Association between migration and physical activity of school-age children left behind in rural Mexico.
The purpose of this study was to explore in rural communities of Mexico, the association between physical activity (PA) in school-age children and exposure to migration. We measured PA through a questionnaire validated in school-age children and used in Mexican National Surveys. Migration status was measured as the number of years a family member had been in the US, and the amount of remittances that family member had sent to their household in Mexico. We used multivariable linear regression to measure the association between physical activity and migration. School-age children who had a migrant family member spent less time on PA per day, especially recreation activities, compared to school-age children without the migrating influence. Also, children who belonged to a family that received remittances and their migrant relative lived ≥ 5 years in US were less likely to engage in PA. Exposure to migration may predict reduction in PA in school-age children left behind in Mexican rural communities from the State of Morelos. These findings call for PA-tailored interventions that consider household migration characteristics.


Applications of a cannulated extrusion needle during vitreoretinal microsurgery.
A specially designed cannulated extrusion needle facilitates the internal drainage of subretinal fluid during vitreoretinal microsurgery. Case histories demonstrate the use of this instrument in the management of complex retinal detachments including eyes with preretinal and subretinal hemorrhage, proliferative vitreoretinopathy with open peripheral retinal breaks, retinal detachment with giant retinal tear, and combined traction-rhegmatogenous detachments due to diabetic retinopathy. This method of internal drainage appears to have specific advantages over standard techniques by allowing the removal of subretinal hemorrhage, the utilization of pre-existing peripheral breaks for internal drainage, and the complete reattachment of shallow posterior pole retinal detachments to allow laser endophotocoagulation.


Macrospirocyclic oligomers based on carbazole and fluorene.
Monodisperse macrospirocyclic oligomers were prepared using self-condensation of the Friedel-Crafts reaction. Through the C-9s of the central fluorene units of four surrounding oligofluorenes, four carbazole units are connected in a series to form a macrocyclic core. These rodlike oligofluorenes form a rigid three-dimensional structure, affording the resulting macrocyclics a high steric hindrance for close interchain packing.


Minimally invasive implantation and computer navigation for a unicondylar knee system.
Clinical results of unicondylar knee arthroplasty can be improved by combining minimally invasive surgical techniques with computer-assisted navigation, according to results reported in the literature. The surgeons surveyed 23 patients who underwent a minimally invasive procedure and 15 patients who underwent a minimally invasive procedure with the use of computer-assisted navigation. The surgeons performed both minimally invasive surgical implantations using the Accuris unicondylar knee arthroplasty (onlay technique; Smith & Nephew, Memphis, Tenn) and the BrainLAB VectorVision uni-knee-system (Brain LAB, Inc, Westchester, Ill). Reported results showed significant improvement of the mechanical leg axis after a minimally invasive surgical procedure (range: 5.23 degrees-0.77 degrees) and a computer-assisted operation (range: 4.18 degrees-0.54 degrees). No significant change of slope and average angle of the implant in relation to the longitudinal tibial axis was reported. The study attempts to show that computer navigation used in minimally invasive unicondylar knee arthroplasty can improve positioning and axis calibration.


From discovery to the coming generation of histone deacetylase inhibitors.
Trichostatin A (TSA) is a Streptomyces metabolite that causes differentiation of murine erythroleukemia cells as well as specific inhibition of the cell cycle of some lower eukaryotes and mammalian cells. The targeted molecule of TSA has been shown by genetic and biochemical analyses to be histone deacetylases (HDACs). Histone acetylation is a key modification to control transcription, and HDACs are profoundly involved in pathogenesis of cancer through removing acetyl groups from histones and other transcriptional regulators. Trapoxin (TPX) and FK228 (also known as FR901228 and depsipeptide because FK228 = FR901228 = depsipeptide), structurally unrelated microbial metabolites, were also shown to inhibit HDACs. These HDAC inhibitors cause cell cycle arrest, differentiation and/or apoptosis of many tumors, suggesting their usefulness for chemotherapy and differentiation therapy. In addition, HDAC inhibitors play important roles in identifying the specific function of the enzymes. Indeed, we identified tubulin as one of the substrates of HDAC6 by means of differential sensitivity to HDAC inhibitors. Since recent studies have revealed that HDACs are structurally and functionally diverse, it should be important to develop inhibitors specific to individual enzymes as more promising agents for cancer therapy. We have synthesized novel TSA/TPX hybrids, which will serve as a basis for developing enzyme-specific HDAC inhibitors.


Discovery and design of DNA and RNA ligase inhibitors in infectious microorganisms.
BACKGROUND: Members of the nucleotidyltransferase superfamily known as DNA and RNA ligases carry out the enzymatic process of polynucleotide ligation. These guardians of genomic integrity share a three-step ligation mechanism, as well as common core structural elements. Both DNA and RNA ligases have experienced a surge of recent interest as chemotherapeutic targets for the treatment of a range of diseases, including bacterial infection, cancer, and the diseases caused by the protozoan parasites known as trypanosomes. OBJECTIVE: In this review, we will focus on efforts targeting pathogenic microorganisms; specifically, bacterial NAD(+)-dependent DNA ligases, which are promising broad-spectrum antibiotic targets, and ATP-dependent RNA editing ligases from Trypanosoma brucei, the species responsible for the devastating neurodegenerative disease, African sleeping sickness. CONCLUSION: High quality crystal structures of both NAD(+)-dependent DNA ligase and the Trypanosoma brucei RNA editing ligase have facilitated the development of a number of promising leads. For both targets, further progress will require surmounting permeability issues and improving selectivity and affinity.


Aesthetic reconstruction of onco-surgical maxillary defects using free scapular flap with and without CAD/CAM customized osteotomy guide.
Reconstruction of the maxillary defects following tumor ablation remains to be a challenge for surgeons. Virtual surgical planning (VSP), intraoperative cutting guides and stereolithographic models provides the head and neck reconstructive surgeon with powerful tools for complex reconstruction planning. Despite its use in fibular osteocutaneous reconstruction, application to the scapular free flap has not been as widely reported. The aim of this study was to compare aesthetic results and operation time of free scapular flap, with and without computer-aided design and computer-aided manufacturing (CAD/CAM) customized osteotomy guide, for reconstruction of maxillary defects. In this prospective randomized controlled clinical trial study, we randomly assigned 22 patients with maxillary defects who were scheduled to undergo maxillary reconstruction with either free scapular flap with CAD/CAM customized osteotomy guide; study group (n = 11) or free scapular flap without CAD/CAM customized osteotomy guide; control group (n = 11). All patients were followed up for 3 months. The aesthetic outcome, operation and ischemic times were evaluated and compared. Aesthetic outcomes were evaluated objectively by means of differential surface area (sagittal and axial) measurement, which showed improved aesthetic outcome (contour symmetry) in the study group with a mean of (241.39 ± 113.74 mm2), compared to patients in control group with a mean of (358.70 ± 143.99 mm2). There were significant differences between the two groups (P < 0.05). Aesthetic outcomes were also evaluated subjectively by means of visual analogue scale (VAS) and patient's satisfaction score (PSS). The postoperative aesthetic appearance was better in the study group with more patients satisfied than that in control group and there were statistically significant differences (P = 0.039). The mean total operative time was 678.81 min and 777.18 min in the study group and control group respectively (P < 0.05) and the mean ischemia time was 133.18 min and 195.72 min for study group and control group respectively (P < 0.05). The ischemia time and total operative time were shorter in the study group compared to those in the control group and there were no flap losses in both groups. The use of CAD/CAM prefabricated cutting guides facilitates scapular flap molding and placement, minimizes ischemic time and operating time as well as improves aesthetic outcomes. Trial registration This trial was registered at ClinicalTrials.gov. NCT03757286. Registration date: 28/11/2018.


Is autophagy rather than apoptosis the regression driver in imatinib-treated gastrointestinal stromal tumors?
Although apoptosis (programmed cell death type I) is more frequently reported in the literature in imatinib-treated gastrointestinal stromal tumor (GIST) cell lines,morphological features consistent with autophagic changes aremore often encountered in surgical specimens of treated patients. Autophagy (programmed cell death type II) is highly regulated by a tumor-suppressor mechanism that mainly involves the genes beclin1, PI3KIII, and bcl2. Being our material not suitable for electron microscopy analysis (not paraformaldehyde-glutaraldehyde-fixed), we evaluated the morphological, biochemical, and immunophenotypical profiles expected to be related to autophagy and apoptosis in a series of surgically resected samples taken from 11 imatinib-treated patients with molecularly characterized GISTs. The samples were examined for imatinib-induced morphological changes, the presence/interactions of the autophagic-related proteins (beclin1, PI3KIII, bcl2, and LC3-II) and the presence of apoptosis-related proteins (caspase 3, caspase 7, and lamin A/C) by means ofWestern blot analysis and coimmunoprecipitation, complemented by immunohistochemistry. We also studied samples of two untreated GISTs used as controls. Sampling areas with different residual cellularity scores fromboth the imatinib-treated and untreated patients showed biochemical and immunohistochemical evidence of high levels of proautophagy beclin1/PI3KIII and low levels of antiautophagy beclin1/bcl2 complexes, together with the presence of LC3-II detected by Western blot analysis, thus supporting the presence of autophagy. There was no expression of cleaved/activated caspase 3 or 7 or cleaved lamin A/C. Our descriptive results support the idea that GISTs activate autophagy rather than apoptosis in response to imatinib treatment and that their molecular makeup includes fingerprints of autophagy.


Racial and geographic issues in gastroesophageal reflux disease.
Gastroesophageal reflux disease (GERD) is a common chronic disorder that is associated with a huge economic burden in the western countries and significantly decreased quality of life. This review focuses on the various multicultural issues in the epidemiology, pathophysiology, diagnosis, and treatment of GERD. The prevalence of GERD appears to be highest in North America and Europe, whereas epidemiologic data from the Indian subcontinent, Africa, South America, and the Middle East are sparse. A limited number of studies have elucidated ethnic differences in GERD in multiracial populations. African Americans and Asians appear to be at a lower risk for the development of complicated GERD including Barrett's esophagus (BE). Whether the pathophysiology of GERD differs among different populations remains to be answered satisfactorily. It appears that most of the factors involved in the pathogenesis of GERD, as described in western populations, are present in Asians but at a lower scale. The current recommendations for the management of GERD by the American College of Gastroenterology may not meet the need for different ethnic groups or for different geographic regions. Recognition of language barriers in understanding the common terms used to describe reflux symptoms should be borne in mind while treating GERD patients with different ethnic backgrounds. In addition, a universally accepted definition for treatment success in GERD patients is lacking. Given the negative impact on health-related quality of life, significant cost ramifications, and increased risk for BE and esophageal adenocarcinoma, the study of multicultural issues in GERD should be considered.


