Lung Ultrasound to Detect Pneumothorax in Children Evaluated for Acute Chest Pain in the Emergency Department: An Observational Pilot Study.
Spontaneous pneumothorax is a relatively uncommon and poorly studied condition in children. While several protocols have been developed to evaluate the use of lung ultrasound for dyspneic adult patients in the emergency department, no specific guidelines are present for pediatric emergency physicians. We prospectively analyzed children with acute chest pain and clinical suspicion of pneumothorax evaluated at the pediatric emergency department. We consecutively enrolled children aged 5-17 years presenting to the pediatric emergency department with clinically suspected pneumothorax based on sudden onset of acute chest pain. After clinical examination, all children underwent lung ultrasound followed by chest X-ray (reference standard). We enrolled 77 children, of which 13 (16.9%) received a final diagnosis of pneumothorax. The lung point had a sensitivity of 92.3% (95% CI 77.8-100) and a specificity of 100% (95% CI 94.4-100) for the detection of pneumothorax. The "barcode sign" had a sensitivity of 100% (95% CI 75.3-100) and a specificity of 100% (95% CI 94.4-100) for the detection of pneumothorax. Lung ultrasound is highly accurate in detecting or excluding pneumothorax in children with acute chest pain evaluated in the pediatric emergency department. If pneumothorax is suspected, but the lung point is not visible, the barcode sign should always be sought as it could be a form of massive pneumothorax.


Complementation of fission yeast cdc2ts and cdc25ts mutants identifies two cell cycle genes from Drosophila: a cdc2 homologue and string.
We have exploited the universality of the molecular mechanisms that control entry into mitosis to clone the Drosophila melanogaster homologues of fission yeast Schizosaccharomyces pombe cell division control (cdc) genes by the complementation of temperature sensitive mutations. The Drosophila genes were expressed in S.pombe as cDNAs from the SP6 promoter. Successful recovery of complementing plasmids required that we first 'adapt' pooled plasmids from a Drosophila embryonic cDNA library for propagation in fission yeast by introducing an ars1-LEU2 DNA fragment into the vector. This library was introduced into S.pombe cdc2 and cdc25 mutants, and plasmids isolated carrying cDNAs that complement these mutations. The gene that encodes the Drosophila cdc2 homologue maps to a single locus in the Drosophila genome at 31E on chromosome 2. It is expressed maternally to provide mRNA in syncytial embryos, and appears to be zygotically expressed in mitotically active regions of the cellularized embryo. We have isolated two different cDNAs that complement cdc25-22. One corresponds to a transcript of string, previously described as the Drosophila homologue of cdc25, and the other to a gene that has not been previously characterized.


Dynamic properties of round window membrane in guinea pig otitis media model measured with electromagnetic stimulation.
The round window, one of two openings into the cochlea from the middle ear, plays an important role in hearing and is known to be structurally altered during otitis media. However, there have been no published studies systematically describing the changes in biomechanical properties of the round window membrane (RWM) that accompany bacterial otitis media. Here we describe the occurrence of significant changes in the dynamic properties of the RWM between normal guinea pigs and those with acute otitis media (AOM) that are detectable by electromagnetic force stimulation and laser Doppler vibrometry (LDV) measurements. AOM was induced by transbullar injection of streptococcus pneumoniae into the middle ear, and RWM specimens were prepared three days after challenge. Vibration of the RWM induced by coil-magnet coupling was measured by LDV over frequencies of 0.2-40 kHz. The experiment was then simulated in a finite element model, and the inverse-problem solving method was used to determine the complex modulus in the frequency domain and the relaxation modulus in the time domain. Results from 18 ears (9 control ears and 9 AOM ears) established that both the storage modulus and loss modulus of the RWM from ears with AOM were significantly lower than those of RWM from uninfected ears. The average decrease of the storage modulus in AOM ears ranged from 1.5 to 2.2 MPa and the average decrease of the loss modulus was 0.025-0.48 MPa. Our findings suggest that middle ear infection primarily affects the stiffness of the RWM due to the morphological changes that occur in AOM ears. We also conclude that the coil-magnet coupling method for assessment of RWM function may provide a valuable new approach to characterizing the mechanical response of the RWM when reverse driving is selected for middle ear implantable devices. This article is part of a special issue entitled "MEMRO 2012".


Membrane attack complex of complement is not essential for immune mediated demyelination in experimental autoimmune neuritis.
Antibody deposition and complement activation, especially membrane attack complex (MAC) formation are considered central for immune mediated demyelination. To examine the role of MAC in immune mediated demyelination, we studied experimental allergic neuritis (EAN) in Lewis rats deficient in complement component 6 (C6) that cannot form MAC. A C6 deficient Lewis (Lewis/C6-) strain of rats was bred by backcrossing the defective C6 gene, from PVG/C6- rats, onto the Lewis background. Lewis/C6- rats had the same C6 gene deletion as PVG/C6- rats and their sera did not support immune mediated haemolysis unless C6 was added. Active EAN was induced in Lewis and Lewis/C6- rats by immunization with bovine peripheral nerve myelin in complete Freund's adjuvant (CFA), and Lewis/C6- rats had delayed clinical EAN compared to the Lewis rats. Peripheral nerve demyelination in Lewis/C6- was also delayed but was similar in extent at the peak of disease. Compared to Lewis, Lewis/C6- nerves had no MAC deposition, reduced macrophage infiltrate and IL-17A, but similar T cell infiltrate and Th1 cytokine mRNA expression. ICAM-1 and P-selectin mRNA expression and immunostaining on vascular endothelium were delayed in Lewis C6- compared to Lewis rats' nerves. This study found that MAC was not required for immune mediated demyelination; but that MAC enhanced early symptoms and early demyelination in EAN, either by direct lysis or by sub-lytic induction of vascular endothelial expression of ICAM-1 and P-selectin.


Comparisons of prevalence and related factors of depression in middle-aged adults between urban and rural populations in Japan.
Findings of urban-rural differences in the prevalence of depression have been controversial, and few reports have directly compared the related factors of depression between urban and rural areas. The present study aimed to investigate differences between urban and rural areas in Japan with regards to the prevalence of and related factors of depression in middle-aged adults, in order to further understanding of the features of depression in this demographic. We used a multistage, random sampling procedure and mailing method. In total, 5000 participants were recruited from urban and rural areas in Kumamoto Prefecture (2500 in each area). Participants were aged from 40 to 64 years. Depression was assessed using the Center for Epidemiologic Studies Depression scale (CES-D). The prevalence of middle-aged depression was not different between the urban and rural areas. Logistic regression analysis found that being female, living alone, and having a chronic illness were significantly associated with depression in urban-dwelling middle-aged adults. Younger age, sleep disturbance, and financial strain were significantly associated with depression in both urban and rural areas. The definition of depression was based on CES-D scores, without corroborating clinical evaluation. We found no marked differences in the prevalence of middle-aged depression between the urban and rural areas. Some related factors of depression in middle-aged adults differed between urban and rural areas in Japan. Effective intervention programs for middle-aged adults with depression should consider regional differences.


Magnetic-Induced Luminescence from Flexible Composite Laminates by Coupling Magnetic Field to Piezophotonic Effect.
Magnetic-induced luminescence (MIL) is realized via a strain-mediated coupling strategy. MIL composite laminates composed of magnetic actuator and phosphor phases are developed. The MIL performance is tested under low magnetic fields at room temperature. The results provide a novel type of promising luminescent and magnetic material for developing some new concept devices.


Methodology of dietary assessment in athletes: concepts and pitfalls.
Evaluation of an athlete's diet is important in both clinical practice and research. The main purpose of this review is to provide health professionals with guidance regarding the special issues that are likely to be encountered when assessing the dietary intake of sportspersons. A number of methods may be used for the dietary assessment of individuals and/or groups of athletes, including retrospective (diet recall, food-frequency questionnaire, and diet history) and prospective (diet record, duplicate portion) techniques. A 3-4-day estimated diet record is the most widely used approach, but collection of single or multiple diet recalls is also common. Care must be taken, however, to ensure that days of diet monitoring accurately reflect usual food consumption during the period of interest. Under-reporting of habitual energy intake is widespread among athletes, and its magnitude should be carefully addressed when interpreting the results of dietary assessment. Other issues, specifically related to sportspersons, that are often neglected include adequacy of standard portion sizes, frequency of snacking, fluid intake, supplement use, weight-control practices, and seasonality of sport activities and food consumption. There are subtle methodological differences in the dietary assessment of athletes and non-athletes, which, when taken into consideration, may substantially increase the quality of intake data and optimise the outcome of dietary intervention.


An original technique of brachytherapy in the treatment of epidermoid carcinomas of the buccal mucosa.
To report our experience using brachytherapy in buccal mucosa carcinoma with particular attention on the technique of implantation used and on the elective treatment to the lymph nodes. From 1973 to 1991, 42 patients (36 T1 T2 T3, 35 NO) were treated for epidermoid carcinoma of the buccal mucosa as the first site of head and neck cancer. To study the local control, the group of 36 T1-3 patients was divided into two groups according to the brachytherapy technique used: the parallel wires technique and the loop technique (M. Pernot). The latter consists of making a loop of Iridium wire encircling the tumor, the curved part acting as a barrier for the posterior part of the cheek (site of recurrence). The group of 35 NO patients was individualized to evaluate the necessity of an elective node treatment. Twenty-three patients had no elective treatment to node areas, 8 an external radiotherapy, and 4 a neck dissection. Overall survival of these 42 patients was 63% at 2 years and 47.5% at 5 years. Specific survival was 77.5% at 2 years and 73.6% at 5 years. Survival without recurrence was 58% at 2 years and 54% at 5 years. Eighty-three percent of the recurrences occurred during the first year. There were six local recurrences on the 14 T1-3 patients treated with the parallel wires technique and 1 on the 22 T1-3 patients treated with the loop technique (6 out of 7 in the posterior part of the buccal mucosa). The local control at 5 years was 91% with the loop technique vs. 58% with the parallel wires technique (p = 0.01). Among the 23 NO patients with no elective treatment, 6 had a nodal failure (5 T2 and 1 T1 of 2 cm). Out of the 8 NO patients treated by radiotherapy, 3 had a nodal failure. The four NO patients treated by surgery were controlled. Brachytherapy using the loop technique is the local treatment of choice for tumors < or = 5 cm. Elective treatment of the neck lymph nodes is required in patients with a lesion > 1 cm and neck dissection may be preferable to external radiotherapy.


