus unicompartmental knee replacement) (z = -2.052, p = 0.0420) were predictive of infection. These findings support the view that a prolonged operating time and male gender are associated with an increased incidence of infection. Steps to minimise intra-operative delay should be instigated, and care should be exercised when introducing measures which prolong the duration of joint replacement.


Measurement of minimum substrate concentration (Smin) in a recycling fermentor and its prediction from the kinetic parameters of Pseudomonas strain B13 from batch and chemostat cultures.
The minimum substrate concentration required for growth, Smin, was measured for Pseudomonas sp. strain B13 with 3-chlorobenzoate (3CB) and acetate in a recycling fermentor. The substrates were provided alone or in a mixture. Smin values predicted with kinetic parameters from resting-cell batches and chemostat cultures differed clearly from the values measured in the recycling fermentor. When 3CB and acetate were fed as single substrates, the measured Smin values were higher than the individual Smin values in the mixture. The Smin in the mixture reflected the relative energy contributions of the two substrates in the fermentor feed. The energy-based maintenance coefficients during zero growth in the recycling fermentor were comparable for all influent compositions (mean +/- standard deviation, 0.34 +/- 0.07 J mg [dry weight]-1 h-1). Maintenance coefficient values for acetate were significantly higher in chemostat experiments than in recycling-fermentor experiments. 3CB maintenance coefficients were comparable in both experimental systems. The parameters for 3CB consumption kinetics varied remarkably with the experimental growth conditions in batch, chemostat, and recycling-fermentor environments. The results demonstrate that the determination of kinetic parameters in the laboratory for prediction of microbial activity in complex natural systems should be done under conditions which best mimic the system under consideration.


Heparin-Binding Epidermal Growth Factor-Like Growth Factor as a Potent Target for Breast Cancer Therapy.
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) belongs to the EGF family and exhibits its activity after binding to its receptors in autocrine, paracrine, and juxtacrine interactions. HB-EGF plays important roles in several biological and pathological processes, such as wound healing, blastocyst implantation, atherosclerosis, and heart development. Clinical studies have shown that HB-EGF is closely correlated with tumorigenesis, metastasis, and drug resistance in breast cancer. Specifically, targeted inhibition of HB-EGF improves the therapeutic efficacy and suppresses the tumor progression. This review discusses the importance of HB-EGF in mammary carcinoma progression and the potential value of HB-EGF as a therapeutic target for breast cancer treatment.


How to use multi-criteria decision analysis methods for reimbursement decision-making in healthcare: a step-by-step guide.
In recent years, the quest for more comprehensiveness, structure and transparency in reimbursement decision-making in healthcare has prompted the research into alternative decision-making frameworks. In this environment, multi-criteria decision analysis (MCDA) is arising as a valuable tool to support healthcare decision-making. In this paper, we present the main MCDA decision support methods (elementary methods, value-based measurement models, goal programming models and outranking models) using a case study approach. For each family of methods, an example of how an MCDA model would operate in a real decision-making context is presented from a critical perspective, highlighting the parameters setting, the selection of the appropriate evaluation model as well as the role of sensitivity and robustness analyses. This study aims to provide a step-by-step guide on how to use MCDA methods for reimbursement decision-making in healthcare.


Diverticulum of the midthoracic oesophagus and left diaphragmatic relaxation.
The case of a 58-year-old man with a large midthoracic oesophageal diverticulum and a left diaphragmatic relaxation who presented with night regurgitations, abdominal bloating, epigastric burning and a sensation of fullness after meals is reported. The patient underwent a successful thoracotomic diverticulectomy with left diaphragmatic plicature. The postoperative course was uneventful. To our knowledge this is the first reported case of an association between midthoracic oesophageal diverticulum and left diaphragmatic relaxation. Moreover, we hypothesised that the diverticulum was caused by a pulsion mechanism due to obstruction of the distal oesophagus secondary to diaphragmatic relaxation.


miR-30a suppresses cell migration and invasion through downregulation of PIK3CD in colorectal carcinoma.
MicroRNAs (miRNAs) play key roles in tumor metastasis. The aim of this study was to determine the regulation and function of miR-30a in colorectal carcinoma (CRC) metastasis. The expression of miR-30a was detected in CRC cell lines and samples by qRT-PCR. The anti-metastatic effect of miR-30a was determined by both in vitro and in vivo assays. A luciferase reporter assay was performed to determine target association between miR-30a and phosphoinositide 3-kinase catalytic subunit delta (PIK3CD). miR-30a was significantly downregulated in highly metastatic CRC cell lines and metastatic tissues. Overexpression of miR-30a suppressed CRC cell migration and invasion in vitro and liver metastasis in vivo, whereas miR-30a deletion dramatically promoted cell migration and invasion. Further studies revealed that PIK3CD is a direct target of miR-30a as miR-30a bounds directly to the 3'-UTR of PIK3CD, subsequently reducing its expression. Similar to the restoring miR-30a expression, PIK3CD downregulation inhibited cell migration and invasion, whereas PIK3CD overexpression rescued the suppressive effect of miR-30a. Moreover, significant downregulation of miR-30a in metastatic CRC tissues was found to be inversely correlated with PIK3CD expression. Mechanistic studies revealed that miR-30a down-regulated the expression of key components of the Akt/mTOR pathway, whereas PIK3CD overexpression reversed this negative effect. Our findings indicate that miR-30a might function as a metastasis suppressor in CRC. miR-30a may be a potential therapeutic target to block CRC metastasis.