In vivo imaging of transplanted hepatocytes with a 1.5-T clinical MRI system--initial experience in mice.
The feasibility of in vitro mature mouse hepatocyte labeling with a novel iron oxide particle was assessed and the ability of 1.5-T magnetic resonance imaging (MRI) to track labeled mouse hepatocytes in syngenic recipient livers following intraportal cell transplantation was tested. Mouse hepatocytes were incubated with anionic iron oxide nanoparticles at various iron concentrations. Cell viability was assessed and iron oxide particle uptake quantified. Labeled hepatocytes were intraportally injected into 20 mice, while unlabeled hepatocytes were injected into two mice. Liver T2 values, spleen-to-muscle relative signal intensity (RI( spleen/muscle )), and liver-to-muscle relative signal intensity (RI( liver/muscle )) on gradient-echo T2-weighted imaging after injection of either labeled or unlabeled hepatocytes were compared with an ANOVA test followed by Fisher's a posteriori PLSD test. Livers, spleens and lungs were collected for histological analysis. Iron oxide particle uptake was saturable with a maximum iron content of 20 pg per cell and without viability alteration after 3 days of culture. Following labeled-cell transplantation, recipient livers showed well-defined nodular foci of low signal intensity on MRI--consistent with clusters of labeled hepatocytes on pathological analysis--combined with a significant decrease in both liver T2 values and liver-to-muscle RI( liver/muscle ) (P = 0.01) with minimal T2 values demonstrated 8 days after transplantation. Conventional MRI can demonstrate the presence of transplanted iron-labeled mature hepatocytes in mouse liver.


DNA Oncogenic Virus-Induced Oxidative Stress, Genomic Damage, and Aberrant Epigenetic Alterations.
Approximately 20% of human cancers is attributable to DNA oncogenic viruses such as human papillomavirus (HPV), hepatitis B virus (HBV), and Epstein-Barr virus (EBV). Unrepaired DNA damage is the most common and overlapping feature of these DNA oncogenic viruses and a source of genomic instability and tumour development. Sustained DNA damage results from unceasing production of reactive oxygen species and activation of inflammasome cascades that trigger genomic changes and increased propensity of epigenetic alterations. Accumulation of epigenetic alterations may interfere with genome-wide cellular signalling machineries and promote malignant transformation leading to cancer development. Untangling and understanding the underlying mechanisms that promote these detrimental effects remain the major objectives for ongoing research and hope for effective virus-induced cancer therapy. Here, we review current literature with an emphasis on how DNA damage influences HPV, HVB, and EBV replication and epigenetic alterations that are associated with carcinogenesis.


Time knowledge difficulties following treatment for malignant cerebellar tumors.
In children treated for malignant cerebellar tumors, there are only a few studies investigating temporal skills, despite the role of the cerebellum in time processing being generally acknowledged. Children's time knowledge has been defined as the correct representation and use of familiar time units. The present study compares time knowledge in 38 children treated for malignant cerebellar tumors (mean age 11.6 years) with 105 typically-developing (TD) children. The performances on all time knowledge subtests were significantly lower in the tumor group. The results also confirm a lower mean IQ in the children treated for cerebellar tumors, related to slower processing speed and poorer performance on working memory and non-verbal tasks. However, the lower IQ does not explain the considerable difficulties in the acquisition of time knowledge. These results are discussed in the light of the role of the cerebellum in time processing and in the context of two different models of temporal processing: the internal clock model and the neural network state model.


The effect of time to sentinel lymph node biopsy on cutaneous melanoma survival.
Whether timing of sentinel lymph node biopsy (SLNB) in cutaneous melanoma improves survival is not yet clear. The aim of this study was to investigate if the timing of SLNB influences long-term melanoma mortality. A 10-year retrospective cohort study was conducted on 748 cutaneous melanoma patients who underwent excision of the SLN. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models. After adjusting for sex, age, Breslow thickness, mitotic rate, ulceration, and histologic type, patients who underwent early SLNB (≤30 days) and resulted positive on final pathology had a 3 times decreased risk of melanoma mortality (hazard ratio = .29; 95%confidence interval = .11 to .77) in comparison to patients who underwent delayed SLNB (≥31 days) and resulted positive on final pathology. Our findings suggest that early SLNB (≤30 days) improves melanoma survival.


Pharmacoangiography in experimental tumours. Evaluation of vasoactive drugs.
Pharmacoangiography with four vasoactive drugs was performed in experimental renal and hepatic tumours in rats in order to compare their ability to demonstrate tumour vascularity. Three vasoconstrictors, angiotensin, norepinephrine and vasopressin, and one vasodilator, tolazoline, were tested, vasoconstrictors giving most diagnostic information and the difference in effect among these sometimes being small and probably dose-related. This diagnostic effect is based upon the primitive character of tumour vessels, being unable to react upon a vasoactive stimulus. Angiotensin turned out to be the superior drug which corresponds to clinical experiences of this drug.


Insights into dissociative electron transfer in esterified shikonin semiquinones by in situ ESR/UV-Vis spectroelectrochemistry.
In this work, electrogenerated anion and dianion species from shikonin and its ester derivative isovalerylshikonin were characterized by means of ESR/UV-Vis spectroelectrochemistry. Analysis of the spectra supported the proposal that stepwise dissociative electron transfer (DET) takes place during the second reduction process of the esterified compound. Quantum chemical calculations were performed for validating the occurrence of this mechanistic pathway and for obtaining thermodynamic information on the electron transfer process; ΔG(cleavage)(0) was estimated to be -0.45 eV, considering that the two possible products of the overall reaction scheme are both a quinone and carboxylate anions.


The effect of additional strengthening of hip abductor and lateral rotator muscles in patellofemoral pain syndrome: a randomized controlled pilot study.
To study the effect of additional strengthening of hip abductor and lateral rotator muscles in a strengthening quadriceps exercise rehabilitation programme for patients with the patellofemoral pain syndrome. Randomized controlled pilot trial. Clinical setting with home programme. Fourteen patients with patellofemoral pain syndrome. The subjects were randomly assigned to the intervention group (strengthening of quadriceps plus strengthening of hip abductor and lateral rotator muscles) or to the control group (strengthening of quadriceps). Both groups participated in a six-week home exercise protocol. The perceived pain symptoms, isokinetic eccentric knee extensor, hip abductor and lateral rotator torques and the gluteus medius electromyographic activity were assessed before and after treatment. Parametric and non-parametric tests were used to compare the groups before and after treatment with alpha=0.05. Only the intervention group improved perceived pain symptoms during functional activities (P=0.02-0.04) and also increased their gluteus medius electromyographic activity during isometric voluntary contraction (P=0.03). Eccentric knee extensors torque increased in both groups (P=0.04 and P=0.02). There was no statistically significant difference in the hip muscles torque in either group. Supplementation of strengthening of hip abductor and lateral rotator muscles in a strengthening quadriceps exercise programme provided additional benefits with respect to the perceived pain symptoms during functional activities in patients with patellofemoral pain syndrome after six weeks of treatment.


Transcriptomic profiles reveal differences in zinc metabolism, inflammation, and tight junction proteins in duodenum from cholesterol gallstone subjects.
Cholesterol Gallstone Disease (GSD) is a common multifactorial disorder characterized by crystallization and aggregation of biliary cholesterol in the gallbladder. The global prevalence of GSD is ~10-20% in the adult population but rises to 28% in Chile (17% among men and 30% among women). The small intestine may play a role in GSD pathogenesis, but the molecular mechanisms have not been clarified. Our aim was to identify the role of the small intestine in GSD pathogenesis. Duodenal biopsy samples were obtained from patients with GSD and healthy volunteers. GSD status was defined by abdominal ultrasonography. We performed a transcriptome study in a discovery cohort using Illumina HiSeq. 2500, and qPCR, immunohistochemistry and immunofluorescence were used to validate differentially expressed genes among additional case-control cohorts. 548 differentially expressed genes between GSD and control subjects were identified. Enriched biological processes related to cellular response to zinc, and immune and antimicrobial responses were observed in GSD patients. We validated lower transcript levels of metallothionein, NPC1L1 and tight junction genes and higher transcript levels of genes involved in immune and antimicrobial pathways in GSD patients. Interestingly, serum zinc and phytosterol to cholesterol precursor ratios were lower in GSD patients. A significant association was observed between serum zinc and phytosterol levels. Our results support a model where proximal small intestine plays a key role in GSD pathogenesis. Zinc supplementation, modulation of proximal microbiota and/or intestinal barrier may be novel targets for strategies to prevent GSD.


Beneficial effects of Provinols: cardiovascular system and kidney.
Red wine polyphenols have been reported to exert beneficial effects in preventing cardiovascular diseases but their molecular mechanisms of hemodynamic effects on functional cardiovascular and renal changes were studied much less. The review is focused on in vitro as well as in vivo effects of red wine extract containing polyphenolic compounds (Provinols) on cardiovascular systems and kidney in relation to the molecular and biochemical mechanisms of these compounds. This review provides the evidence that Provinols is able to produce ex vivo endothelium-dependent relaxation as a result of enhanced NO synthesis. Administration of Provinols partially prevents the development of hypertension during NO deficiency and accelerates the decrease of blood pressure in already established hypertension. The effects of Provinols include prevention and/or attenuation of myocardial fibrosis, reduction of aortic wall thickening and improvement of vascular functions. These functional and structural alterations are associated with significant augmentation of NO production, seen as the increase of NO synthase activity and eNOS protein expression. Moreover, it has been documented that Provinols decreased the oxidative stress within the cardiovascular system and kidney.