An autopsy case of sudden unexpected death of a young adult with progressive intraventricular conduction delay.
Herein, we describe an autopsy case of the sudden unexpected death of a 23-year-old man. Retrospective analysis of electrocardiograms revealed progressive widening of the QRS interval. Autopsy showed mild mitral valve prolapse and hypertrabeculation of the left ventricle. Microscopic examination revealed very scarce but considerable minimal myocardial necrotic foci in the left ventricle, and a marked reduction in conduction fibers in the left branch. These findings may be associated with intraventricular conduction delay. Genetic investigation revealed four rare possibly pathogenic variants, including the Emery-Dreifuss muscular dystrophy-associated genetic variant SYNE2_p.A6155 V that is evaluated as pathogenic by most in silico predictive tools. The other possibly pathogenic variants detected were PLEC_p.P973L, TTN_p.I22171T, and p.A12216T. Although these variants are reported to have uncertain significance in the guidelines of the American College of Medical Genetics and Genomics, progressive conduction delay may have been associated with vulnerability of myocytes due to Emery-Dreifuss muscular dystrophy-associated genetic variants in the present case. Younger individuals with progressive conduction delay may require medical work-up and genetic investigation, even if they have no other clinical signs and no or mild structural heart disease.


Isolated primary bone tumours of the lesser trochanter: Demographics, diagnosis and management.
Primary bone tumours arising from the lesser trochanter (LT) are rare and the literature describing them is sparse. In this paper, we describe the largest series of LT tumours describing the demographics, diagnosis and management. A retrospective search of prospectively maintained radiology and oncology databases was performed to identify bone tumours of the LT diagnosed between 2007 and 2018. Metastatic lesions were excluded. All cases were re-reviewed by a senior Radiologist and all case of isolated tumours of the LT were included. 23 cases of isolated LT tumours were identified. There were 15 males and 8 females. Mean age of our cohort was 32 (14-63) years. Most (n = 19, 82.6%) cases had classic radiological (Radiographic, MR Imaging and CT) features and therefore did not undergo biopsy. 4 patients had equivocal radiological investigations that required biopsy to confirm the diagnosis. MR imaging was the most commonly used imaging modality for diagnosis (n = 17, 73.9%)There was a broad range of tumour subtypes, and osteochondroma (n = 17, 73.9%) the most frequently diagnosed. Surgical excision was performed in 4 patients (all osteochondromas) and 4 patients underwent therapeutic radiological guided hip injections for symptomatic relief. The remaining cases were managed conservatively and where they were identified incidentally, no intervention was required. We report the largest case series of isolated primary bone tumours of the LT. All isolated primary bone tumours of LT are benign. Osteochondroma is the most common. The diagnosis can be made with on radiological investigations in most patients.


Use of self-monitoring tools in a clinic sample of adults with type 2 diabetes.
Self-monitoring is an effective strategy for chronic disease management; many readily available mobile applications allow tracking of diabetes-related health behaviors but their use has not yet been integrated into routine clinical care. How patients engage with these applications in the real world is not well understood. The specific aim of this study is to survey adults with type 2 diabetes (T2D) regarding self-monitoring behaviors, including mobile application use. In 2015, we surveyed an adult diabetes clinic population (n = 96) regarding self-monitoring behaviors: diet, physical activity, weight, and blood glucose. Self-monitoring with any method ranged from 20-90 %. About half of the participants owned smartphones; few had mobile applications. The most common app-tracked behavior was physical activity, then weight and diet. Despite numerous available mobile health-tracking applications, few T2D adults from our sample used them, though many reported self-monitoring with other methods.


Polychlorinated terphenyls (PCTs) use, levels and biological effects.
Polychlorinated terphenyls (PCTs) have almost identical characteristics to high chlorinated PCBs: extremely stable, bioaccumulable and biomagnification through food webs might take place. PCT is especially used in investment casting waxes and as a substitute for PCB. In spite of the limited use until now, PCT has been detected in a great variety of environmental samples such as soil, water, shellfish, fish, seals, birds and terrestrial animals. Furthermore, it has been found in paper products and foodstuffs. PCT residues in human tissues--blood, liver, fat and milk--have been detected in some countries. Animal experiments have shown that long-term toxic effects of PCT are of most importance. PCT has a marked inductive effect on the microsomal enzymes in the liver in vertebrates and may cause liver-damage--including tumours. Disturbance of the hormonal--and immunological--systems have also been reported. The most important ecological hazard of PCT--as well as PCB--is the possible disturbance of the reproduction system of the organisms. Many countries do not regulate the use of PCT. In some countries the use of PCT is regulated to closed systems, but the expansion of usage is under consideration in the EEC.


Vital signs fluctuations and their relationship with pain in the brain-injured adult critically ill - A repeated-measures descriptive-correlational study.
To evaluate the use of vital signs for pain detection in brain-injured patients in the intensive care unit. A repeated-measures descriptive-correlational study. Two neurological intensive care units in Montréal, Canada. A total of 101 brain-injured patients were included. This study examined the fluctuations in systolic and diastolic blood pressure, heart and respiratory rates, and oxygen saturation in brain-injured critically ill patients before, during, and 15 minutes after turning and soft touch using a data collection computer. When possible, patients' pain self-reports were obtained using a 0-10 Faces Pain Thermometer. The heart and respiratory rates were higher during turning than soft touch and higher during the procedure compared to prior (p < 0.05), but their fluctuation was modest. The systolic blood pressure increased during both turning and soft touch by 2 mmHg, but was 26.6 mmHg higher for those who reported pain versus no pain (Mann-Whitney = 25.00, p = 0.008, n = 28). A moderate correlation was observed between the systolic blood pressure (Spearman's rho = 0.617, p = 0.004, n = 24) and self-reported pain intensity during turning. No significant effects were observed for diastolic blood pressure and oxygen saturation. Only increases in systolic blood pressure were positively associated with pain in this sample and replication studies with larger samples is needed.


Congenital malformation of the feet with low body height. A new syndrome, caused by an autosomal dominant gene.
Among 75 members of a Danish family, 12 were found with a syndrome not previously described. Clinically, the syndrome consists of low body height and rigid flat feet, with weight-bearing pain in the feet. Radiologically, the deformation of the feet is a medial synostosis between the talus and the calcaneus combined with ankle joint dysplasia. The cause of the syndrome is most probably an autosomal dominant gene with complete penetrance. No linkage was found of the gene to 18 marker genes.


Systematic review with meta-analysis: comparison between therapeutic regimens for paediatric chronic hepatitis C.
To decide when and how to treat children with chronic hepatitis C is an ongoing debate. To compare the outcomes of therapy for children with chronic hepatitis C. An electronic database assessed clinical trials with sustained virological response rates specified by genotype. The data were extracted according to the therapeutic regimen; interferonα±ribavirin and pegylated interferonα±ribavirin. The search sourced 23 peer-reviewed articles which enrolled 934 cases, aged 2-19 years. Sustained virological response rates were significantly higher with the addition of ribavirin to either interferonα or pegylated nterferonα vs. their monotherapies for genotypes 1,2&3 with crude and weighted estimates. The weighted estimate indicated higher sustained virological response rates for those treated with pegylated interferonα+ribavirin vs. interferonα+ribavirin for genotype 1 (50% vs. 40%) and genotypes 2&3 (90% vs. 84%), (odds ratio 1.5, 95% confidence interval 1.2-1.8, and 1.8, 1.2-2.9 respectively). Cases with genotype 4 treated with pegylated interferonα+ribavirin had a lower sustained virological response (41%) vs. genotype 1 (1.4, 1.2-1.8), and vs. genotypes 2&3 (13.5, 10.3-17.9). Some adverse events were significantly higher among cases treated with pegylated interferonα+ribavirin vs. interferonα+ribavirin. Despite the superiority of pegylated interferonα+ribavirin to interferonα+ribavirin for the treatment of chronic hepatitis C among children, the significant higher adverse events along with the modest outcome for genotypes 1&4 render that regimen a suboptimal therapy. These data indicated the need for the future comparison with clinical trials of direct anti-viral drugs for children with chronic hepatitis C.


Facilitating intracorporeal colorectal anastomoses.
An experimental study was undertaken to evaluate whether a previously described technique for laparoscopic sigmoid resection with intracorporeal resection-anastomosis and specimen removal via a suprapubic incision could be facilitated and applied to the rectum. Ten domestic pigs (median weight 41 kg) underwent low anterior resection of the rectum, which was transected with an articulating endoscopic stapler. Pursestring sutures were fashioned intracorporeally with a laparoscopic pursestring clamp. The anvil of a circular stapler was inserted through a 33 mm port into the colon and pursestring tied intracorporeally. A circular gun with a spike fixed to its shaft was introduced per anum and a double-stapled anastomosis performed. Complete doughnuts were obtained in all cases and anastomoses were all methylene blue tight. All porcine subjects had an uneventful 5-week postoperative course. The median anastomotic level from the anal verge was 5.2 cm. Histology of colorectal anastomoses revealed healing mucosa. The use of articulating endoscopic stapler, laparoscopic pursestring clamp, and circular stapler with a spike fixed to its shaft seems to facilitate a previously described intracorporeal approach to sigmoid resection which was safely applied to the rectum in a porcine model.


Choristoma of the soft palate.
A 2-month-old girl presented with a history of intermittent cyanosis and dyspnea after feeding. This was found to be due to a 2 cm long polypoid lesion attached to her soft palate. This was removed and histologic examination showed it to be choristoma. Three years later she remains well with no evidence of recurrence.


Prevalence of hypertension and associated factors in female prison correctional officers in a national sample in Brazil.
To estimate hypertension prevalence and associated factors among female correctional officers (FCO) in female Brazilian prisons. Cross-sectional, analytical study conducted in 15 female prisons in all five Brazilian regions between January 2014 and December 2015. The study population consisted of correctional officers with at least 6 months in the position. The sampling included 40% of FCO present in the prison during data collection, yielding 295 FCOs. Data were collected via Audio Computer-Assisted Self-Interview. A physical examination of participants was conducted including blood pressure, weight, and waist and hip circumference. The Odds Ratio and confidence intervals for independent factors were estimated. Hypertension prevalence in correctional officers was 37.9%, (95% CI 32.1-44.0). Hypertension was associated with obesity (95% CI = 1.884-9.947), cardiovascular disease (95% CI = 3.348-16.724), and participation in the specific training course for the relevant position (95% CI = 1.413-9.564). While findings, except for the last factor, are not novel, this is the first such study conducted in Brazil. Hypertension prevalence among this pool of all female correctional officers is higher than in the average population, and FCOs associate this with the prison environment. Current training does not appear to address this problem. Especially since prison populations are growing in Brazil, this problem needs to be addressed for the health of the FCOs and the prisoners in their care.