Recent trends in incidence and mortality of oral and pharyngeal cancer in Schleswig-Holstein in Northern Germany.
Oral and pharyngeal cancer is still a serious public health problem with more than 10,000 new cases every year in Germany, more than 4,000 patients die of this tumour each year. Aim of the project was a detailed analysis on incidence and mortality rates by age, gender and tumour sites in Northern Germany. The data on incidence and mortality rates from the population-based Cancer Registry of Schleswig-Holstein in Northern Germany were evaluated by age, gender and tumour sites from 2000 to 2006. Some 3,127 new cases of oral and pharyngeal cancer (72% men, 28% women) were registered. About half of all cases were aged 60-79 years. The incidence trends for 40-59 years described a slight decrease. Trends for pharyngeal cancer showed the highest incidence rates for both genders in those aged 60-79. This detailed analysis with subgroups showed interesting differences and revealed considerable variations, especially compared to the increasing trends in several European countries. These population-based data of Schleswig-Holstein showed interesting differences in the trends for incidence and mortality rates for age groups and tumour sites within the state and compared to the national German data and revealed noticeable different trends compared to several European countries. This population-based information informs effective cancer control.


Effect of blending and emulsification on thermal behavior, solid fat content, and microstructure properties of palm oil-based margarine fats.
The ability of palm oil (PO) to crystallize as beta prime polymorph has made it an attractive option for the production of margarine fat (MF). Palm stearin (PS) expresses similar crystallization behavior and is considered one of the best substitutes of hydrogenated oils due to its capability to impart the required level of plasticity and body to the finished product. Normally, PS is blended with PO to reduce the melting point at body temperature (37 °C). Lipid phase, formulated by PO and PS in different ratios were subjected to an emulsification process and the following analyses were done: triacylglycerols, solid fat content (SFC), and thermal behavior. In addition, the microstructure properties, including size and number of crystals, were determined for experimental MFs (EMFs) and commercial MFs (CMFs). Results showed that blending and emulsification at PS levels over 40 wt% significantly changed the physicochemical and microstructure properties of EMF as compared to CMF, resulting in a desirable dipalmitoyl-oleoyl-glycerol content of less than 36.1%. SFC at 37 °C, crystal size, crystal number, crystallization, and melting enthalpies (ΔH) were 15%, 5.37 μm, 1425 crystal/μm(2), 17.25 J/g, and 57.69J/g, respectively. All data reported indicate that the formation of granular crystals in MFs was dominated by high-melting triacylglycerol namely dipalmitoyl-oleoyl-glycerol, while the small dose of monoacylglycerol that is used as emulsifier slowed crystallization rate. Practical Application: Most of the past studies were focused on thermal behavior of edible oils and some blends of oils and fats. The crystallization of oils and fats are well documented but there is scarce information concerning some mechanism related to crystallization and emulsification. Therefore, this study will help to gather information on the behavior of emulsifier on crystallization regime; also the dominating TAG responsible for primary granular crystal formations, as well as to determine the best level of stearin to impart the required microstructure properties and body to the finished products.


High-producing MBL2 genotypes increase the risk of acute and chronic carditis in patients with history of rheumatic fever.
Rheumatic fever (RF) and its most severe sequela, chronic rheumatic heart disease (CRHD), are mediated by an abnormal immunological host response following a Streptococcus pyogenes oropharyngeal infection. Mannan-binding lectin (MBL), a collectin that activates complement, binds to N-acetylglucosamine, a molecule present on the streptococcus cell wall and on human heart valves. As high levels of MBL and MBL2 associated genotypes have previously been seen to be associated with CRHD, we investigated the association between MBL2 polymorphisms and the presence of acute carditis and arthritis in patients with a history of RF. Polymorphisms in exon 1 and in the X/Y promoter region of the MBL2 gene were determined by PCR-SSP in 149 patients with a history of RF and 147 controls. Genotypes associated with the high production of MBL (YA/YA and YA/XA) were more frequent in the patients with acute (26/35, 74%) and chronic carditis (79/107, 74%) when compared to the controls (79/147, 54%; OR 2.48, 95% CI 1.09-5.67, p=0.035 and OR 2.42, 95% CI 1.41-4.16, p=0.001, respectively). Logistic regression analysis showed that MBL levels >2,800 ng/ml increased the risk of CRHD (OR 2.91, 95% CI 1.41-6.03, p=0.003). Among the RF patients without cardiac sequela, YA/YA and YA/XA genotypes were significantly associated with acute carditis when compared to the patients without this clinical manifestation (26/28, 93% vs. 9/14, 64%, OR 7.22, 95% CI 1.18-43.98, p=0.031); on the other hand, arthritis was more frequently observed in those patients presenting MBL2 genotypes related to the low production of MBL (10/14, 71% vs. 10/28, 36%; p=0.048, OR 0.22, 95% CI 0.05-0.89). We concluded that MBL2 genotypes associated with the high production of MBL seem to be involved in the pathogenesis of rheumatic carditis and its progression to CRHD.