The use of specialized enteral formulas in pulmonary disease.
The relationship between pulmonary disease and nutrition is significant. Malnutrition and its associated adverse pulmonary effects can directly affect outcomes in the individual with pulmonary disease. The use of nutrition support is common for these patients as a supportive or therapeutic measure. Historical reports of adverse respiratory function associated with high parenteral carbohydrate intakes have led to the controversial use of high-fat enteral products in patients with chronic pulmonary dysfunction. The rationale for using this type of formula is that by providing less carbohydrates, carbon dioxide production will be reduced, respiratory quotient will therefore decrease, and a favorable respiratory outcome will result. In the patient with acute respiratory distress syndrome, an inflammatory state exists in which proinflammatory mediators are produced and affect the course of the disease. An enteral formula with modified lipids designed to modulate eicosanoid production and therefore influence the inflammatory cascade is available. This article reviews the rationale for use of modified enteral formulas in both chronic and acute pulmonary disease, reviews the available studies evaluating the efficacy of these formulas, and provides overall recommendations for the use of specialized enteral formulas in individuals with pulmonary disease.


The impact of family asthma management on biology: a longitudinal investigation of youth with asthma.
This study examined longitudinal associations of asthma management-related beliefs and behaviors with changes in asthma-relevant biological markers in a sample of 43 children with asthma. Children (M age = 12.4, 75% male) and parents were interviewed about asthma management beliefs and behaviors. Asthma outcomes included lung function (FEV(1)%), eosinophil counts, and daily cortisol measured at two time points, 18 months apart. Children with a less sophisticated disease belief (termed the "no symptoms, no asthma" belief) displayed eosinophil counts that increased over time, controlling for baseline levels. Poorer family asthma management was associated with increasing eosinophil counts over time. Poorer child asthma management was associated with cortisol output that declined over time. Further, families who reported poorer collaboration with their physician had children who displayed worsening lung function over time. These findings suggest that interventions aimed at teaching families better asthma management approaches and more accurate disease beliefs may have the potential to alter biological profiles in children with asthma.


Begomovirus populations in single plants are complex and may include both well-adapted and poorly-adapted viruses.
Begomoviruses (single-stranded DNA plant viruses transmitted by whiteflies) are economically important pathogens causing epidemics worldwide. Tomato-infecting begomoviruses emerged in Brazil in the 1990's following the introduction of Bemisia tabaci Middle East-Asia Minor 1. It is believed that these viruses evolved from indigenous viruses infecting non-cultivated hosts. However, tomato-infecting viruses are rarely found in non-cultivated hosts, and vice-versa. It is possible that viral populations in a given host are composed primarily of viruses which are well adapted to this host, but also include a small proportion of poorly adapted viruses. Following transfer to a new host, the composition of the viral population would shift rapidly, with the viruses which are better adapted to the new host becoming predominant. To test this hypothesis, we collected tomato and Sida plants growing next to each other at two locations in 2014 and 2018. Total DNA was extracted from tomato and Sida samples from each location and year and used as a template for high-throughput sequencing. Reads were mapped following a highly stringent set of criteria. For the 2014 samples, >98% of the Sida reads mapped to Sida micrantha mosaic virus (SiMMV), but 0.1% of the reads mapped to tomato severe rugose virus (ToSRV). Conversely, >99% of the tomato reads mapped to ToSRV, with 0.18% mapping to SiMMV. For the 2018 samples, 41% of the Sida reads mapped to three Sida-adapted viruses and 0.1% of the reads mapped to ToSRV, while 99.9% of the tomato reads mapped to ToSRV. These results are consistent with the hypothesis that viral populations in a single plant are composed primarily of the virus that is better adapted to the host but also include a small proportion of viruses that are poorly adapted.


[Somatograms of german newborns (author's transl)].
Birth-weight, length and headcircumference of 4748 German newborns in relation to gestational age are presented. There was found a good agreement to weight and length of Austrian newborns (Hohenauer). The own standard curves lie higher than the most used standards of Lubchenko/U.S.A. from 38 weeks onward. The problem interpreting such a standard as a standard of fetal growth are discussed. It seems reasonable to look at weight, length, and headcircumference together. So it may be possible to perseive discordancy of fetal growth.


Risk Factors of Cholera Transmission in Al Hudaydah, Yemen: Case-Control Study.
Yemen has recently faced the largest cholera outbreak in the world, which started at the end of 2016. By the end of 2017, the cumulative reported cases from all governorates reached 777,229 with 2134 deaths. Al Hudaydah was one of the most strongly affected areas, with 88,741 (18%) cases and 244 (12%) deaths reported. The aim of this study was to determine the risk factors associated with cholera transmission in Al Hudaydah city, Yemen. From December 1, 2017 to January 10, 2018, a total of 104 patients with cholera (57 women and 47 men) who presented at cholera treatment centers in Al Hudaydah city with three or more watery stools in a 24-hour period and with moderate or severe dehydration were identified for inclusion in this study. Each case was matched by age and gender with two controls who were living in the neighboring house. A semistructured questionnaire was used to collect data on behavioral and environmental risk factors such as drinking water from public wells, storing water in containers, consumption of unwashed vegetables or fruits, and sharing a toilet. The median age of the cases and controls was 20 years (range 5-80) and 23 years (range 5-85), respectively. Only 6% of cases and 4% of controls were employed. Multivariate analysis showed that eating unwashed vegetables or fruits (odds ratio [OR] 7.0, 95% CI 1.6-30.6, P=.01), storing water in containers (OR 3.0, 95% CI 1.3-7.3, P=.01), drinking water from a public well (OR 2.5, 95% CI 1.1-5.7, P=.02), and using a public toilet (OR 5.2, 95% CI 1.1-24.4, P=.04) were significantly associated with cholera infection risk. The cholera transmission risk factors in Al Hudaydah city were related to water and sanitation hygiene. Therefore, increasing awareness of the population on the importance of water chlorination, and washing fruits and vegetables through a health education campaign is strongly recommended.


Bcl11b prevents the intrathymic development of innate CD8 T cells in a cell intrinsic manner.
If Bcl11b activity is compromised, CD4(+)CD8(+) double-positive (DP) thymocytes produce a greatly increased fraction of innate CD8(+) single-positive (SP) cells highly producing IFN-γ, which are also increased in mice deficient of genes such as Itk, Id3 and NF-κB1 that affect TCR signaling. Of interest, the increase in the former two is due to the bystander effect of IL-4 that is secreted by promyelocytic leukemia zinc finger-expressing NKT and γδT cells whereas the increase in the latter is cell intrinsic. Bcl11b zinc-finger proteins play key roles in T cell development and T cell-mediated immune response likely through TCR signaling. We examined thymocytes at and after the DP stage in Bcl11b (F/S826G) CD4cre, Bcl11b (F/+) CD4cre and Bcl11b (+/S826G) mice, carrying the allele that substituted serine for glycine at the position of 826. Here we show that Bcl11b impairment leads to an increase in the population of TCRαβ(high)CD44(high)CD122(high) innate CD8SP thymocytes, together with two different developmental abnormalities: impaired positive and negative selection accompanying a reduction in the number of CD8SP cells, and developmental arrest of NKT cells at multiple steps. The innate CD8SP thymocytes express Eomes and secrete IFN-γ after stimulation with PMA and ionomycin, and in this case their increase is not due to a bystander effect of IL-4 but cell intrinsic. Those results indicate that Bcl11b regulates development of different thymocyte subsets at multiple stages and prevents an excess of innate CD8SP thymocytes.


Bacterial biofilms and the pathophysiology of chronic rhinosinusitis.
To review the evidence for the presence of bacterial biofilms in chronic rhinosinusitis (CRS) and mechanisms by which they may contribute to the chronic inflammation characteristic of this disease. Lastly, to provide an overview of the current and potential future treatments for bacterial biofilms in CRS. Advances in the techniques for identifying biofilms have confirmed the presence of bacterial biofilms on the sinonasal mucosa of patients with CRS. The impact on mucosal inflammation of the polymicrobial or multiorganism milieu is not yet well understood. Numerous novel topical therapies for the treatment of bacterial biofilms in CRS have been suggested with some demonstrating clinical efficacy. Blocking of quorum sensing represents a potential future therapy for biofilm treatment in CRS and biofilm infection at large. Biofilms represent an important influence on the pathophysiology of CRS. Further understanding of biofilm interactions and microbial organism behavior will provide us with future treatment modalities for this disease.


Dural-Based Primary Central Nervous System Lymphoma with Bone Invasion.
Primary central nervous system lymphoma (PCNSL) occurs frequently in a deep intraparenchymal location. It rarely occurs in the meninges, and bone invasion is uncommon. A 12-year-old boy was admitted to our hospital with a history of headache and seizures. Magnetic resonance imaging showed a 4-cm-sized dural-based mass with osteolytic bone change. Craniotomy and tumor removal were performed. Operative findings showed a dural-based hard tumor, including necrosis and hemorrhage, and the skull was focally destroyed by tumor cells. The tumor was completely removed. Pathologically, large atypical cells with pleomorphic nuclei and frequent mitoses were found. The tumor cells were immune-positive for CD30, epithelial cell antigen, and anaplastic lymphoma kinase. The final diagnosis was anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALCL). There was no evidence of systemic cancer. The boy underwent chemotherapy following the Non-Hodgkin Lymphoma-Berlin-Frankfurt-Münster protocol. There was no recurrence after a 16-month chemotherapy-off period. ALCL is not a common type of PCNSL, and central nervous system ALCL frequently involves the dura and meninges compared with PCNSL in general. However, osteolytic bone lesions are rarely seen in ALCL. This case thus represents a rare case of dural-based ALCL with bone invasion.


Potential uses of G-quadruplex-forming aptamers.
Guanine quadruplex (G-quadruplex) structures are one of a number of structures which are capable of adopting aptamers. G-rich DNA or RNA has an increased propensity to form quadruplex structures which have unusual biophysical and biological properties. G-rich aptamers which form G-quadruplexes have several advantages over unstructured sequences: G-quadruplexes are non-immunogenic, thermodynamically and chemically stable and they have both higher resistance to various serum nucleases and an enhanced cellular uptake. These advantages have led to a number of synthetic oligonucleotides being studied for their potential use as therapeutic agents for cancer therapy and in the treatment of various other diseases. In addition to their suitability in the fields of medicine and biotechnology, these, highly specified, aptameric G-quadruplexes also have great potential in the further development of nano-devices; e.g. basic components in microarrays, microfluidics, sandwich assays and electrochemical biosensors. This review summarizes the biophysical properties of G-quadruplexes and highlights the importance of the stability and recognition properties of aptamers. Examples of the application of aptamers in medical therapy and in biosensors are also discussed.