A precipitin for human serum proteins as released under stress by a marine invertebrate, the marsh snail, Littorina irrorata.
A substance released into the environment by stressed marsh snails, Littorina irrorata, precipitates with the beta globulin and albumin fractions of human serum proteins. Other diverse invertebrate species may produce a similar substance. Invertebrate precipitins have not been widely reported, and none like the one described. Some physicochemical and adaptive characteristics of the snail precipitin are presented. This precipitin can be produced in large quantities and has potential application as a diagnostic reagent.


The potential role of RTN3 in monocyte recruitment and atherosclerosis.
The recruitment of monocytes to arterial wall and their transformation into macrophages are generally accepted as important early events in the pathogenesis of atherosclerosis (AS). Our research group found Reticulon3 (RTN3), a member of the reticulon family, may be a candidate pathogenic element in the progress of AS. But it is virtually unknown in which process RTN3 may participate in and regulate the pathogenesis of AS. Here, we hypothesis that RTN3 may participate in the continuous process of circulating monocyte recruitment in AS including: (1) monocyte spreading and adhesion to luminal endothelium; (2) transendothelial migration and may also contribute to the conversion of monocyte to macrophage in subendothelium.


Chitosan/silk fibroin modified nanofibrous patches with mesenchymal stem cells prevent heart remodeling post-myocardial infarction in rats.
Poor functional survival of the engrafted stem cells limits the therapeutic efficacy of stem-cell-based therapy for myocardial infarction (MI). Cardiac patch-based system for cardiac repair has emerged as a potential regenerative strategy for MI. This study aimed to design a cardiac patch to improve the retention of the engrafted stem cells and provide mechanical scaffold for preventing the ventricular remodeling post-MI. The patches were fabricated with electrospinning cellulose nanofibers modified with chitosan/silk fibroin (CS/SF) multilayers via layer-by-layer (LBL) coating technology. The patches engineered with adipose tissue-derived mesenchymal stem cells (AD-MSCs) (cell nano-patch) were adhered to the epicardium of the infarcted region in rat hearts. Bioluminescence imaging (BLI) revealed higher cell viability in the cell nano-patch group compared with the intra-myocardial injection group. Echocardiography demonstrated less ventricular remodeling in cell nano-patch group, with a decrease in the left ventricular end-diastolic volume and left ventricular end-systolic volume compared with the control group. Additionally, left ventricular ejection fraction and fractional shortening were elevated after cell nano-patch treatment compared with the control group. Histopathological staining demonstrated that cardiac fibrosis and apoptosis were attenuated, while local neovascularization was promoted in the cell nano-patch group. Western blot analysis illustrated that the expression of biomarkers for myocardial fibrosis (TGF-β1, P-smad3 and Smad3) and ventricular remodeling (BNP, β-MHC: α-MHC ratio) were decreased in cell nano patch-treated hearts. This study suggests that CS/SF-modified nanofibrous patches promote the functional survival of engrafted AD-MSCs and restrain ventricular remodeling post-MI through attenuating myocardial fibrosis. STATEMENT OF SIGNIFICANCE: First, the nanofibrous patches fabricated from the electrospun cellulose nanofibers could mimic the natural extracellular matrix (ECM) of hearts to improve the microenvironment post-MI and provide three dimensional (3D) scaffolds for the engrafted AD-MSCs. Second, CS and SF which have exhibited excellent properties in previous tissue engineering research, such as nontoxicity, biodegradability, anti-inflammatory, strong hydrophilic nature, high cohesive strength, and intrinsic antibacterial properties further optimized the biocompatibility of the nanofibrous patches via LBL modification. Finally, the study revealed that beneficial microenvironment and biomimetic ECM improve the retention and viability of the engrafted AD-MSCs and the mechanical action of the cell nano-patches for the expanding ventricular post-MI leads to suppression of HF progression by inhibition of ventricular remodeling.


The development of blood protein profiles in extremely preterm infants follows a stereotypic evolution pattern.
Preterm birth is the leading cause of neonatal mortality and morbidity. Early diagnosis and interventions are critical to improving the clinical outcomes of extremely premature infants. Blood protein profiling during the first months of life in preterm infants can shed light on the role of early extrauterine development and provide an increased understanding of maturation after extremely preterm birth and the underlying mechanisms of prematurity-related disorders. We have investigated the blood protein profiles during the first months of life in preterm infants on the role of early extrauterine development. The blood protein levels were analyzed using next generation blood profiling on 1335 serum samples, collected longitudinally at nine time points from birth to full-term from 182 extremely preterm infants. The protein analysis reveals evident predestined serum evolution patterns common for all included infants. The majority of the variations in blood protein expression are associated with the postnatal age of the preterm infants rather than any other factors. There is a uniform protein pattern on postnatal day 1 and after 30 weeks postmenstrual age (PMA), independent of gestational age (GA). However, during the first month of life, GA had a significant impact on protein variability. The unified pattern of protein development for all included infants suggests an age-dependent stereotypic development of blood proteins after birth. This knowledge should be considered in neonatal settings and might alter the clinical approach within neonatology, where PMA is today the most dominant age variable.


Expression, localization, and phosphorylation of Akt1 in benign and malignant thyroid lesions.
The serine/threonine protein kinase Akt is a key molecule in the phosphatidyl inositol 3-kinase pathway that is often overactivated in human cancers. Three Akt isoforms (Akt1, Akt2, Akt3) have been identified in human cells and they show different distribution and have non-redundant functions. The aim of this study was to determine whether the expression, phosphorylation, and localization of Akt1 isoform in human thyroid malignant lesions are different from those in benign lesions. Nuclear and cytoplasmic fractions were isolated from tissue samples and Western blot method was used to detect Akt1 presence in both cellular fractions. Akt1 expression was also assessed by ELISA method. To estimate Akt1 phosphorylation, kinase was immunoprecipitated from cell lysates and tested with anti-phospho-Akt antibodies. The Akt1 expression in majority of thyroid cancer samples was significantly higher than in benign lesions (p < 0.05). Akt1 both in differentiated cancers (follicular and papillary) and benign lesions was localized mainly in cytoplasmic fraction. In two of three anaplastic cancer samples Akt1 was predominantly localized in nucleus. The ratio of phosphorylated Akt1 to total Akt1 was lower in cancers than in non-neoplastic lesions and adenomas. Thus, although Akt1 seems to be overexpressed in thyroid neoplasms, its high phosphorylation is not characteristic for thyroid cancers.


Endothelialization and patency of RGD-functionalized vascular grafts in a rabbit carotid artery model.
To address the growing demand of small-diameter vascular grafts for cardiovascular disease, it is necessary to develop substitutes with bio-functionalities, such as anticoagulation, rapid endothelialization, and smooth muscle regeneration. In this study, the small-diameter tubular grafts (2.2 mm) were fabricated by electrospinning of biodegradable polymer polycaprolactone (PCL) followed by functional surface coating with an arginine-glycine-aspartic acid (RGD)-containing molecule. The healing characteristics of the grafts were evaluated by implanting them in rabbit carotid arteries for 2 and 4 weeks. Results showed that at both time points, all 10 of the RGD-modified PCL grafts (PCL-RGD) were patent, whereas 4 of the 10 non-modified PCL grafts were occluded due to thrombus formation. Scanning electron microscopy (SEM) data showed abundant platelets adhering on the surface of the midportion of the PCL grafts. In contrast, only few platelets were observed on the PCL-RGD surface, suggesting that RGD modification significantly improved the hemocompatibility of the PCL grafts. Histological analysis demonstrated enhanced cell infiltration and homogeneous distribution within the PCL-RGD grafts in comparison with the PCL grafts. Furthermore, immunofluorescence staining also showed a 3-fold increase of endothelial coverage of the PCL-RGD grafts than that of PCL grafts at those two time points. After 4-week implantation, 65.3 ± 7.6% of the surface area of the PCL-RGD grafts was covered by smooth muscle cell layer, which is almost 23% more than that on the PCL grafts. The present study indicates that RGD-modified PCL grafts exhibit an improved remodeling and integration capability in revascularization.


Risk Factors for Cardiovascular Disease in Obese Children.
To study the prevalence of cardiovascular risk factors in pediatric obesity. 50 obese children (age 5-17y) and 50 apparently healthy non-obese children (body mass index of over 95th percentile and between 5th to 95th percentiles, respectively) using Centre for Disease Control growth charts were included. Fasting blood sugar, lipid profile, insulin, homeostasis model assessment of insulin resistance, uric acid, fibrinogen, lipoprotein (a), homocysteine, malondialdehyde, ferric reducing ability of plasma and nitric oxide were measured. Insulin, insulin resistance, triglycerides, uric acid, fibrinogen, malondialdehyde, ferric reducing ability of plasma and nitric oxide were significantly higher (P <0.001) in obese children. Body mass index showed significant positive correlation with insulin r=0.519, P<0.001; insulin resistance r =0.479, P<0.001; uric acid r= 0.289, P=0.005; fibrinogen r=0.461, P<0.001; and nitric oxide r=0.235, P=0.012. Pediatric obesity is associated with dyslipidemia, oxidative stress, insulin resistance and endothelial dysfunction, which are cardiovascular risk factors and components of metabolic syndrome. These children must be targeted for lifestyle and dietary modification.


Prevalence and spectrum of residual symptoms in Lyme neuroborreliosis after pharmacological treatment: a systematic review.
Controversy exists about residual symptoms after pharmacological treatment of Lyme neuroborreliosis. Reports of disabling long-term sequels lead to concerns in patients and health care providers. We systematically reviewed the available evidence from studies reporting treatment of Lyme neuroborreliosis to assess the prevalence and spectrum of residual symptoms after treatment. A literature search was performed in three databases and three clinical trial registers to find eligible studies reporting on residual symptoms in patients after pharmacological treatment of LNB. Diagnosis must have been performed according to consensus-derived case definitions. No restrictions regarding study design or language were set. Symptom prevalence was pooled using a random-effects model. Forty-four eligible clinical trials and studies were found: 8 RCTs, 17 cohort studies, 2 case-control studies, and 17 case series. The follow-up period in the eligible studies ranged from 7 days to 20 years. The weighted mean proportion of residual symptoms was 28 % (95 % CI 23-34 %, n = 34 studies) for the latest reported time point. Prevalence of residual symptoms was statistically significantly higher in studies using the "possible" case definition (p = 0.0048). Cranial neuropathy, pain, paresis, cognitive disturbances, headache, and fatigue were statistically significantly lower in studies using the "probable/definite" case definition. LNB patients may experience residual symptoms after treatment with a prevalence of approximately 28 %. The prevalence and spectrum of residual symptoms differ according to the applied case definition. Symptoms like fatigue are not reported in studies using the "probable/definite" case definition. As the "possible" case definition is more unspecific, patients with other conditions may be included. Reports of debilitating fatigue and cognitive impairment after LNB, a "post-Lyme syndrome", could therefore be an artifact of unspecific case definitions in single studies.