A human centrosomal protein is immunologically related to basal body-associated proteins from lower eucaryotes and is involved in the nucleation of microtubules.
Isolation of centrosomes from human cells has revealed a proteic pattern which is both complex and specific. As the most prominent structural element of centrosomes in animal cells, the centriole which is present as two copies, is a highly conserved structure, we have attempted to identify centrosomal proteins on the basis of immunocross-reaction with proteins identified in basal bodies from lower eucaryotes. We report that two antibodies, one raised against the Ca(+)-binding protein centrin (Salisbury, J. L., A. T. Baron, B. Surek, and M. Melkonian. 1984. J. Cell Biol. 99:962-970) and the other directed against a 230-kD protein isolated from the infraciliary cytoskeletal lattice of the protozoan Polyplastron m., decorate the centrosome of human cultured cells, and identify one of the major centrosomal components revealed as a doublet of 62/64 kD. Moreover the nucleation reaction of microtubules, which can be efficiently produced on isolated centrosomes, is blocked by the antibodies, a result which strongly implicates the 62/64-kD protein in this centrosomal activity. We also show that the 62/64-kD protein remains insoluble in conditions (0.5 M KI or 8 M urea) which are capable of extracting most of the centrosomal proteins. Immunocytochemical localization by EM of isolated centrosomes revealed the association of this 62/64-kD doublet with the intercentriolar link and the pericentriolar lattice. Our results suggest that conservation of structure in the centrosome from divergent organisms could be matched by conservation of proteins and activity, evidence for the maintenance of a specific function, which could involve Ca2+, associated with the microtubule organizing centers.


Prenatal diagnosis and fetal therapy of congenital cystic adenomatoid malformation type I of the lung: a report of five cases.
We experienced five pregnancy cases with type I congenital cystic adenomatoid malformation (CCAM) of fetuses and summarized here their clinical characteristics, pregnancy outcomes, and fetal therapies. Four of five cases were prenatally diagnosed using magnetic resonance imaging (MRI) as having lung abnormality, and the remaining case was prenatally diagnosed as having congenital diaphragmatic herniation (CDH). One fetus underwent the puncture of cysts in the lung, and two fetuses received in utero thoracoshunts between cysts and the amniotic fluid cavity (thoracoamniotic shunt). One pregnancy ended in artificial termination at 17 gestational weeks, and 4 pregnancies succeeded in live births. All these 4 infants underwent surgical operations for CCAM, and 1 infant underwent an additional operation for CDH. The MRI examinations were useful to prenatally identify CCAM, and the in utero thoracoamniotic shunt appears to be beneficial in preventing lung hypoplasia in the affected fetuses.


Towards High-Throughput Chemobehavioural Phenomics in Neuropsychiatric Drug Discovery.
Identifying novel marine-derived neuroactive chemicals with therapeutic potential is difficult due to inherent complexities of the central nervous system (CNS), our limited understanding of the molecular foundations of neuro-psychiatric conditions, as well as the limited applications of effective high-throughput screening models that recapitulate functionalities of the intact CNS. Furthermore, nearly all neuro-modulating chemicals exhibit poorly characterized pleiotropic activities often referred to as polypharmacology. The latter renders conventional target-based in vitro screening approaches very difficult to accomplish. In this context, chemobehavioural phenotyping using innovative small organism models such as planarians and zebrafish represent powerful and highly integrative approaches to study the impact of new chemicals on central and peripheral nervous systems. In contrast to in vitro bioassays aimed predominantly at identification of chemicals acting on single targets, phenotypic chemobehavioural analysis allows for complex multi-target interactions to occur in combination with studies of polypharmacological effects of chemicals in a context of functional and intact milieu of the whole organism. In this review, we will outline recent advances in high-throughput chemobehavioural phenotyping and provide a future outlook on how those innovative methods can be utilized for rapidly screening and characterizing marine-derived compounds with prospective applications in neuropharmacology and psychosomatic medicine.