Activation of LXRα improves cardiac remodeling induced by pulmonary artery hypertension in rats.
Inflammatory factors regulated by NF-κB play a significant role in PAH and myocardial hypertrophy. LXR activation may inhibit myocardial hypertrophy via suppressing inflammatory pathways; it is unknown whether LXR is also involved in PAH-induced myocardial hypertrophy or remodeling. To further explore the protective effect of LXR in PAH-induced cardiac hypertrophy and remodeling, a PAH model was developed, and T0901317, an agonist of LXR, was used to examine the effect of LXR activation. PAH rats demonstrated obvious cardiac hypertrophy and remodeling in the right ventricle, but significant improvement of cardiac hypertrophy and remodeling was observed in PAH rats treated with T0901317. Through RT-PCR, Western blot and ELISA examination, NF-κB, IL-6, TNF-α, and iNOS were found to be significantly reduced in PAH rats treated with T0901317 compared to PAH rats treated with DMSO. Apoptosis was also significantly reduced in PAH rats treated with T0901317. Thus, LXR activation may inhibit PAH-induced cardiac hypertrophy and remodeling by inhibiting NF-κB-mediated inflammatory pathways.


[Documentation of prehospital emergency care].
The scientific documentation of prehospital emergency care in Sweden is slowly expanding. The first thesis on the value of a mobile coronary care unit was defended in 1982. Since then, at least 106 theses have been defended at 15 educational institutes in Sweden. The theses can be divided into nine different themes, of which acute disease and prognostic factors (n = 30) is the most common, followed in order of frequency by caring, assessment and decision (n = 18), patient and next of kin perspective (n = 14), trauma (n = 1 1), competence, learning, and education (n = 10), care needs, cooperation, and prioritization (n = 10), disaster (n = 7), workers' health and environment (n = 3), and ethics and values (n = 3). The University of Gothenburg had the highest number of theses defended (n = 28), followed by the Karolinska Institute (n = 24) and the University of Umeå (n = 10). The theses were written by 64 nurses, 36 physicians, two public health specialists, one physiotherapist, one priest, one social worker, and one statistician.


First Conclusions on Damage Behaviour of Recycled Carbon Staple Fibre Yarn Using X-ray and Acoustic Emission Techniques.
This paper presents the first results on the characterisation of the damage behaviour of recycled carbon fibre (rCF) rovings manufactured into unidirectionally (UD) reinforced plates. In the first step, the mechanical properties of several material combinations were determined by mechanical tests (tensile, flexural, compression). This proves the usability of the material for load-bearing structures. For example, a tensile modulus of up to 80 GPa and a tensile strength of 800 MPa were measured. Subsequently, the fracture surface was analysed by scanning electron microscopy (SEM) to characterise the fibre-matrix adhesion and to obtain first indications of possible failure mechanisms. Despite the high mechanical properties, poor fibre-matrix adhesion was found for all matrix systems. In situ X-ray microscopy tests were then performed on smaller specimens under predefined load levels as transverse tensile and bending tests. The results provide further predictions of the failure behaviour and can be compared to the previous test results. The three-dimensional scan reconstruction results were used to visualise the failure behaviour of the staple fibres in order to detect fibre pull-out and fibre or inter-fibre failure and to draw initial conclusions about the damage behaviour in comparison to conventional fibre composites. In particular, a benign failure behaviour in the transverse tensile test was demonstrated with this procedure. In addition, first concepts and tests for the integration of AE analysis into the in situ setup of the X-ray microscope are presented.


Pulse-sampling fluorescence lifetime imaging: evaluation of photon economy.
This Letter presents an experimental study comparing the photon rate and photon economy of pulse sampling fluorescence lifetime imaging (PS-FLIm) with the conventional time-correlated single photon counting (TCSPC) technique. We found that PS-FLIm has a significantly higher photon detection rate (200 MHz) compared with TCSPC (2-8 MHz) but lower photon economy (4-5 versus 1-1.3). The main factor contributing to the lower photon economy in PS-FLIm is laser pulse variability. These results demonstrate that PS-FLIm offers 25× faster imaging speed than TCSPC while maintaining room light rejection in clinical settings. This makes PS-FLIm a robust technique for clinical applications.


Trypanosoma cruzi, the Causal Agent of Chagas Disease: Boundaries between Wild and Domestic Cycles in Venezuela.
Trypanosoma cruzi the etiological agent of American Trypanosomiasis or Chagas disease (ChD) is transmitted by triatomines vectors between mammals including man. T. cruzi has existed for circa 150 Ma in the Americas and nearly 10 million people are currently infected. The overlap between wild and domestic ecotopes where T. cruzi circulates is increasing. Host-parasite interactions have been determined by infection patterns in these cycles, all under natural or laboratorial conditions. This mini-review describes specific parasite niches, such as plant communities or biological corridors between domestic and wild landscapes, in order to help identify risk factors for ChD and define the boundaries between wild and domestic transmission cycles, with an emphasis on research undertaken in Venezuela.


Medical and psychosocial experiences of family caregivers with children fed enterally at home.
Pediatric home enteral nutrition (HEN) studies that evaluate the psychosocial aspects of caregiving are limited. Overlooking the psychosocial needs of the caregiver may result in negative outcomes such as lack of adherence to the HEN regimen. This study determined whether caregivers report psychosocial situations more frequent and difficult to manage than medical situations. A questionnaire, which identified 10 psychosocial and 10 medical issues related to pediatric HEN, was mailed to 150 caregivers (37 responded), who rated the statements for frequency and difficulty. Each statement was ranked from most frequent/difficult to least frequent/difficult by mean cross-product score (frequency x difficulty). To indicate overall burden, a medical total composite score (MTCS) and a psychosocial total composite score (PTCS) were calculated by summing the cross-products of the respective problems. Paired t tests compared MTCS to PTCS and also the psychosocial frequency means and difficulty means to the same for the medical problems. Of the top 10 problems, 7 were psychosocial, whereas 3 were medical. Caregivers reported incidences of psychosocial problems more frequently (p < .003) than medical problems, and they had more difficulty (p < .001) with the psychosocial situations than with the medical ones. The PTCS was significantly higher (p < .001) than the MTCS. The psychosocial situations were perceived as causing a greater burden and greater difficulty in coping with everyday life. Health professionals need to understand and address the psychosocial difficulties of the caregiver in order to provide support for the caregiver and promote positive growth and development of the child.


5-Hydroxytryptamine dominates over thromboxane A2 in reducing collateral blood flow by activated platelets.
Intra-aortic infusion of collagen (100 micrograms/kg in 1 min) elicited an extensive platelet activation and transient but marked reductions of blood flow and increases of peripheral vascular resistance, both responses being more pronounced in collaterals than in normal arterial beds in feline hind legs. Blockade of 5-hydroxytryptamine (5-HT) subtype 2 (5-HT2) receptors for 5-HT (ketanserin or ritanserin, 0.63 mg/kg iv, -10 min) or amine depletion (reserpine, 0.1 mg/kg im, -10 days, + parachlorophenylalanine 100 mg/kg sc daily for 3 days), but not cyclooxygenase inhibition (indomethacin, 5 mg/kg iv) or thromboxane (Tx) A2/prostaglandin endoperoxide receptor antagonism (sulotroban, 2.5 mg/kg iv), largely prevented the collagen-induced perfusion defect without interfering substantially with the platelet activation process. TxA2 synthase inhibition, alone (dazoxiben, 5 mg/kg iv) or combined with TxA2-prostaglandin endoperoxide receptor antagonism (ridogrel, 2.5 mg/kg iv), partially reduced the collagen-induced perfusion defect and limited to a similar extent the initial platelet aggregation and release of 5-hydroxyindoles and TxB2 while increasing plasma levels of prostacyclin. These results suggest that platelet-derived 5-HT dominates over TxA2 in reducing blood flow in collateral-dependent tissue of the cat hindlimb.


Clinical Outcomes of Cardiac Shockwave Therapy in Severe Coronary Artery Disease Patients after Coronary Artery Bypass Grafting.
Cardiac shockwave therapy (CSWT) is a noninvasive treatment for patients with refractory angina or myocardial ischemia. This study aims to evaluate the potential beneficial effect and safety of CSWT in patients with severe coronary artery disease (CAD) who have undergone coronary artery bypass grafting (CABG).This was a single-arm prospective cohort study. A total of 30 patients with severe CAD who were not suitable for coronary revascularization and who had undergone CABG were enrolled. All patients received CSWT for nine sessions. Evaluation was performed before and after CSWT, including the Canadian Cardiovascular Society (CCS) classification, New York Heart Association (NYHA) classification, 6-minute walk test (6MWT), Seattle Angina Questionnaire (SAQ) score, nitroglycerin dosage, echocardiography, myocardial perfusion imaging (MPI), and safety parameters. All patients were followed up at both 1 month and 9 months after CSWT.After treatment, CSWT significantly improved CCS classification (P < 0.05), NYHA classification (P < 0.05), nitroglycerin dosage (P < 0.001), and 6MWT (P < 0.05) at 1 month and 9 months after CSWT. SAQ score (P < 0.05) and left ventricular ejection fraction (LVEF; P = 0.037) by echocardiography significantly improved at 1 month after CSWT. Significant decreases in summed stress score (SSS), summed difference score (SDS), ischemic area stress, and ischemic area difference by MPI were observed at 1 month and 9 months after CSWT (P < 0.01). There were no changes in safety parameters before and after CSWT.CSWT may have a beneficial effect on improving myocardial perfusion, clinical symptoms, exertional capacity, and quality of life and is a safe alternative treatment for patients with severe CAD who have undergone CABG.