Chest pain secondary to drug use treated in hospital emergency departments in Spain.
To determine the characteristics of patients with chest pain (CP) associated with recent drug use. Study of cases from the REUrHE registry attended in the emergency department of 11 Spanish hospitals for CP following recreational drug use. CP accounted for 8.97% of attendances (males 82.9%, p<0.001). Cocaine was present in 70% of cases, followed by cannabis (35.7%) and amphetamines and derivatives (21.4%). The most frequent initial symptoms were: palpitations (45.5%, p<0.001), anxiety (42.5%, p<0.001), hypertension (13.6%, p<0.001) and arrhythmias (5.9%, p<0.001). Patients with TD received more treatment (81.9% vs 74.1%; p<0.001), although they were admitted less (7.6%, p=0.0), with no differences in terms of CPR manoeuvres, sedation, intubation, or admission to intensive care (1.9%). In CP following acute drug intoxication, cocaine use predominates, although cases of cannabis use are increasing.


Transcriptome analysis of changes in M. aeruginosa growth and microcystin production under low concentrations of ethinyl estradiol.
Ethinyl estradiol (EE2) is a synthetic environmental estrogen with considerable estrogenic activity. It has been found to consequently pose a significant threat to the aquatic ecosystem. Harmful algal blooms are a major aquatic ecological issue. However, the relationship between EE2 and cyanobacterial bloom is mainly unknown. In this study, the physiological and molecular responses of Microcystis aeruginosa to EE2 exposure were investigated. A low level of EE2 (0.02 μg/L) significantly enhanced the growth of algal cells (P < 0.05), whereas higher concentrations of EE2 (0.2-200 μg/L) inhibited it. EE2 at doses ranging from 0.02 to 200 μg/L promoted the production of microcystins (MCs), with genes mcyABD playing a key role in the regulation of MC synthesis. The alterations of chlorophyll-a, carotenoid, and phycocyanin contents caused by EE2 showed the same trend as cell growth. At the molecular level, 200 μg/L EE2 significantly down-regulated genes in photosynthetic pigment synthesis, light harvesting, electron transfer, NADPH, and ATP generation. High concentrations of EE2 caused oxidative damage to algal cells on the 4th d. After 12d exposure, although there was no significant change in superoxide dismutase (SOD) content and no damage observed in membrane lipids, genes related to SOD and glutathione were changed. In addition, due to the down-regulation of pckA, PK, gltA, nrtA, pstS, etc., carbon fixation, glycolysis, TCA cycle, nitrogen and phosphorus metabolism were hindered by EE2 (200 μg/L). Gene fabG in fatty acid biosynthesis was significantly up-regulated, promoting energy storage in cells. These findings provide important clues to elucidate the effects and mechanisms of cyanobacterial blooms triggered by EE2 and help to effectively prevent and control cyanobacterial blooms.


An application of beam theory to determine the stress and deformation of long bones.
We present a generalized beam theory in which deformation and load are determined simultaneously, in order to analyze statically indeterminant problems involving long bones. We regard a long bone as a beam curved in three dimensions for which the cross-sectional properties vary continuously along its length. The theory is used to determine the force, moment, deflection and twist along the fifth metatarsal when it is subjected to both a pointwise and a distributed load.


A hundred-year retrospective on cryptosporidiosis.
Tyzzer discovered the genus Cryptosporidium a century ago, and for almost 70 years cryptosporidiosis was regarded as an infrequent and insignificant infection that occurred in the intestines of vertebrates and caused little or no disease. Its association with gastrointestinal illness in humans and animals was recognized only in the early 1980s. Over the next 25 years, information was generated on the disease's epidemiology, biology, cultivation, taxonomy and development of molecular tools. Milestones include: (i) recognition in 1980 of cryptosporidiosis as an acute enteric disease; (ii) its emergence as a chronic opportunistic infection that complicates AIDS; (iii) acknowledgement of impact on the water industry once it was shown to be waterborne; and (iv) study of Cryptosporidium genomics.


The correlation between brain gray matter volume and empathizing and systemizing quotients in healthy children.
The abilities to empathize and to systemize, two fundamental dimensions of cognitive style, are characterized by apparent individual differences. These abilities are typically measured using an empathizing quotient (EQ) and a systemizing quotient (SQ) questionnaire, respectively. The purpose of this study was to reveal any correlations between EQ and SQ scores and regional gray matter volumes in healthy children by applying voxel-based morphometry to magnetic resonance images. We collected MRIs of brain structure and administered children's versions of the EQ and SQ questionnaires (EQ-C and SQ-C, respectively) to 261 healthy children aged 5-15 years. Structural MRI data were segmented, normalized, and smoothed using an optimized voxel-based morphometric analysis. Next, we analyzed the correlation between regional gray matter volume and EQ-C and SQ-C scores adjusting for age, sex, and intracranial volume. The EQ-C scores showed significant positive correlations with the regional gray matter volumes of the left fronto-opercular and superior temporal cortices, including the precentral gyrus, the inferior frontal gyrus, the superior temporal gyrus, and the insula, which are functionally related to empathic processing. Additionally, SQ-C scores showed a significant negative correlation with the regional gray matter volume of the left posterior parietal cortex, which is functionally involved in selective attention processing. Our findings suggest that individual differences in cognitive style pertaining to empathizing or systemizing abilities could be explained by differences in the volume of brain structures that are functionally relevant to empathizing and systemizing.


Herpes simplex virus type-1 amplicon vectors for vaccine generation in acute lymphoblastic leukemia.
For leukemia vaccine generation, high-efficiency gene transfer is required to express immunomodulatory molecules that stimulate potent antileukemic immune responses. In this context, herpes simplex virus type-1 (HSV-1)-derived vectors have proven to be a promising tool for genetic modification of lymphoblastic leukemia cells. Yet, vector-associated viral protein expression might inadvertently modulate vaccine efficacy facilitating both immune evasion and immune stimulation. To explore the issue of immune-stimulation versus immune-suppression in immature lymphoblastic leukemia cells, two types of HSV-1 amplicon vectors, helper virus-dependent and helper virus-free that express the immunomodulatory molecules CD70 and IL-2, were compared with regard to their vector-associated immunomodulatory potential. We first established that lymphoblastic cell lines and primary acute lymphoblastic leukemia (ALL) cells express HSV receptor genes. Lymphoblastic cell lines were transduced with high efficiency, and in primary ALL cells high gene transfer rates of 47+/-15 and 42+/-14% were obtained with helper virus-dependent and -free HSV-1 amplicon vectors, respectively. The efficacy of the two amplicon vectors to induce antineoplastic responses was assessed in a vaccine setting in mice with pre-existing highly malignant lymphoblastic disease. Treatment of mice with vaccine cells transgenically expressing CD70+IL2 significantly suppressed lymphoblastic cell proliferation and improved survival. Of note, when helper virus-dependent HSV-1 amplicon vectors were used for vaccine preparation, the high immunogenic potential of the vector itself, in the absence of transgenic CD70+IL2 expression, seemed to be sufficient to mediate protection comparable to the antineoplastic response achieved by expression of immunomodulatory molecules. Thus for vaccine generation in B lymphoblastic leukemia, the immunogenic potential of HSV-1 helper virus-dependent amplicon vectors does provide additional benefit to the high transduction efficiency of HSV-1-derived vectors.


K-ras gene mutational analysis supports a monoclonal origin of biphasic pleomorphic carcinoma of the lung.
We investigated 27 pleomorphic carcinomas of the lung for exon 1 K-ras gene mutations using polymerase chain reaction-single-strand conformation polymophism analysis and direct sequencing. All pleomorphic carcinomas were biphasic, that is, composed of an adeno-, squamous- or large-cell-carcinomatous component associated with a spindle- and/or giant-cell component. Of 27 cases, six (22%) showed K-ras codon 12 mutations, which is a figure higher than that previously reported on in pure sarcoma-like pleomorphic carcinomas. Five tumors displayed the same mutation in both the epithelial and the sarcomatoid components, whereas in one tumor the mutation was restricted to the epithelial component. All mutations occurred in smokers, and were transversions, including GGT (glycine) to TGT (cysteine) change in two cases, to GCT (alanine) in two and to GTT (valine) in two. No significant relationships were found between the occurrence and type of mutations and patients' survival or any other clinicopathological variable, suggesting that K-ras mutations are early events in the development of these tumors. Our results indicate that most, though not all, biphasic pleomorphic carcinomas of the lung are monoclonal in origin, and that cigarette smoking may have a causative role in the development of K-ras alterations in these tumors, as all mutations are transversions.


The Pro78 residue regulates the capacity of the human immunodeficiency virus type 1 Nef protein to inhibit recycling of major histocompatibility complex class I molecules in an SH3-independent manner.
The Nef protein is a crucial pathogenicity factor of human immunodeficiency virus type 1 (HIV-1) that contains a proline-rich motif consisting of four conserved prolines: Pro69 (P69), P72, P75 and P78. P72 and P75 were shown to bind Src homology domains 3 (SH3) and have been implicated in many biological functions of Nef, including downmodulation of cell-surface major histocompatibility complex class I (MHC-I). P78 is involved together with P69 in positioning of the Nef-SH3 complex and it has been shown to be essential for Nef activity of MHC-I downmodulation. It is shown here that alteration of P78 affects recycling of MHC-I molecules to the cell surface, but does not interfere with SH3 binding. In addition, it is demonstrated that P72 and P75, and thus the SH3-binding capacity, are fully dispensable for Nef activity on MHC-I.


cTnI, BNP and CRP profiling after seizures in patients with drug-resistant epilepsy.
To profile serum levels of high sensitivity Troponin I (hs-cTnI), B-Type Natriuretic Peptide (BNP), and high sensitivity C Reactive Protein (hs-CRP), after epileptic seizures in patients with focal drug-resistant epilepsy, relating the results to the revised SUDEP-7 inventory. We prospectively evaluated patients admitted to our Epilepsy Monitoring Unit. hs-cTnI, BNP, and hs-CRP were measured at admission and after the first seizure. The revised SUDEP-7 Risk Inventory was calculated. The statistical significance level was set at 0.05. Fifty-eight patients were included (53.4 % female). The index seizure was a focal to bilateral tonic-clonic seizure (FBTCS) in 25.9 % of the patients, and 17.5 % had post-ictal generalized EEG suppression (PGES). After the seizure, 25.9 % had a significant (above 50 %) increase in hs-cTnI, 23.3 % in BNP, and 4.3 % in hs-CRP. About 40 % had cardiovascular risk factors (CRF), without known cardiac disease. The elevation of one biomarker did not compel the elevation of another. hs-cTnI increase was associated with FBTCS, PGES, longer seizures, maximal ictal heart rate, and HR change. Increases in BNP were associated with CRF. hs-CRP increase was associated with PGES. We found no significant association between SUDEP-7 and any biomarker increase. Several patients had increases in biomarkers of myocardial necrosis/dysfunction after seizures, without significant association with the SUDEP-7 inventory. Different patterns of biomarkers' elevations point to multifactorial pathophysiologies hypothetically associated with incipient myocardial lesions. A larger cohort with follow-up data could help to clarify the clinical relevance of these findings.