Reduced expression of the vesicular acetylcholine transporter causes learning deficits in mice.
Storage of acetylcholine in synaptic vesicles plays a key role in maintaining cholinergic function. Here we used mice with a targeted mutation in the vesicular acetylcholine transporter (VAChT) gene that reduces transporter expression by 40% to investigate cognitive processing under conditions of VAChT deficiency. Motor skill learning in the rotarod revealed that VAChT mutant mice were slower to learn this task, but once they reached maximum performance they were indistinguishable from wild-type mice. Interestingly, motor skill performance maintenance after 10 days was unaffected in these mutant mice. We also tested whether reduced VAChT levels affected learning in an object recognition memory task. We found that VAChT mutant mice presented a deficit in memory encoding necessary for the temporal order version of the object recognition memory, but showed no alteration in spatial working memory, or spatial memory in general when tested in the Morris water maze test. The memory deficit in object recognition memory observed in VAChT mutant mice could be reversed by cholinesterase inhibitors, suggesting that learning deficits caused by reduced VAChT expression can be ameliorated by restoring ACh levels in the synapse. These data indicate an important role for cholinergic tone in motor learning and object recognition memory.


Home medication and microbiological profile in chronic otitis media in some Nigerian children.
The relationship of home medication to the pathology and microbiological profiles of chronic otitis media was studied in 135 children with middle ear infections. Middle ear lesions were examined and sample obtained for microscopy and culture for bacterial and fungal pathogens. Of a total 115 patients who received home treatment, mostly with extracts of a local herb, Cleome ciliata and unprescribed antibiotics, 111 (96.5 pc) had chronic otitis media with purulent effusion (OME), compared with 11 (55 pc) otitis media (OM) cases among 20 patients who had not received such treatments (p less than 0.05). Staphylococcus aureus and Pseudomonas spp. were the predominant isolates; the latter were the sole infecting agents in 41 episodes and occurred in 10 co-infections. Sensitivity pattern of bacterial isolates indicated that a large proportion of infections would respond to empiric treatment with gentamicin in anticipation of laboratory results on sensitivity tests. This report suggests further studies to define the significance of these medications in the pathogenesis of chronic OME in Nigerian children.


The association of psychiatric diagnosis with weather conditions in a large urban homeless sample.
Assessment of psychiatric disorders encounters unique complexities in homeless populations. Although the use of structured diagnostic instruments has significantly improved research methodology in this area, questions remain about the validity of using cross-sectional diagnostic methods derived from studies of more general populations. In particular, the validity of structured diagnostic instruments in the assessment of schizophrenia, depression, drug use disorder, and antisocial personality disorder (ASPD) in homeless populations has been questioned. The purpose of this study was to examine the association of psychiatric diagnoses with the weather. It was hypothesized that self-report of psychiatric illness may be affected by prevailing weather conditions. Nine hundred homeless subjects randomly sampled from St. Louis shelters, day centers, and unsheltered locations were interviewed over a 1-year period. Official average daily temperature and amount of precipitation on the day of each subject's interview were compared with lifetime and current psychiatric diagnoses ascertained by the Diagnostic Interview Schedule. Similar analyses were performed in general population data from the Epidemiologic Catchment Area study. The study found that among homeless men, inclement weather on the day of interview was associated with lifetime and current diagnoses of major depression, lifetime drug use disorder, lifetime diagnosis of ASPD, and current alcohol use disorder. These findings, however, were not present in homeless women and not reflected in the general population. The results, although limited, suggest that weather may confound cross-sectional, standardized methods of psychiatric diagnosis in homeless men. Weather-related factors among homeless men are associated with ascertainment of both lifetime and current diagnosis of major depression, as well as lifetime drug use disorder and ASPD and current alcohol use disorder. Possible interpretations of these findings are discussed, with implications for intervention strategies for psychiatric disorders in the larger context of homelessness and social problems.


Ehlers-Danlos syndrome and wound healing: injury in a collagen disorder.
Ehlers-Danlos syndrome (EDS) is a rare familial disorder affecting the production, quality and strength of collagen. It presents in many forms, and many individuals experience hypermobile joints and soft, elastic skin. When injury occurs, EDS can result in severe bruising, the development of wide open wounds and delayed healing (Babak et al, 2003). In the case discussed, Lilly, a 10-year-old girl, presented with a wide trauma injury to her lower leg. Healing was influenced by the poor collagen production associated with EDS, and the presence of a high bacterial burden that resulted in infection. Manuka honey was used to reduce the level of invading bacilli and stimulate production of collagen. Following this intervention, complete healing was achieved in two weeks. The action of manuka honey appears to be beneficial in the management of complex wounds, and further research is needed to determine its value in EDS. Involvement of Lilly and her family in clinical decision-making and in the production of this article resulted in a growth in understanding for all parties and the development of a relationship that optimized the nurse/patient experience.