Endoscopic submucosal dissection for early gastric cancer: are expanded resection criteria safe for Western patients?
Background and study aims Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric cancer (EGC) fulfilling guideline resection criteria or the expanded resection criteria in Asia. It is unclear whether the expanded criteria can be transferred to European patients, and long-term follow-up data are lacking. The aim of this study was to evaluate long-term follow-up data after ESD of EGCs in Europe. Patients and methods Patients with EGC who underwent ESD were included in this single-center study at a German referral center. Patient and lesion characteristics, procedure characteristics, and follow-up data were recorded prospectively. Results A total of 179 patients with 191 EGCs were included over a period of 141 months, with 29.6 % of lesions meeting guideline criteria and 48.6 % meeting expanded criteria. The en bloc resection rate was 98.4 % for guideline criteria and 89.0 % for expanded criteria lesions (P = 0.09), and the R0 resection rate was 90.2 % and 73.6 %, respectively (P = 0.02). The main reason for the expanded criteria was a lesion diameter > 20 mm (81.6 %). perforation 1 %, delayed bleeding 6.3 %, stricture 2.1 %, procedure-related mortality 1.1 %. Local recurrence rate was 0 % for guideline criteria and 4.8 % for expanded criteria lesions (P = 0.06), and the rate of metachronous neoplasia was 15.1 % and 7.1 %, respectively (median follow-up 51 and 56 months, respectively); 92.9 % of metachronous neoplasia were treated curatively with repeat ESD. One patient developed lymph node metastasis after ESD of a submucosal invasive expanded criteria lesion. Long-term-survival was comparable between the two criteria (P = 0.58). No gastric cancer-related death was observed in either group. Conclusions ESD can achieve high rates of long-term curative treatment using the expanded criteria in EGCs in Western countries. We recommend ESD as treatment of choice not only for guideline criteria EGCs but also for intramucosal nonulcerated EGCs regardless of their diameter.


Dietary fatty acids alter the adhesion properties of lymphocytes to extracellular matrix proteins.
Dietary fats have been shown by many investigators to affect immune responses in vitro and in vivo. However, the exact mechanism(s) by which fats or their metabolic derivatives affect immune function is still unknown. In this report we have investigated whether short-term in vitro exposure to fatty acids alters the adhesion of lymphocytes to extracellular matrix proteins. We found remarkably heterogeneous effects with these agents on lymphocyte adhesion; increases and decreases in adhesion were observed depending upon the fatty acid, cell type and extracellular matrix protein used. Alterations in the adhesion potential of lymphocytes could serve as a mechanism for the reported effects of fatty acids on immune function since lymphocytes are dependent upon rapid and reversible adherence events for most of their effector activities.


Novel Rotational Speed Modulation System Used With Venoarterial Extracorporeal Membrane Oxygenation.
Femoral venoarterial extracorporeal membrane oxygenation (VA-ECMO) is widely used to maintain blood flow in patients with cardiogenic shock. However, retrograde blood flow increases left ventricular (LV) afterload during femoral VA-ECMO. Additional support by means of an intraaortic balloon pump (IABP) alleviates LV afterload but is associated with significant adverse events. We previously developed a system for rotational speed modulation in synchrony with the native cardiac cycle, for use with implantable continuous-flow LV assist devices. Here, we aimed to evaluate whether our novel rotation speed modulation system can improve coronary artery flow and reduce LV during femoral VA-ECMO. VA-ECMO was installed by means of right atrial drainage and distal abdominal aortic perfusion in six adult goats. Cardiogenic shock was induced with β-adrenergic antagonist infusion. An IABP was placed in the descending aorta. LV stroke work, LV end-systolic pressure, and coronary arterial flow were evaluated. Data were collected under five conditions (modes): baseline, circuit-clamp (cardiogenic shock), continuous mode (constant rotational speed), counterpulse mode (increasing rotational speed during diastole), and continuous mode with IABP support. LV stroke work and LV end-systolic pressure tended to be lower in the counterpulse mode, indicating decreased LV work load and afterload in this mode. Furthermore, coronary arterial flow tended to be higher in the counterpulse mode. Our system enabled an increase in coronary arterial flow and a decrease in LV work load and afterload during VA-ECMO. The system offers the effects of VA-ECMO and an IABP in a single device.


Effect of Long-Term Aging on Fatigue and Thermal Cracking Performance of Polyphosphoric Acid and Styrene-Butadiene-Styrene-Modified Bio-Blend Bitumen.
Polyphosphoric acid (PPA) and styrene-butadiene-styrene (SBS) were adopted to produce PPA-SBS-modified bio-blend bitumen, which achieved excellent mechanical performance. However, its long-range performance, such as the fatigue and thermal cracking behavior under long-term thermal oxidation, is not well understood. Therefore, a pressure aging vessel (PAV) system was applied to simulate the aging behavior of the bitumen under the action of thermal oxidation. Then, a linear amplitude sweep (LAS) test combined with a viscoelastic continuum damage (VECD) model was applied to investigate the fatigue properties of the bitumen. Moreover, a bending beam rheometer (BBR) test was conducted to evaluate the thermal cracking resistance of the bitumen before and after PAV aging. Meanwhile, an atomic force microscope (AFM) was applied to observe the microscopic topography. The results show that the original compound-modified bitumen can bear more fatigue damage than that of the control bitumen at the failure point, and it also has excellent fatigue resistance at 2.5%, 5%, 7.5%, and 10% applied strain. Moreover, the VECD model can accurately predict the fatigue life of the bitumen under different applied strains. The variation ratio of stiffness modulus for the compound-modified bitumen is below that of the control bitumen after PAV aging, so it shows a better anti-aging performance. Finally, the AFM test shows that PPA and bio-bitumen decrease the heterogeneity of the bitumen, reducing the difference between phases.


Improved insect-proofing: expressing double-stranded RNA in chloroplasts.
RNA interference (RNAi) was discovered almost 20 years ago and has been exploited worldwide to silence genes in plants and animals. A decade later, it was found that transforming plants with an RNAi construct targeting an insect gene could protect the plant against feeding by that insect. Production of double-stranded RNA (dsRNA) in a plant to affect the viability of a herbivorous animal is termed trans-kingdom RNAi (TK-RNAi). Since this pioneering work, there have been many further examples of successful TK-RNAi, but also reports of failed attempts and unrepeatable experiments. Recently, three laboratories have shown that producing dsRNA in a plant's chloroplast, rather than in its cellular cytoplasm, is a very effective way of delivering TK-RNAi. Our review examines this potentially game-changing approach and compares it with other transgenic insect-proofing schemes. © 2018 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Amyloid fibril-nanocellulose interactions and self-assembly.
Amyloid fibrils from inexpensive food proteins and nanocellulose are renewable and biodegradable materials with broad ranging applications, such as water purification, bioplastics and biomaterials. To improve the mechanical properties of hybrid amyloid-nanocellulose materials, their colloidal interactions need to be understood and tuned. A combination of turbidity and zeta potential measurements, rheology and atomic force microscopy point to the importance of electrostatic interactions. These interactions lead to entropy-driven polyelectrolyte complexation for positively charged hen egg white lysozyme (HEWL) amyloids with negatively charged nanocellulose. The complexation increased the elasticity of the amyloid network by cross-linking individual fibrils. Scaling laws suggest different contributions to elasticity depending on nanocellulose morphology: cellulose nanocrystals induce amyloid bundling and network formation, while cellulose nanofibrils contribute to a second network. The contribution of the amyloids to the elasticity of the entire network structure is independent of nanocellulose morphology and agrees with theoretical scaling laws. Finally, strong and almost transparent hybrid amyloid-nanocellulose gels were prepared in a slow self-assembly started from repulsive co-dispersions above the isoelectric point of the amyloids, followed by dialysis to decrease the pH and induce amyloid-nanocellulose attraction and cross-linking. In summary, the gained knowledge on colloidal interactions provides an important basis for the design of functional biohybrid materials based on these two biopolymers.


Prevalence and mechanisms of macrolide resistance among Staphylococcus epidermidis isolates from neutropenic patients in Tunisia.
The prevalence of macrolide-lincosamide-streptogramin (MLS) resistance phenotypes was determined among erythromycin-resistant Staphylococcus epidermidis isolates collected at the Bone Marrow Transplant Centre, Tunisia during 2002. The erm(A), erm(B), erm(C), msrA, mefA and icaA genes were detected by PCR. The vga, vgb and vat genes were amplified from pristinamycin-resistant isolates. The icaA gene was detected in 76.5% of 34 isolates examined in detail. The erm(C) (53%) and erm(A) (32%) genes predominated because of clonal dissemination, followed by msrA (15%). Gene distribution was related to the methicillin resistance pattern. The vga gene was present in combination with erm(A) in three isolates.


Configuration-specific kinetic theory applied to an ideal binary gas mixture.
This paper is the second in a two-part series dealing with the configuration-specific analyses for molecular collision events of hard, spherical molecules at thermal equilibrium. The first paper analyzed a single-component system, and the reader is referred to it for the fundamental concepts. In this paper, the expressions for the configuration-specific collision frequencies and the average line-of-centers collision angles and speeds are derived for an ideal binary gas mixture. The analyses show that the average line-of-centers quantities are all dependent upon the ratio of the masses of the two components, but not upon molecular size. Of course, the configuration-specific collision frequencies do depend on molecular size. The expression for the overall binary collision frequency is a simple sum of the configuration-specific collision frequencies and is identical to the conventional expression.


Mechanisms of cell-mediated myotoxicity. Morphological observations in muscle grafts and in muscle exposed to sensitized spleen cells in vivo.
Fragments of rectus abdominis muscle or diaphragm from AKR or Prince Henry mice were transplanted beneath the skin of the anterior abdominal wall of BALB/C mice and were examined by light and electron microscopy 1-23 days after transplantation. Observations were made on the mode of entry of lymphoid cells into grafts, the nature of the inflammatory cells present in grafts and the interactions between mononuclear cells and regenerating muscle fibres during the rejection phase 7-14 days after transplantation. Lymphoid cells were found to migrate through the endothelium of venules and to enter the space between the basement lamina and the plasma membrane of muscle fibres to make contacts of varying degrees of complexity with the muscle cell membrane. Evidence of penetration of lymphoid cells into muscle fibres (emperipolesis) was found and was usually associated with signs of damage to the muscle fibre. Interactions between mononuclear cells and mature muscle fibres were studied after inoculation of sensitized spleen cells into the musculature of the tongue in mice. Both lymphoid cells and mononuclear phagocytes were found to invade muscle fibres by penetrating the basement lamina. The muscle cell membrane was usually broken down in zones of invasion by mononuclear cells but generally remained intact at sites of invasion by lymphoid cells.