[Nuclear trace microfilter--a test for the filtration of fibrous dust particles from fluids].
Nuclear track microfilters produced in GDR were effective in separation of fibrous dust particles out of fluids. Further use of nuclear track microfilters in the field of research is planned.


Effects of aminoglycoside antibiotics on the coupling of protein and RNA syntheses in Escherichia coli.
The interdependency of protein and RNA syntheses was studied comparatively in bacteria confronted with amino acid starvation or treated separately with various aminoglycoside antibiotics. By contrast with the concomitant inhibition of macromolecular syntheses in cells deprived of an essential amino acid, RNA production was found to continue in drug-treated cells while protein synthesis was arrested. Such uncoupling process was also observed in bacteria subjected simultaneously to amino acid starvation and treatment with certain antibiotics (neomycin, gentamicin, spectinomycin and kasugamycin) but not with others (streptomycin and kanamycin). These results were related to the intracellular concentration of guanosine polyphosphates, ppGpp and pppGpp. They were discussed in terms of interaction of aminoglycosides with ribosomes.


Triphenylphosphonium-conjugated glycol chitosan microspheres for mitochondria-targeted drug delivery.
To develop an efficient vector for mitochondria-targeted drug delivery, we synthesized triphenylphosphonium (TPP)-modified glycol chitosan polymeric microspheres that had a unique chemical structure with both lipophilic phenyl groups and cationic phosphonium. Notably, TPP can easily pass through the phospholipid bilayer of mitochondria, thereby resulting in specific accumulation of a combined drug molecule in the mitochondria due to the membrane potential between TPP and its membrane. Therefore, TPP has been widely used as a mitochondria-targeting moiety. Triphenylphosphonium-glycol chitosan derivatives (GC-TPP and GME-TPP) with two different degrees of substitution (11% and 36%) were prepared by amidation and Michael addition. The chemical structures of GC-TPP and GME-TPP were characterized by 1H nuclear magnetic resonance and Fourier-transform infrared spectroscopy, and their sizes were measured via field emission scanning electron microscopy and dynamic light scattering. Cellular uptake through flow cytometric analysis and confocal microscopy confirmed that both GC-TPP and GME-TPP were well introduced into cells, targeting the mitochondria. In addition, cytotoxicity testing of the most common cell lines, such as HEK293, HeLa, NIH3T3, and HepG2, indicated the absence of polymer toxicity. To evaluate the carrier effectiveness of TPP for drug delivery, doxorubicin (Dox) was used as an anticancer drug. Confocal microscopy images showed that Dox-loaded GME-TPP accumulated inside cells more than Dox-loaded GC-TPP. The anticancer effects of Dox were also determined by MTT assay, apoptosis/necrosis assay, and three-dimensional spheroids. In summary, the results indicate that GC-TPP and GME-TPP microspheres possess great potential as effective drug delivery carriers.


Crystal structure of the solid solution Ba8.35Pb0.65(B3O6)6.
Single crystals of lead barium borate, Ba8.35Pb0.65(B3O6)6, octabarium lead(II) hexa-kis-(triborate), have been obtained by spontaneous nucleation from a high-temperature melt. Its three-dimensional structure is constructed on the basis of a BaO9 polyhedron, a (Pb/Ba)O6 octa-hedron (occupancy ratio Pb:Ba = 0.216:0.784) and a condensed B3O6 ring anion. In the crystal, the planar B3O6 anions are stacked in an alternating fashion with Ba and (Pb/Ba) atoms along [001]. A comparison is made with the structures of related solid solutions in the system Ba/Pb/B/O.


Decline of cardiomyocyte contractile performance and bioenergetic function in socially stressed male rats.
Chronic social stress has been epidemiologically linked to increased risk for cardiovascular disease, yet the underlying pathophysiological mechanisms are still largely elusive. Mitochondrial (dys)function represents a potential intersection point between social stress exposure and (mal)adaptive cardiac responses. In this study, we used a rodent model of social stress to study the extent to which alterations in the cellular mechanical properties of the heart were associated with changes in indexes of mitochondrial function. Male adult rats were exposed to repeated episodes of social defeat stress or left undisturbed (controls). ECG signals were recorded during and after social defeat stress. Twenty-four hours after the last social defeat, cardiomyocytes were isolated for analyses of mechanical properties and intracellular Ca2+ dynamics, mitochondrial respiration, and ATP content. Results indicated that social defeat stress induced potent cardiac sympathetic activation that lasted well beyond stress exposure. Moreover, cardiomyocytes of stressed rats showed poor contractile performance (e.g., slower contraction and relaxation rates) and intracellular Ca2+ derangement (e.g., slower Ca2+ clearing), which were associated with indexes of reduced reserve respiratory capacity and decreased ATP production. In conclusion, this study suggests that repeated social stress provokes impaired cardiomyocyte contractile performance and signs of altered mitochondrial bioenergetics in the rat heart. Future studies are needed to clarify the causal link between cardiac and mitochondrial functional remodeling under conditions of chronic social stress.


Effects of growth hormone and insulin-like growth factor 1 (IGF-1 ) on hepatic IGF-1-mRNA, plasma IGF-1 and nitrogen excretion in gastrectomized rats with liver cirrhosis.
The growth hormone (GH)-insulin-like growth factor 1 (IGF-1) axis is impaired in liver cirrhosis. We determined the effects of GH and IGF-1 treatments in gastrectomized rats with thioacetamide-induced cirrhosis. GH did not increase hepatic IGF-1-mRNA, plasma IGF-1 or the tissue, i.e. gastrocnemius muscle IGF-1 level. IGF-1 administration increased plasma IGF-1 without increasing hepatic IGF-1-mRNA. GH and IGF-1 independently decreased postoperative urinary nitrogen excretion. We conclude that both GH and IGF-1 improve postoperative nitrogen metabolism. Furthermore, GH may exert its anabolic effects directly and/or via actions mediated by IGF-1 production, other than in the liver and in the skeletal muscle, in the setting of cirrhosis.


Addition of obliquely crossed spherocylindrical lenses.
This paper presents a three-step method for the addition of obliquely crossed spherocylinders. Contrary to other methods it does not require algorithms or complicated abstract concepts to secure the consistency of the results.


Oculomotor consequences of beta-adrenoceptor antagonism during sustained near vision.
The effect of a topical non-selective beta-adrenergic antagonist, timolol maleate (0.5%) on the response accommodative convergence/accommodation (AC/A) ratio was monitored during a 16 min near-vision task. A double-blind protocol was adopted between timolol and a saline control for 17 emmetropic subjects. Timolol produced a significant reduction in AC/A during the first 4 min of the task with respect to saline. This reduction was mediated via accommodative convergence and it is proposed that this demonstrates direct involvement of sympathetic innervation to the ciliary muscle during the initial stages of a near-vision task.


Apis mellifera cytoplasmic elongation factor 1 alpha (EF-1 alpha) is closely related to Drosophila melanogaster EF-1 alpha.
Using low stringency hybridisation with a Drosophila melanogaster EF-1 alpha gene fragment we have isolated a genomic DNA clone encoding elongation factor 1 alpha (EF-1 alpha) from Apis mellifera. The hybridising Apis mellifera sequence could be delineated to two small EcoRI fragments that were also revealed by genomic Southern hybridisation. By comparison with the corresponding Drosophila melanogaster data the complete translational reading frame has been deduced. It is interrupted by two intervening sequences of 220 and about 790 nucleotides. Comparison with known eucaryotic EF-1 alpha sequences further confirms that certain amino acid sequences seem to be invariable within the EF-1 alpha protein family.


Lysosome blockade induces divergent metabolic programs in macrophages and tumours for cancer immunotherapy.
Platinum-drugs based chemotherapy in clinic increases the potency of tumor cells to produce M2 macrophages, thus leading to poor anti-metastatic activity and immunosuppression. Lysosome metabolism is critical for cancer cell migration and invasion, but how it promotes antitumor immunity in tumours and macrophages is poorly understood and the underlying mechanisms are elusive. The present study aimed to explore a synergistic strategy to dismantle the immunosuppressive microenvironment of tumours and metallodrugs discovery by using the herent metabolic plasticity. Naphplatin was prepared by coordinating an active alkaline moiety to cisplatin, which can regulate the lysosomal functions. Colorectal carcinoma cells were selected to perform the in vivo biological assays. Blood, tumour and spleen tissues were collected and analyzed by flow cytometry to further explore the relationship between anti-tumour activity and immune cells. Transformations of bone marrow derived macrophage (BMDM) and M2-BMDM to the M1 phenotype was confirmed after treatment with naphplatin. The key mechanisms of lysosome-mediated mucolipin-1(Mcoln1) and mitogen-activated protein kinase (MAPK) activation in M2 macrophage polarization have been unveiled. RNA sequencing (RNA-seq) was used to further explore the key mechanism underlying high-mobility group box 1(HMGB1)-mediated Cathepsin L(CTSL)-lysosome function blockade. We demonstrated that naphplatin induces divergent lysosomal metabolic programs and reprograms macrophages in tumor cells to terminate the vicious tumour-associated macrophages (TAMs)-MDSCs-Treg triangle. Mechanistically, macrophages treated with naphplatin cause lysosome metabolic activation by triggering Ca2+ release via Mcoln1, which induces the activation of p38 and nuclear factor-κB (NF-κB) and finally results in polarizing M2 macrophages. In contrast, HMGB1-mediated lysosome metabolic blockade in cancer cells is strongly linked to antitumor effects by promoting cytoplasmic translocation of HMGB1. This study reveals the crucial strategies of macrophage-based metallodrugs discovery that are able to treat both immunologically "hot" and "cold" cancers. Different from traditional platinum-based antitumour drugs by inhibition of DNAs, we also deliver a strong antitumour strategy by targeting lysosome to induce divergent metabolic programs in macrophages and tumours for cancer immunotherapy.