Human hepatocytes are more resistant than rat hepatocytes to anoxia-reoxygenation injury.
We performed this study to determine whether perfused isolated human and rat hepatocytes have different sensitivities to anoxia-reoxygenation injury. Oxygen free radicals were detected by lucigenin-enhanced chemiluminescence. Lipid peroxidation was assessed by measuring malondialdehyde release. Cell injury was evaluated by measuring lactate dehydrogenase release and trypan blue uptake. During the control period, lucigenin-enhanced chemiluminescence, malondialdehyde and lactate dehydrogenase release and trypan blue uptake were similar in rat and human hepatocytes. During 3.5 hr of anoxia, lucigenin-enhanced chemiluminescence decreased to background levels and malondialdehyde release remained constant in both groups. In contrast, lactate dehydrogenase release increased eightfold in rat hepatocytes but only threefold in human hepatocytes. With reoxygenation after 2.5 hr of anoxia, in rat hepatocytes lucigenin-enhanced chemiluminescence increased 13-fold within 15 min and then declined toward control levels. Malondialdehyde release doubled after 1 hr of reoxygenation. The rate of lactate dehydrogenase release increased to a level almost twice that observed in cells kept continuously anoxic. In contrast, with human hepatocytes lucigenin-enhanced chemiluminescence increased only fourfold, whereas malondialdehyde and lactate dehydrogenase releases did not differ significantly from those levels measured in cells perfused continuously under anoxic conditions. At the end of the experiment, the increase in trypan blue uptake was significantly greater with rat hepatocytes than with human hepatocytes. These results demonstrate that (a) during reoxygenation following 2.5 hr of anoxia, isolated human hepatocytes generate fewer oxygen free radical, and lipoperoxides than do rat hepatocytes, and (b) human hepatocytes are more resistant to cell injury during anoxia-reoxygenation than are rat hepatocytes.


A rare cardiac inflammatory myofibroblastic tumor involving aortic valve.
Cardiac inflammatory myofibroblastic tumor (IMT) is an extremely rare benign entity which constitutes a small proportion of primary cardiac tumor. We present a rare case of a 55-year-old symptomatic male patient with a rare cardiac IMT causing left ventricular outflow tract (LVOT) obstruction. The patient received complete tumor resection immediately with uneventful postoperative hospital course. To our best knowledge, cardiac IMT involving aortic valve in older adult causing LVOT obstruction has never been reported before. Additionally, we make a literature review on IMT, focusing on the various clinical presentation of this unpredictable tumor.


Development and Validation of an Individualized Nomogram for Predicting Survival in Patients with Esophageal Carcinoma after Resection.
An accurate estimation of prognosis of the esophageal carcinoma patients after surgery is urgently needed. Clinical nomogram has been developed to quantify risk by incorporating prognostic factors for individual patient. Based on the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2013, a total of 4566 patients were selected. Of those, 3198 patients were assigned to training set to construct the nomogram, which incorporated age, gender, histology, grade, T stage, N stage, nodes examined, radiation and chemotherapy. The calibration curve for probability of survival showed good agreement between prediction by nomogram and actual observation. The C-index of the nomogram was 0.71(95%CI 0.70-0.72), which was statistically higher than the TNM staging system. The results were then validated using bootstrap resampling and a validation set of 1368 patients in the SEER database. Besides, in the esophageal squamous cell carcinoma and esophageal adenocarcinoma subgroups, the nomogram discrimination was superior to the TNM staging system. It is likely that these results would play a supplementary role in the current staging system and help to identify the high risk population after surgery.


Thygeson's superficial punctate keratopathy: A review and case series.
Thygeson's superficial punctate keratitis (TSPK) is a chronic disorder with episodes of exacerbations and remissions which span over years to decades. Typical features of the disease include multiple, grayish white, intraepithelial corneal lesions with minimal or no conjunctival involvement. The exact etiopathogenesis of this entity is unknown. However, it may have a genetic association with HLA-DR3, an antigen proved to be associated with immunogenic responses. Treatment of the disease consists of artificial tears, topical corticosteroids, topical cyclosporine, topical tacrolimus, or usage of soft contact lenses. TSPK should be considered as a diagnosis of exclusion in cases of bilateral superficial punctate keratopathy of long duration. Thirteen patients of TSPK were examined during the last 6 years (2014-2019) at our Institute. Visual acuity was 20/20 to 20/30 in majority cases. All patients required lubricants.


In vitro and in silico analysis of Thymus serpyllum essential oil as bioactivity enhancer of antibacterial and antifungal agents.
Wild thyme (Thymus serpyllum L.) of family Laminaceae is an unexplored perennial medicinal shrub. Aerial part of this plant is traditionally used for the treatment of respiratory and gastrointestinal problems. The current study was designed to evaluate the GC-MS, antimicrobial and synergistic potential of T. serpyllum essential oil (TEO). Chemical characterization of TEO showed the presence of thymol (15.79%), Phenol, 2-(1,1-dimethylethyl) (11.55%), o-Cymene (10.96%) as major phytocompounds. Antimicrobial activity of TEO in terms zone of inhibition (ZOI) varied from 13.66 ± 0.58 mm to 33.66 ± 1.52 mm, while, thymol (10%, v/v) showed ZOI ranged from 15.5 ± 0.5 mm to 26.33 ± 2.08 mm against tested bacterial and fungal species. MIC of TEO was 0.039% to 0.078% against tested bacterial and fungal species, whereas, thymol showed 1.25% to 2.5% MIC against tested bacterial and fungal species. Different combinations of TEO (2MIC to ½MIC) and thymol (2MIC to ½MIC) with antibacterial and antifungal antibiotics (2MIC to ½MIC) were found to increase the efficacy of antibiotics by 4-130 folds against bacterial and fungal pathogens. Molecular docking showed the good binding of thymol with both bacterial and fungal targets. Whereas MD simulation showed the stability of thymol complexed with target proteins over 100 ns time scale. Thymol also fulfills the Lipinski rule and showed characteristics similar to that of drugs. Therefore, it can be concluded from the present study that TEO and its major phytocompound, thymol can act as a bioactivity enhancer of antibacterial and antifungal antibiotics and could be used as a potential candidate to fight against antimicrobial drug resistance.Communicated by Ramaswamy H. Sarma.


Brain metastases: treatment options to improve outcomes.
In recent years, a broader base of treatment options has evolved to improve the outcome for patients with brain metastases. The selection of the most appropriate intervention for the individual patient is dependent on a careful evaluation of the extent of intracranial tumour, as well as an understanding of patient and tumour characteristics that are important determinants of prognosis. Recent analyses have confirmed good performance status, control of the primary tumour, absence of extracranial metastases and age less than 65 years to be predictors for longer survival. Medical therapy typically includes the use of corticosteroids, and some advances have been made in optimising the use of these agents. Prophylactic use of antiepileptic drugs in patients with brain metastases is generally discouraged. Chemotherapy was previously not considered to have a role in treating brain metastases, but has increasingly become an accepted treatment option. Recent clinical studies have evaluated the integration of chemotherapy with conventional treatments such as radiotherapy and the addition of biological response modifiers. In the past, radiotherapy has been the mainstay of treatment for brain metastases. A number of randomised controlled trials have explored external beam radiation therapy, radiation sensitisers, postoperative whole brain irradiation and prophylactic cranial irradiation. Significant improvements in survival have been demonstrated as a result of prophylactic cranial irradiation in patients with small-cell lung cancer, and improved local control of brain metastases has been achieved with postoperative whole brain irradiation. A number of studies have helped define a more efficient use of external beam irradiation. Radiosurgery in particular has been identified as an important advance in radiation treatment delivery and may provide an acceptable alternative to surgical resection in many patients. Conventional surgery has long had a role to play in establishing the diagnosis, guiding the choice of subsequent therapies and reversing life-threatening complications from brain metastases. The risks of surgery have been reduced with recent improvements in anaesthesia and intraoperative tumour localisation. Recent clinical studies have addressed the role of surgical resection in the management of patients with a single brain metastasis. Survival benefits have been demonstrated in patients undergoing surgical resection in addition to external beam radiation therapy. Despite the improvements achieved in the treatment of patients with brain metastases at first diagnosis, the question of retreatment may arise in due course. The therapeutic options available in this situation include re-operation, radiosurgery and brachytherapy.


Peripheral arteriovenous fistula manifesting as antebrachial dermatopathy in a cat.
CASE DESCRIPTION A 13-year-old neutered male Abyssinian cat with a 4-month history of right forelimb edema and multifocal crusting lesions at the distal aspect of the antebrachium was referred to a veterinary teaching hospital for evaluation. Extensive hemorrhage from the lesions had been observed after self-grooming, and findings on histologic examination of a skin biopsy sample prior to referral were consistent with atypical dermal hemodynamics and inflammation. CLINICAL FINDINGS Diffuse pitting edema and multifocal, 3- to 4-mm-diameter sanguineous crusting lesions affecting the antebrachium were observed distal to a pulsatile subcutaneous mass in the right elbow joint region that had a palpable thrill and auscultable bruit. No systemic abnormalities were detected. TREATMENT AND OUTCOME Contrast-enhanced CT angiography with 3-D reconstruction identified an arteriovenous fistula with a large aberrant vessel coursing distally. Surgical ligation of an arterialized vein distal to the fistula without en bloc resection led to resolution of all clinical signs. The vascular anomaly was no longer patent when diagnostic imaging was repeated 5 months after surgery. CLINICAL RELEVANCE Acquired arteriovenous fistulas can lead to bleeding skin lesions affecting the antebrachium in cats. Surgical ligation of an aberrant reverse-shunting vein distal to the fistula successfully resolved clinical signs in the cat of this report and may warrant investigation as a treatment option in cats with this condition.


Genome-wide identification, characterization, and expression analysis of the MLO gene family in Cucumis sativus.
Mildew resistance locus o (MLO) is a plant-specific seven-transmembrane (TM) gene family. Several studies have revealed that certain members of the MLO gene family mediate powdery mildew susceptibility in three plant species, namely, Arabidopsis, barley, and tomato. The sequenced cucumber genome provides an opportunity to conduct a comprehensive overview of the MLO gene family. Fourteen genes (designated CsMLO01 through CsMLO14) have been identified within the Cucumis sativus genome by using an in silico cloning method with the MLO amino acid sequences of Arabidopsis thaliana and rice as probes. Sequence alignment revealed that numerous features of the gene family, such as TMs, a calmodulin-binding domain, peptide domains I and II, and 30 important amino acid residues for MLO function, are well conserved. Phylogenetic analysis of the MLO genes from cucumber and other plant species reveals seven different clades (I through VII). Three of these clades comprised MLO genes from A. thaliana, rice, maize, and cucumber, suggesting that these genes may have evolved after the divergence of monocots and dicots. In silico mapping showed that these CsMLOs were located on chromosomes 1, 2, 3, 4, 5, and 6 without any obvious clustering, except CsMLO01. To our knowledge, this paper is the first comprehensive report on MLO genes in C. sativus. These findings will facilitate the functional characterization of the MLOs related to powdery mildew susceptibility and assist in the development of disease resistance in cucumber.