Carbon nitride nanotubes anchored with Cu(I) triggers peracetic acid activation with visible light for removal of antibiotic contaminants: Probing mechanisms of non-radical pathways and identifying active sites.
The peracetic acid (PAA)-activation process has attracted much attention in wastewater treatment. However, the low electron efficiency at the interface between heterogeneous catalysts and PAA has affected its practical application. For this study, we developed a carbon nitride hollow-nanotube catalysts with dispersed Cu(I) sites (Cu(I)-TCN) for the photocatalytic activation of PAA for antibiotics degradation. The obtained Cu(I)-TCN catalyst demonstrated an enhanced capacity for visible light harvesting along with increased charge transfer rates. Specifically, the developed Cu(I)-TCN/visible light/PAA system was able to completely remove antibiotics within 20 min, with a kinetic constant that was 25 times higher than a Cu(I)-TCN/visible light system, and 83 times higher than Cu(I)-TCN/PAA systems. Scavenging experiment and electron paramagnetic resonance (EPR) indicated that singlet oxygen was dominant reactive specie for sulfisoxazole (SIZ) removal. Besides, electrochemical tests and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy verified that the electron transfer efficiency of PAA activation was promoted due to the formation of inner-sphere interactions between PAA and Cu(I)-TCN, resulting in the quick removal of antibiotics. Further, after exposure to visible light, the Cu(I)-TCN excited photogenerated electrons which supplemented the electrons consumed in the reaction and drove the valence cycle of Cu ions. Overall, this research offered novel insights into the non-radical pathway for heterogeneous visible light-driven advanced oxidation processes and their potential for practical wastewater remediation.


Early ambulation after diagnostic transfemoral catheterisation: a systematic review and meta-analysis.
Femoral arterial puncture is the most common method of vascular access for angiography. Because of possible vascular events, all patients are restricted to strict immobilisation and bed rest for 2-24h, which is accompanied by back pain and discomfort. To assess the effects of the duration of bed rest after transfemoral catheterisation on the prevention of vascular complications and general discomfort, pain, urinary discomfort and patient satisfaction. We searched the Cochrane Library, MEDLINE, SCOPUS, CINAHL, Proquest Dissertations, Open SIGLE, Iranmedex and Irandoc. We included blinded or unblinded randomised controlled trials and quasi-randomised controlled trials that used two different durations of bed rest after angiography before the ambulation was permitted. Two reviewers separately assessed the quality of each study and extracted the data. We present dichotomous outcomes as odds ratios with 95% confidence intervals (CI) and continuous outcomes as mean differences with 95% CI. Twenty studies involving a total of 4019 participants with a mean age of 59.5 years were included. The studies considered periods of bed rest ranging from 2 to 24h, which we compared in three main categories. There were no statistically significant differences between categories in the incidence of bleeding, haematoma, bruising, pseudoaneurysm, thrombus or arteriovenous fistula. Back pain intensity was assessed in four studies. Patients had significantly less back pain after 2-4h bed rest compared to 6h bed rest at 2h (mean difference: -0.70, 95% CI: -1.07, -0.32), 4h (mean difference: -0.60, 95% CI: -0.96, -0.24) and 6h of follow-up (mean difference: -3.77, 95% CI: -4.48, -2.92). One study that assessed urinary discomfort reported less urinary discomfort when bed rest lasted 4h compared to 12-24h (mean difference: -1.48; 95% CI: -2.37, -0.59). In addition, reduced bed rest time may significantly decrease the costs of hospital care. This systematic review suggests that patients can be ambulated after 2-3h following transfemoral catheterisation, and that early ambulation had no significant effect on the incidence of vascular complications and may reduce back pain and urinary discomfort.


Use of statin medications and risk of esophageal adenocarcinoma in persons with Barrett's esophagus.
Persons with Barrett's esophagus experience increased incidence of esophageal adenocarcinoma and may benefit from use of preventives. Studies suggest that statin medications may have chemopreventive properties; we therefore assessed the association between statin use and progression to esophageal adenocarcinoma. In a prospective cohort of 411 persons with Barrett's, Cox regression was used to calculate HRs for nonsteroidal anti-inflammatory drug (NSAID) and statin use accounting for variation in use during follow-up and adjusting for age, sex, and smoking. The HRs for statin use among all participants were 0.59 [95% confidence interval (CI), 0.26-1.33] and 0.68 (95% CI, 0.30-1.54) before and after further adjustment for NSAID use, respectively. Among persons with high-grade dysplasia, the HRs for statin use were 0.31 (95% CI, 0.11-0.86) and 0.41 (95% CI, 0.13-1.26) before and after adding NSAIDs to the model, respectively. While the reduced risk of esophageal adenocarcinoma observed among statin users may be explained by chance, the point estimates are similar in magnitude to those previously reported for NSAID use in this cohort and are unlikely to be confounded by known risk factors. Further study in larger cohorts and meta-analyses of the potential for statins to reduce risk of esophageal adenocarcinoma is warranted.


Quantitative analysis of neural plate thickness and cell density during gastrulation in the chick embryo.
We quantitatively analyzed the developing prospective neural and non-neural ectoderm during chicken gastrulation on semithin transverse sections. At stage PS8 (primitive streak stage 8 of Lopez-Sanchez et al. [C. Lopez-Sanchez, L. Puelles, V. Garcia-Martinez, L. Rodriguez-Gallardo, Morphological and molecular analysis of the early developing chick requires an expanded series of primitive streak stages, J. Morphol. 264 (2005) 105-116.], equivalent to stage HH4), the thickest area of the ectoderm agrees in extent with the fate-mapped neural plate we had reported previously. The thickness of the median ectoderm is constantly higher up to a distance of 250mum from Hensen's node, and thickness decreases along a mediolateral gradient with a further drop at the prospective lateral border of the neural plate. A higher cell density of the developing ectoderm also coincided with the prospective neural plate. We observed that cell death does not play an important role in the spatial definition of the neural plate.


Remembering and knowing: using another's subjective report to make inferences about memory strength and subjective experience.
The Remember-Know paradigm is commonly used to examine experiential states during recognition. In this paradigm, whether a Know response is defined as a high-confidence state of certainty or a low-confidence state based on familiarity varies across researchers, and differences in definitions and instructions have been shown to influence participants' responding. Using a novel approach, in three internet-based questionnaires participants were placed in the role of 'memory expert' and classified others' justifications of recognition decisions. Results demonstrated that participants reliably differentiated between others' memory experiences--both in terms of confidence and other inherent differences in the justifications. Furthermore, under certain conditions, manipulations of confidence were found to shift how items were assigned to subjective experience categories (Remember, Know, Familiar, and Guess). Findings are discussed in relation to the relationship between subjective experience and confidence, and the separation of Know and Familiar response categories within the Remember-Know paradigm.


Effectiveness of acupuncture in the treatment of cyclic mastalgia: a study protocol for a randomized controlled trial.
About 68% of women aged 18-44 years have experienced cyclic mastalgia (CM), which occurs during the luteal phase of the menstrual cycle when elevated hormone levels induce greater breast gland thickness. CM has a moderate-to-severe impact on a woman's quality of life. Prior research has suggested that acupuncture may be beneficial for breast pain relief. In this study, we investigate the effectiveness of manual acupuncture (MA) in the treatment of CM compared with that of sham acupuncture (SA). This is a multicenter, randomized, controlled trial. A total of 108 eligible CM patients will be randomly assigned to either MA (n = 54) or SA (n = 54) group using a 1:1 ratio and a stratified, blocked randomization. Acupuncture will be performed two weeks prior to menstruation and discontinued when menses begins. In both the MA and SA group, participants will be given acupuncture three times per week for 2 weeks per menstrual cycle for three consecutive menstrual cycles, encompassing a total of 18 sessions. The primary outcome will be the change in the average daily Breast Pain Visual Analog Scale (VAS-BP) over the first two weeks of menstruation from baseline to endpoints. The number of nominal days of breast pain (NDBP) two weeks before menstruation, World Health Organization Quality-of-Life Scale-Short Form scores, global patient assessment, breast glandular-section thickness, and breast-duct width three days before menstruation will also be measured as secondary outcomes. This prospective randomized trial will help evaluate the efficacy of acupuncture in treating CM. The results of this study will provide evidence of the therapeutic effectiveness of acupuncture on CM. ClinicalTrials.gov Identifier: NCT05408377 , registered on June 7, 2022.


A corpus-driven standardization framework for encoding clinical problems with HL7 FHIR.
Free-text problem descriptions are brief explanations of patient diagnoses and issues, commonly found in problem lists and other prominent areas of the medical record. These compact representations often express complex and nuanced medical conditions, making their semantics challenging to fully capture and standardize. In this study, we describe a framework for transforming free-text problem descriptions into standardized Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) models. This approach leverages a combination of domain-specific dependency parsers, Bidirectional Encoder Representations from Transformers (BERT) natural language models, and cui2vec Unified Medical Language System (UMLS) concept vectors to align extracted concepts from free-text problem descriptions into structured FHIR models. A neural network classification model is used to classify thirteen relationship types between concepts, facilitating mapping to the FHIR Condition resource. We use data programming, a weak supervision approach, to eliminate the need for a manually annotated training corpus. Shapley values, a mechanism to quantify contribution, are used to interpret the impact of model features. We found that our methods identified the focus concept, or primary clinical concern of the problem description, with an F1 score of 0.95. Relationships from the focus to other modifying concepts were extracted with an F1 score of 0.90. When classifying relationships, our model achieved a 0.89 weighted average F1 score, enabling accurate mapping of attributes into HL7 FHIR models. We also found that the BERT input representation predominantly contributed to the classifier decision as shown by the Shapley values analysis.