Evaluation of Hypersensitivity Reactions with Leuprolide Acetate and Triptorelin Acetate in Children.
Gonadotropin releasing hormone analogues (GnRHa) are commonly used to treat central precocious puberty (CPP). Generally, they are well-tolerated; however adverse reactions have been reported. Local adverse events occur in 10-15% of the patients who were treated with GnRHa. Anaphylactoid reactions with GnRHa are very rarely seen. The aim of this study is to report our clinical experience with hypersensitivity reactions seen in pediatric patients receiving leuprolide acetate (LA) and triptorelin acetate (TA) in CPP at the single pediatric tertiary medical center and to evaluate the incidence rate of hypersensitivity reactions. This retrospective study included children with CPP who were treated with GnRHa (LA and TA) at our hospital between January 2013 and December 2020. We analyzed clinical characteristics of patients who experienced adverse reactions and analyzed the incidence rate. Seven side effects (adverse reactions) (0.69%) were observed among total of 1010 CPP patients who were treated with TA and LA. Sterile abscesses were observed in 3 patients (0.29%). None of the patients had an anaphylaxis. Tremors of both hands, a vomiting episode, an urticarial rash, and musculoskeletal stiffness were observed in one patient each. In our study, mild reactions were seen in 7 patients. GnRHa can be safely used and well-tolerated medications; but exceedingly rare, severe reactions can be developed.


Barrett's esophagus.
Barrett's esophagus is an acquired metaplastic abnormality in which the normal stratified squamous epithelium lining of the esophagus is replaced by an intestinal-like columnar epithelium. While in itself a benign and asymptomatic disorder, the clinical importance of this relatively common condition relates to its role as a precursor lesion to esophageal adenocarcinoma, the incidence of which has dramatically increased in Western populations in recent years. Although known to arise as a consequence of chronic gastroesophageal reflux, the cellular and molecular mechanisms underlying development Barrett's esophagus and its progression to cancer remain unclear.


Community participation in malaria control in olorunda local government area, osun state, southwestern Nigeria.
Malaria is a major health burden in developing countries and needs multiple strategies for its control. Community participation as one of the strategies for malaria control promotes self-awareness and confidence, causes the people to examine the problems and to think positively about the solutions. The study was aimed at assessing the level of community participation in malaria control in Olorunda local government area of Osogbo, Osun state, Nigeria. The study employed a cross-sectional descriptive design. Multi-staged sampling technique was used to choose 550 respondents. An interviewer-administered semi-structured questionnaire was used to elicit information from the respondents. Most of the respondents (65.0%) fell between the age ranges 20-39 years, with a mean age of 32.85 ± 12 years. Almost all (98.4%) respondents had knowledge of malaria with most of them (88.0%) correctly aware that mosquito bite could lead to malaria fever. Respondents stated that stagnant pool (92.6%) and refuse dump (89.0%) could predispose to malaria. About two-thirds (60.6%) of the respondents participated in the control of the breeding sites of mosquitoes on specific days for environmental sanitation. The association between community participation in health talk and community participation in malaria control was statistically significant (p<0.000). Although only 23.0% use ITN to protect themselves from mosquito bites, there was statistical significant association between awareness of respondents about ITN and its usage (p=0.003). Knowledge of respondents about malaria was high with majority participating in malaria control measures. However, the use of insecticide treated nets (ITN) was low. Therefore, it is recommended that continuous awareness creation on the use of ITN, and continued efforts aimed at elimination of breeding sites of mosquitoes should be adopted to achieve long term control of malaria.


Nanostructuring Confinement for Controllable Interfacial Charge Transfer.
Carbon nanostructures supported semiconductors are common in photocatalytic and photoelectrochemical applications, as it is expected that the nanoconductors can improve the spatial separation and transport of photogenerated charge carriers. Transfer of charge carriers through the carbon-semiconductor interface is the key electronic process, which determines the role of charge separation channels, and is sensitively influenced by band structures of the semiconductor near the contacts. Usually, this electronic process suffers from excessive energy dissipation by thermionic emission, which will undesirably prevent the interfacial charge transfer and eventually aggravate the recombination of photogenerated charge carriers. Unfortunately, this critical issue has hardly been consciously considered. Here, ultrathin dopant-free tunneling interlayers coated on the surface of graphene and sandwiched between the carbon sheets and the semiconductor nanostructures are adopted as a model system to demonstrate energy saving for the interfacial charge transfer. The nanostructuring confinement of band bending within the ultrathin interlayers in contact with the graphene sheets effectively narrows the width of the potential barriers, which enables tunneling of a substantial number of photogenerated electrons to the co-catalysts without unduly consuming energy. Besides, the dopant-free tunneling interlayers simultaneously block the transferred electrons in the sandwiched graphene sheets from leakage.


Ligand-selective interdomain conformations of estrogen receptor-alpha.
Selective estrogen receptor modulators (SERMs) inhibit estrogen activation of the estrogen receptor (ER) in some tissues but activate ER in other tissues. These tissue-selective actions suggest that SERMs may be identified with tissue specificities that would improve the safety of breast cancer and hormone replacement therapies. The identification of an improved SERM would be aided by understanding the effects of each SERM on the structure and interactions of ER. To date, the inability to obtain structures of the full-length ER has limited our structural characterization of SERM action to their antiestrogenic effects on the isolated ER ligand binding domain. We studied the effects of estradiol and the clinically useful SERMs 4-hydroxytamoxifen and fulvestrant on the conformation of the full-length ERalpha dimer complex by comparing, in living human breast cancer cells, the amounts of energy transfer between fluorophores attached to different domains of ERalpha. Estradiol, 4-hydroxytamoxifen, and fulvestrant all promoted the rapid formation of ERalpha dimers with equivalent interaction kinetics. The amino- and carboxyl-terminal ERalpha domains both contain activation functions differentially affected by these ligands, but the positions of only the carboxyl termini differed upon binding with estradiol, 4-hydroxytamoxifen, or fulvestrant. The association of a specific ERalpha dimer conformation with the binding of ligands of different clinical effect will assist the identification of a SERM with optimal tissue-selective estrogenic and antiestrogenic activities. These studies also provide a roadmap for dissecting important structural and kinetic details for any protein complex from the quantitative analysis of energy transfer.


[Treatment of squamous cell carcinomas with prolonged, continuous infusions of bleomycin and cisplatinum. A first series of 80 cases with 75% objective response (author's transl)].
Eighty consecutive patients with measurable and assessable squamous cell carcinoma of the head or neck, lung, oesophagus and uterine cervix received one to four courses of combined bleomycin and cis-platinum treatment. Each course lasted 5 to 6 days during which bleomycin was administered by continuous intravenous infusion and cis-platinum was given daily. If there was no evidence of toxicity or progressive disease, courses were repeated every 3 weeks to a total bleomycin dose of 150 mg/m2. A 75% objective response rate was obtained, with one case of progressive disease and no prohibitive toxic reaction. These results suggest that cytostatic drugs with low bone marrow toxicity can be given for prolonged periods and throw some doubt on the alleged resistance of squamous cell carcinomas to chemotherapy.


PeP-SCOT a health coaching intervention for people in prisons: the development of the intervention protocol.
There is a need for an alternative approach for health promotion prisons since previous work has indicated that health education, while improving health knowledge, does not result in behaviour change. Evidence has suggested that a health coaching assists in this regard. However, the question remained whether this approach would be appropriate and possible in prisons? This paper presents the public health strategies used to work in partnership with prison management to address challenges and accept opportunities as a health coaching intervention protocol was developed for oral health and wellbeing in the prison setting.


Discovery of selective covalent cathepsin K inhibitors containing novel 4-cyanopyrimidine warhead based on quantum chemical calculations and binding mode analysis.
Cathepsin K (Cat K), mainly expressed by osteoclasts, plays an important role in bone resorption. Covalent Cat K inhibitors will show great potential in the future treatment of osteoporosis. It has been reported that the selectivity of covalent cathepsin K inhibitors was related to the drug's safety. The type of warhead has a crucial influence on the enzyme bioactivity and selectivity of covalent inhibitors. In order to develop novel covalent inhibitors with the selective new warhead, quantum chemical calculations were performed to estimate the reactivity of the nitrile warheads. Moreover, binding mode analysis between ligands and high homology Cat K, S and B revealed differences in non-covalent interactions. Novel covalent Cat K inhibitors containing 4-cyanopyrimidine warhead (11) were determined for the first time. Among them, compound 34 significantly inhibited Cat K (IC50 = 61.9 nM) with excellent selectivity compared to Cat S (>810-fold) and Cat B (>1620-fold), respectively. Binding mode analysis of Cat K-34 complex provided the basis for further optimization. Compound 34 could be a valuable lead compound for further research on safe and effective Cat K inhibitors.


Perception in dynamic scenes: What is your Heider capacity?
The classic animation experiment by Heider and Simmel (1944) revealed that humans have a strong tendency to impose narrative even on displays showing interactions between simple geometric shapes. In their most famous animation with three simple shapes, observers almost inevitably interpreted them as rational agents with intentions, desires, and beliefs ("That nasty big triangle!"). Much work on dynamic scenes has identified basic visual properties that can make shapes seem animate. Here, we investigate the limits on the ability to use narrative to share information about animated scenes. We created 30 second Heider-style cartoons with 3-9 items. Item trajectories were generated automatically by a simple set of rules, but without a script. In Experiments 1 and 2, 10 observers wrote short narratives for each cartoon. Next, new observers were shown a cartoon and then presented with a narrative generated for that specific cartoon or one generated for a different cartoon having the same items. Observers rated the fit of the narrative to the cartoon on a scale from 1 (clearly does not fit) to 5 (clearly fits). Performance declined markedly when the number of items was larger than 3. Experiment 3 had observers determine if a short clip of a cartoon came from a longer clip. Experiment 4 had observers determine which of two narratives fit a cartoon. Finally, in Experiment 5, narratives always mentioned every item in a display. In all cases of matching narrative to cartoon, performance drops most dramatically between 3 and 4 items. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Consultation by the United Kingdom to South Africa to develop human diversity teaching.
This paper describes consultation provided by the University of Leicester to the Medical University of Southern Africa (Medunsa) funded through British Council and the Department for International Development to develop a course addressing issues of diversity at Medunsa. The aims of the link were essentially for Leicester to provide support and guidance on the development of aspecific module. This inevitably included the provision of training in key areas such as teaching skills and evaluation of teaching. This paper focuses on the potential difficulties of such a link, which included cultural differences, issues of hierarchy and student influence. The project outcomes have been the development of a coherent module on human diversity which is assessed in such a way as to support the development of student writing skills, increased staff teaching skills and a joint conference to disseminate the learning that has taken place from the project.