Stroma-derived three-dimensional matrices are necessary and sufficient to promote desmoplastic differentiation of normal fibroblasts.
Stromagenesis is a host reaction of connective tissue that, when induced in cancer, produces a progressive and permissive mesenchymal microenvironment, thereby supporting tumor progression. The stromal microenvironment is complex and comprises several cell types, including fibroblasts, the primary producers of the noncellular scaffolds known as extracellular matrices. The events that support tumor progression during stromagenesis are for the most part unknown due to the lack of suitable, physiologically relevant, experimental model systems. In this report, we introduce a novel in vivo-like three-dimensional system derived from tumor-associated fibroblasts at diverse stages of tumor development that mimic the stromagenic features of fibroblasts and their matrices observed in vivo. Harvested primary stromal fibroblasts, obtained from different stages of tumor development, did not retain in vivo stromagenic characteristics when cultured on traditional two-dimensional substrates. However, they were capable of effectively maintaining the tumor-associated stromal characteristics within three-dimensional cultures. In this study, we demonstrate that in vivo-like three-dimensional matrices appear to have the necessary topographical and molecular information sufficient to induce desmoplastic stroma differentiation of normal fibroblasts.


[Monitoring of consciousness with BIS during induction of anesthesia. Which muscle relaxant?].
The BIS-index data show that an opiate as Fentanyl is advisable with associations Cisatracurium/Propofol or Vecuronium/Propofol. It is possible to use in these cases a drip infusion to avoid the risk of awareness during intubation.


The personal digital assistant, a new medical instrument for the exchange of clinical information at the point of care.
Personal digital assistants can provide a portable, integrated platform for point-of-care clinical reference, patient management and data communication. Clinical reference programs allow the user to access information from the Internet and guidelines. Patient management programs allow doctors to access and store clinical information. Wireless technologies have potential for rapid exchange of clinical laboratory results and efficient "electronic patient handovers". Thus, these devices provide the potential for true continuity of care across the healthcare system.


Disability-adjusted life years lost due to ischemic heart disease in mainland Portugal, 2013.
Estimates of the burden of ischemic heart disease (IHD), including geographic differences, should support health policy decisions. We set out to estimate the burden of IHD in mainland Portugal in 2013 by calculating disability-adjusted life years (DALYs) and to compare this burden between five regions. Years of life lost (YLLs) were calculated by multiplying the number of IHD deaths in 2013 (Statistics Portugal) by the life expectancy at the age at which death occurred. Years lived with disability (YLDs) were computed as the number of cases of acute coronary syndrome, stable angina and ischemic heart failure multiplied by an average disability weight. Crude and age-standardized DALYs (direct method, Standard European Population) were calculated for mainland Portugal and for the Northern, Central, Lisbon, Alentejo and Algarve regions. In 2013, 95413 DALYs were lost in mainland Portugal due to IHD. YLLs accounted for 88.3% of the disease burden. Age-standardized DALY rates per 1000 population were higher in men than in women, across the entire country (8.9 in men; 3.4 in women) and within each region, ranging from 7.3 in the Northern and Central regions to 11.8 in the Algarve in men, and from 2.6 in the Northern region to 4.6 in Lisbon in women. Nearly 100000 DALYs were lost to IHD in Portugal, mostly through early mortality. This study enables accurate comparisons with other countries and between regions; however, it highlights the need for population-based studies to obtain specific data on morbidity.


Intracatheter hyperthermia and iridium-192 radiotherapy in the treatment of bile duct carcinoma.
We report a case of a patient with locally advanced bile duct carcinoma treated with 4500 cGy external beam radiotherapy, followed 3 weeks later by intracatheter 915 MHz microwave hyperthermia and radiotherapy delivered through a biliary U-tube placed at the time of surgery. Heating was to 43-45 degrees C for 1 hour followed immediately by intracatheter Iridium-192 seeds to deliver 5000 cGy over a 72 hour period. Prior to treatment, a thermal dosimetry study in phanton was conducted, using the same type of U-tube catheter tubing as in the patient. Orthogonal X rays of the patient's porta hepatis region were used to reconstruct the catheter geometry in the phantom. Proper insertion depth was determined thermographically to obtain maximum heating at the center of the tumor. The maximum SAR was 8.8 watts per kilogram per watt input. During the treatment, the average power applied was 30 W. Six months after therapy, the patient is asymptomatic. Although alkaline phosphatase, SGOT and SGPT have remained elevated, bilirubin has returned to normal and computerized tomographic scans and cholangiograms remain stable. A duodenal ulcer developed after therapy and is healing well with conservative medical management. This case demonstrates that hyperthermia applied through biliary drainage catheters is technically feasible and clinically tolerated. We believe the use of intracatheter hyperthermia in conjunction with external and/or intracatheter radiotherapy in selected patients with unresectable bile duct carcinomas warrants further study.


CADD, AI and ML in drug discovery: A comprehensive review.
Computer-aided drug design (CADD) is an emerging field that has drawn a lot of interest because of its potential to expedite and lower the cost of the drug development process. Drug discovery research is expensive and time-consuming, and it frequently took 10-15 years for a drug to be commercially available. CADD has significantly impacted this area of research. Further, the combination of CADD with Artificial Intelligence (AI), Machine Learning (ML), and Deep Learning (DL) technologies to handle enormous amounts of biological data has reduced the time and cost associated with the drug development process. This review will discuss how CADD, AI, ML, and DL approaches help identify drug candidates and various other steps of the drug discovery process. It will also provide a detailed overview of the different in silico tools used and how these approaches interact.


Effect of pimozide and sulpiride on the release of LH and FSH by pituitary cells in culture.
A culture of dispersed rat anterior pituitary cells was used to test the ability of pimozide and sulpiride to affect the basal gonadotropin release and their effects on the response to Gn-RH. Sulpiride did not alter either the basal or the Gn-RH-induced release of LH, and the lowest dose (500 ng/ml) seemed to potentiate the Gn-RH-induced FSH release. On the other hand, both doses of pimozide (100 ng/ml and 10 microgram/ml) significantly inhibited the release of FSH and LH induced by Gn-RH but did not affect the basal release of the two gonadotropins. From these results it is evident that pimozide, at the doses used, is a powerful inhibitor of the pituitary response to Gn-RH in vitro. Sulpiride on the other hand had no effect on the pituitary response to Gn-RH in vitro, except on FSH release, using the lower dose.


Morphological, physio-biochemical and nutritional status as potential markers for grafting compatibility in Kalamata olive cultivar.
Choosing the most compatible and desirable rootstock for Kalamata olive cultivar is an important decision due to the longevity of the orchard and the difficulty rooting of Kalamata cuttings. Therefore, the goal of this study was to examine the morphological, physio-biochemical, and nutritional status as ppotential markers for grafting compatibility between Kalamata olive cultivar and three olive rootstocks (Coratina, Picual, Manzanillo) during two seasons (2020-2021) as well as follow up physio-bichemical and nutritional status of one-year-old Kalamata plants (2022). The results indicated that, Picual rootstock recorded the highest significant grafting success which was associated with increasing number of leaves, leaf area and SPAD value in Kalamata scions by 22.15%, 36.86% and 14.64% compared to Manzanillo rootstock as mean of both seasons, respectively. While, Manzanillo rootstock recorded the highest significant activity for peroxidase and catalase by 51.41% and 60.1% at grafting union compared to Picual rootstock. Moreover, Picual rootstock for Kalamata scions had the highest acid invertase and sucrose synthase activities by 67.23% and 57.94% compared to Manzanillo rootstock. Furthermore, Picual rootstock recorded the highest significant Gibberellic acid by 52.8% and 18.6% compared to Coratina and Manzanillo rootstocks. Meanwhile, Picual rootstock recorded the lowest significant Abscisic acid by 68.17% and 63.15% as well as the lowest total phenols by 14.36% and 23.47% compared to Coratina and Manzanillo rootstocks. This study sheds light for the importance of choosing the suitable rootstock for Kalamata cultivar. Also, sucrose synthase and acid invertase may have a novel role in determining grafting compatibility in olives. Increasing growth promoters (Gibberellic, Nitrogen) and decreasing both growth inhibitors (Abscisic, phenols) and oxidative enzyme (catalase, peroxidase) required for better graft compatibility.


New developments in sunscreens.
Topical sunscreen application is one of the most important photoprotection tool to prevent sun damaging effects in human skin at the short and long term. Although its efficacy and cosmeticity have significantly improved in recent years, a better understanding of the biological and clinical effects of longer wavelength radiation, such as long ultraviolet A (UVA I) and blue light, has driven scientists and companies to search for effective and safe filters and substances to protect against these newly identified forms of radiation. New technologies have sought to imbue sunscreen with novel properties, such as the reduction of calorific radiation. Cutaneous penetration by sunscreens can also be reduced using hydrogels or nanocrystals that envelop the filters, or by binding filters to nanocarriers such as alginate microparticles, cyclodextrins, and methacrylate polymers. Finally, researchers have looked to nature as a source of healthier products, such as plant products (e.g., mycosporines, scytonemin, and various flavonoids) and even fungal and bacterial melanin, which could potentially be used as substitutes or enhancers of current filters.


Developmental changes of gene expression after spinal cord injury in neonatal opossums.
Changes in gene expression have been measured 24h after injury to mammalian spinal cords that can and cannot regenerate. In opossums there is a critical period of development when regeneration stops being possible: at 9 days postnatal cervical spinal cords regenerate, at 12 days they do not. By the use of marsupial cDNA microarrays, we detected 158 genes that respond differentially to injury at the two ages critical for regeneration. For selected candidates additional measurements were made by real-time PCR and sites of their expression were shown by immunostaining. Candidate genes have been classified so as to select those that promote or prevent regeneration. Up-regulated by injury at 8 days and/or down-regulated by injury at 13 days were genes known to promote growth, such as Mitogen-activated protein kinase kinase 1 or transcription factor TCF7L2. By contrast, at 13 days, up-regulation occurred of inhibitory molecules, including annexins, ephrins, and genes related to apoptosis and neurodegenerative diseases. Certain genes such as calmodulin 1 and NOGO, changed expression similarly in animals that could and could not regenerate without any additional changes in response to injury. These findings confirmed and extended changes of gene expression found in earlier screens on 9 and 12 ay preparations without lesions and provide a comprehensive list of genes that serve as a basis for testing how identified molecules, singly or in combination, promote and prevent central nervous system regeneration.


[Manual medicine and osteopathic methods on the growing spine].
The application of various techniques in manual medicine on infants, toddlers and adolescents enjoys widespread acknowledgement not only in the musculoskeletal field but also beyond that. For a long time, the seminars of the DGMM have been trying to structure the advanced training of doctors and the vocational training of physiotherapists and to adjust it according to the latest clinical and scientific findings (in this subject matter). Considering the controversial debates, this seems particularly necessary and meaningful. This article aims to identify the current state of discussion and the consensus between medical associations but it also means to provide assistance in daily routine.


Searching for the 'Aha Moments': Healthcare Social Workers' Experiences of Hope and Meaning-Making during COVID-19.
While serving as the leading mental health providers in healthcare systems during COVID-19, social workers have faced numerous career-defining moments, both negative and positive; however, limited research highlights how healthcare social workers process these pivotal professional and personal encounters to find hope and meaning. The purpose of this study was to gather a deeper understanding of how healthcare social workers navigated oppressive healthcare systems, social injustice, and their personal and professional caregiving roles to sustain hope, meaning, and purpose during COVID-19. Participants were recruited through healthcare social work professional organizations from October to December 2020. Participants (N = 54) completed an individual interview over Zoom or telephone. The study incorporated feminist phenomenology to understand how the predominantly female (96%) sample sustained hope amidst institutional, societal, and personal despair. Five themes emerged from social workers' responses: withstanding existential dread; reclaiming family time and community; embracing "aha moments"; answering the call to action; and yearning for normalcy while balancing personal risk. Findings from this study highlight how social workers confronted oppressive systems and gendered social roles to find hope and meaning in the care that they provided for their clients, families, and communities.


Mast cells inhibit colorectal cancer development by inducing ER stress through secreting Cystatin C.
Mast cells (MCs) are abundantly distributed in the human intestinal mucosa and submucosa. However, their roles and mechanisms in the development of colorectal cancer (CRC) are still unclear. In the present research, we found that the infiltration density of MCs in CRC tissues was positively correlated with improved patients' prognoses. Moreover, MCs suppressed the growth and induced the apoptosis of CRC cells in vitro and in vivo but had no effect on normal colonic epithelial cells. The present study revealed that MCs specifically induced endoplasmic reticulum stress (ERS) and activated the unfolded protein response (UPR) in CRC cells but not in normal cells, which led to the suppression of CRC development in vivo. Furthermore, we found that the secreted Cystatin C protein was the key factor for the MC-induced ERS in CRC cells. This work is of significance for uncovering the antitumor function of MCs in CRC progression and identifying the potential of CRC to respond to MC-targeted immunotherapy.


Virus-like siRNA construct dynamically responsive to sequential microenvironments for potent RNA interference.
Cytoplasmic transportation of therapeutic nucleic acids is deemed as an onerous task with aim of precise knockdown towards the targeted genes. Pertaining to the programed functionalities of natural virus in circumventing the biological barriers, we tailored multifaceted chemistries into manufacture of synthetic siRNA delivery vehicles in resembling the functionalities of viral vectors to dynamically tackle with a sequential of biological obstacles encountered in the journey of systemic anti-tumor RNAi therapy. Once harnessing ligands with RGD motif for specific internalization into subcellular endosomal compartments of the tumor cells, the architecture of the proposed delivery vehicles was subjected to facile transformation responsive to pH stimuli in acidic endosomal compartments. The external biocompatible PEGylation palisade was consequently detached, unveiling the cytomembrane-lytic cationic components to commit disruptive potencies to the anionic endosomal membranes for translocation of siRNA conjugates into cytosol. Eventually, liberation of active siRNA could be accomplished due to its responsiveness to the strikingly high level of glutathione in cytosol, thereby contributing to potent RNAi. Hence, our elaborated virus-mimicking platform has demonstrated significant anti-tumor efficacy through systemic administration of anti-angiogenic RNAi payloads, which inspired prosperous potentials in a variety of therapeutic applications.


Urinary phthalate metabolites and heart rate variability: A panel study.
Phthalates exposure is linked with cardiovascular disease. Decreased heart rate variability (HRV) is an early indicator of cardiac autonomic imbalance. We conducted a longitudinal panel study in 127 Chinese adults with 3 repeated visits to explore the associations of individual and mixtures of phthalates exposure with HRV. We quantified 10 urinary phthalate metabolites by gas chromatograph-tandem mass spectrometer (GC-MS/MS) and 6 HRV indices by 3-channel digital Holter monitors. Linear mixed-effect (LME) models and Bayesian kernel machine regression (BKMR) models were separately implemented to evaluate the associations. After multivariate adjustments, we found that urinary mono-ethyl phthalate (MEP), mono-iso-butyl phthalate (MiBP), and mono-n-butyl phthalate (MBP) at lag 0 day were inversely associated with low-frequency power (LF) or total power (TP) (all P-FDR <0.05). In mixture analysis, we observed negative overall associations of phthalate mixtures at lag 0 day with LF or TP, and MiBP was the major contributor. Moreover, stratified analysis suggested that the inverse relationships of MiBP at lag 0 day with LF and TP were more prominent in subjects aged >50 years (all Pinteraction < 0.01). Our findings revealed that exposure to individual and mixtures of phthalates, especially MiBP, were related to decreased HRV.


Respiratory cryptosporidiosis in the acquired immune deficiency syndrome. Use of modified cold Kinyoun and Hemacolor stains for rapid diagnoses.
We report three cases of primary intestinal cryptosporidiosis with bilateral interstitial pneumonia. The diagnoses were made using two rapid (one-minute) staining procedures, modified cold Kinyoun's solution and a Hemacolor set, on touch preparations of lung biopsy material, sputum, and stool. Intracellular cryptosporidia oocysts in alveolar macrophages suggest possible hematogenous spread of this agent. Opportunistic cryptosporidiosis should be included in the differential diagnosis of pneumonia in patients with acquired immune deficiency syndrome.


[Physicochemical and toxicologic aspects of partial glycerides as carrier systems for transdermal systems].
Lipid containing carrier systems are increasingly important for an intercellular transport of drugs. Out of the numerous lipids, triglycerides and partial glycerides of medium chain fatty acids have become of particular interest as absorption promoters. Their chemical and physical properties as well as their analysis are described. Being lipids which are endogenous or very similar to those, they are distinguished by a very low oral and dermal toxicity and a good tolerance. Also at mucous membranes no morphological changes occur.


A Comprehensive Initiative to Prevent Falls Among Newborns.
Our hospital experienced seven instances of newborns falling over a 7-month period. Until that time, there had been no reported newborn falls. We formed a committee to study the situation and make recommendations for change. Common factors observed were early morning hours and an exhausted parent, usually the mother, falling asleep while feeding the newborn. The committee developed a policy and procedure addressing falls among newborns, created staff education and tools, and posted signage in mothers' rooms. We also updated crib cards to include information about falls and safe sleep, and we revised newborn admission education for parents with additional information about falls. The incidence of newborns falling has decreased since we implemented these changes.


Synergistic effect of herbal plant extract (Hibiscus sabdariffa) in maintain the antioxidant activity of decaffeinated green tea from various parts of Assam.
In the present study, two extraction methods, hot water extraction and ethyl acetate extraction were used to decaffeinate fresh green tea leaf (Camellia assamica) collected from four parts of Assam, NE-India. Both type of extraction methods have significant effect on the antioxidant activity of decaffeinated green tea. Amongst the four samples, Dhekiajuli sample have highest antioxidant activity and total polyphenol as well as flavonoid contents. During hot water extraction (100 °C for 3 min), in decaffeinated green tea, the antioxidant activity decreases to 996.1 ± 26.12 mM TE/g green tea and 1165 ± 31.25 mM TE/g green tea from 1403.07 ± 70.15 mM TE/g and 1587.1 ± 79.355 mM TE/g green tea as observed for caffeinated green tea by DPPH and FRAP assay respectively. Again more antioxidant activity (ranges from 996.1 ± 15.8 to 1421.3 ± 71.06 mM TE/g) was recorded for ethyl acetate extracts compared to hot water extracts of samples. However, the loss in antioxidant activity, due to decaffeination of green tea in our study was minimize by using herbal plant extract, Hibiscus sabdariffa along with the tea extract which shows a synergistic effect.


Complete Genome Sequence of a Clinical Isolate of Enterobacter asburiae.
We report here the complete genome sequence of Enterobacter asburiae strain ENIPBJ-CG1, isolated from a bone marrow transplant patient. The size of the genome sequence is approximately 4.65 Mb, with a G+C content of 55.76%, and it is predicted to contain 4,790 protein-coding genes.


Microarray analysis of mRNAs: experimental design and data analysis fundamentals.
Microarray technology has made it possible to quantify gene expression of thousands of genes in a single experiment. With the technological advancement, it is now possible to quantify expression of all known genes using a single microarray chip. With this volume of data and the possibility of improper quantification of expression beyond our control, the challenge lies in appropriate experimental design and the data analysis.This chapter describes the different types of experimental design for experiments involving microarray analysis (with their specific advantages and disadvantages). It considers the optimum number of replicates for a particular type of experiment. Additionally, this chapter describes the fundamentals of data analysis and the data analysis pipeline to be followed in most common types of microarray experiment.


Topographic organization and morphology of peripallidal and pallidal cells projecting to the striatum in cats.
Injections of small amounts of horseradish peroxidase (HRP) or HRP coupled with wheat germ agglutinin within the caudate nucleus in adult cats resulted in retrograde labeling of neurons within the globus pallidus and within the fibers of internal capsule near the globus pallidus. These triangular and fusiform neurons, measuring 27-30 micron, project topographically to the striatum. The morphology and the location of some of the labeled neurons in these cases resemble the acetylcholinesterase-positive neurons of the nucleus basalis magnocellularis described by other authors. The findings from this study support the existence of a projection from the globus pallidus and peripallidal region to the striatum in cats.


Feasibility of Laser Doppler Vibrometry as potential diagnostic tool for patients with abdominal aortic aneurysms.
The application of laser measurements in medical applications makes it possible to measure even very small vibrations without contacting the skin surface. In the present work we investigate the use of a scanning vibrometer to measure the mechanical wave of the abdominal wall caused by the heart beat and blood pressure pulse. A Laser Doppler Vibrometer, triggered by cardiac signals, is used to scan points on a grid positioned on the abdomen of human subjects. The proposed procedure is intended for detecting anomalies in the abdominal cavity such as aortic aneurysms. Here, we outline the technical setup used in our preliminary in vivo experiments and present some preliminary results. This feasibility study shows that the proposed measurement procedure allows for measuring the skin motion, that the skin motion measured is related to the heart activity, and that there are indication that the presence of an abdominal aortic aneurysm significantly modifies the relation between blood pressure pulsations and skin motion on the abdomen.