[Influence of GLP-1 on oxidative stress injury in non-alcoholic fatty liver disease rats].
To investigate the effects of glucagon-like peptide-1 (GLP-1) on liver oxidative stress injury using a rat model of non-alcoholic fatty liver disease. Sixty male Sprague-Dawley rats were fed 12 weeks of either a diet of normal chow (NC), for use as controls (n =15) or high-fat chow (HF), for use as models (n =45).The NC rats were administered normal saline, while the HF rats were treated with either normal saline (NS), for use as untreated model controls (n =10), low-dose GLP-1 (LG, 50 mutg/kg; n =10), mid-dose GLP-1 (MG, 100 mutg/kg; n =10), or high-dose GLP-1 (HG, 200 mug/kg; n =10); all treatments lasted for 4 weeks.The rats' weight, levels of serum biochemical markers (triglycerides, total cholesterol, high-density lipoproteincholesterol, low-density lipoprotein-cholesterol, alanine arninotransferase, and aspartate aminotransferase), levels of superoxide dismutase (SOD) and malondialdehyde (MDA), and expression of CYP2E1 mRNA and protein in liver homogenates were measured.The F test, t-test, least significant difference test and Dunnett's T3 test were used for statistical analyses. Compared with the NC group, the rars in the NS group showed significantly lower SOD (165.81 ± 11.64 vs.192.89 ± 16.53 U/mg, P < 0.05), significantly higher MDA (7.30 ± 1.79 vs.3.10 ± 1.30 nmol/ mg, P < 0.05), and significantly higher expressions of CYP2E1 mRNA and protein (both P < 0.05).After GLP1 treatment, the rats in the LG, MG and HG groups showed increased levels of SOD (compared to the NS group; 171.44 ± 9.80 vs.177.66 ± 14.77 vs.186.17 ± 15.43 U/mg; only the HG group had P < 0.05), significantly decreased levels of MDA (compared to the NS group; 5.16 ± 1.45 vs.4.08 ± 1.22 vs.3.31 ± 1.14 nmol/mg; all P < 0.05], and decreased levels of CYP2E1 mRNA and protein expressions (CYP2E1 mRNA:only the HG group had P < 0.05; CYP2E1 protein: both the MG and HG groups had P < 0.05). GLP-1 treatment can improve oxidative stress injury, suggesting its potential as a therapeutic agent for non-alcoholic fatty liver disease.


Multicenter Phase II Study of a New Effective S-1 and Irinotecan Combination Schedule in Patients with Unresectable Metastatic or Recurrent Colorectal Cancer.
This multicenter phase II study determined the efficacy and safety of new daily oral S-1 and weekly irinotecan (CPT-11) combination schedule in patients with previously untreated advanced or recurrent colorectal cancer. Patients received first-line chemotherapy comprising S-1 80 mg/m(2)/day given on days 3 to 7, 10 to 14, and 17 to 21 and 60 mg/m(2) CPT-11 administered intravenously on days 1, 8, and 15 of a 28-day cycle. A total of 45 eligible patients were enrolled in this study. The overall response rate was 48.9%. Median progression-free survival and median overall survival was 8.1 months and 20.9 months, respectively. The rates of grade 3 or 4 toxicity were as follows: neutropenia, 8.9%; anemia, 4.4%; anorexia, 6.7%; and diarrhea, 6.7%. This new S-1 and irinotecan combination schedule appeared to be an effective, well-tolerated, and convenient regimen in patients with advanced colorectal cancer as compared with conventional regimens such as FOLFIRI and IRIS.


Treatment of cervical spine fractures with halo vest method in children and young people.
The Halo Vest method is a non-invasive treatment of cervical spine fractures. It is successfully applied in adults, which is supported by numerous studies, but has rarely been used among children and young people. There is little published research in this field. The aim of the paper is to present the effectiveness of Halo Vest external fixation in children and to evaluate the complication rate of this method. A retrospective study of 6 patients with cervical spine fractures with an average age of 13.3 years (range: 10 to 17 years) treated with Halo Vest external fixation between 2004 and 2013. The type and cause of fracture, treatment outcome and complications were evaluated. The average duration of follow-up was 55 months. In 5 cases, the treatment result was satisfactory. In one case, there were complications in the form of an external infection around the cranial pins. 1. The Halo Vest system can be applied as a non-operative method of treating cervical spine fractures in children and young people. 2. The criteria of eligibility for specific types of cervical spine fracture treatment in children and young people require further investigation, especially with regard to eliminating complications.


Root and shoot parts of strawberry: factories for production of functional human pro-insulin.
Diabetes, a disease caused by excessive blood sugar, is caused by the lack of insulin. For commercial production, insulin is made in bacteria or yeast by protein recombinant technology. The focus of this research is evaluating another resource and producing of recombinant insulin protein in as strawberry as this plant has high potential in production of pharmaceutical proteins. Strawberry is a suitable bioreactor for production of recombinant proteins especially edible vaccines. In this research, human pro-insulin gene was cloned in pCAMBIA1304 vector under CaMV35S promoter and NOS terminator. Agrobacterium tumefaciens LBA4404, AGL1, EHA105, EHA101, C58, C58 (pGV2260) and C58 (pGV3101) strains were used for transformation of pro-insulin gene into strawberry cv. Camarosa, Selva, Sarian Hybrid, Pajaro, Paros, Gaviota, Alpine. Additionally, Agrobacterium rhizogenes K599, R1000, A4 and MSU440 strains were utilized for gene transformation into hairy roots. PCR analysis indicated the presence of transformed human pro-insulin gene in the strawberry and hairy roots. Also, its transcription was confirmed using RT-PCR. Furthermore, the analysis of plants, fruits and hairy roots at the level of proteins using dot blot, ELISA, SDS-PAGE and ECL tests re-confirmed the expression of this protein in the transgenic plants as well as hairy roots. Protein purification of human pro-insulin from transgenic tissues was performed using affinity chromatography. Finally, the bioassay of recombinant pro-insulin was performed. The analysis of second generations of transgenic plants (T1) at DNA and protein levels was also performed as a complementary experiment. This study opens a new avenue in molecular farming of human pro-insulin through its mass production in roots and shoots of strawberry.


Formula to detect high sodium excretion from spot urine in chronic kidney disease patients.
Excessive sodium intake is related to adverse renal and cardiovascular outcomes in patients with chronic kidney disease (CKD) and assessment of sodium intake is complex and not evaluated very often in clinical practice. To develop a new formula to estimate 24h sodium excretion from urine sample (second void) of patients with CKD. We included 51 participants with CKD who provided 24-hour urine collection and a sample of the second urine of the day to determine the sodium excretion. A formula to estimate the 24-hour sodium excretion was developed from a multivariate regression equation coefficients. The accuracy of the formula was tested by calculating the P30 (proportion of estimates within 30% of measured sodium exection) and the ability of the formula to discriminate sodium intake higher than 3.6 g/day was evaluated by ROC curve. Correlation test between measured and estimated sodium was significant (r = 0.57; p < 0.001), but P30 test identified a low accuracy (61%) of the formula. Different cutoff points were tested by performance tests and a ROC curve was generated with the cutoff that showed better performance (3.6 g/day). An area under the curve of 0.69 with a sensitivity of 0.91 and specificity of 0.53 was obtained. A simple formula with high sensitivity in detecting patients with sodium consumption higher than 3.6 g/day from isolated urine sample was developed. Studies with a higher number of participants and with different populations are necessary to test formula´s validity.


Oxisuran and immune reactions: mediation of oxisuran action by the adrenal glands.
Oxisuran was tested in a TAR system and for the DH on SRBC. Besides immunosuppressive properties in the TAR and DH also mentioned by other authors, stimulation was found after prolonged administration. No effect of oxisuran on the humoral response was observed. The action of oxisuran was suggested to be indirect, effected by stimulation of the PAG system. Adrenalectomy of mice made animals non-liable for oxisuran action measured in the TAR assay. Oxisuran caused an increase of the corticosterone plasma level with a peak after four daily injections. This was paralleled by a peak in adrenal gland weight and a minimum in thymus size. The reduction in these effects after five injections (tachyphylaxis) suggest that a feedback mechanism is involved. Comparison of thymus weights after oxisuran and corticosterone administration indicates that a daily dose of 100 mg oxisuran/kg corresponds with 1.5 mg corticosterone/kg. The effects of oxisuran in the TAR and on the DH and the feedback phenomenon could be imitated with 1.5 mg corticosterone/kg. The mononuclear phagocyte has been proposed as the main target cell of oxisuran action, mediated by the PAG system.


Key Strategies for Physical Activity Interventions Among Older Women: Process Evaluation of a Clinical Trial.
To describe strategies salient to physical activity (PA) initiation and maintenance among older women who participated in a clinical trial that tested a PA intervention. A descriptive phenomenological, qualitative design for a process evaluation of a successful clinical trial. Senior primary care clinics associated with a large medical center in a southern state. A total of 20 older women at least 60 years without advanced frailty. Purposive sampling using maximum variation technique was used to select participants. A semi-structured interview guide facilitated individual, in-depth interviews lasting 45 to 90 minutes. Narratives were analyzed using content analysis with constant comparison technique to summarize the data. Eight African American and 12 white older women with a mean age of 68 from control and intervention arms participated. Five central themes described salient strategies to promote and maintain PA: sensed benefits, motivation, and self-efficacy were central to success, while a reduction in barriers was essential before maintaining PA. The last theme, a life-changing awareness indicated that PA had become a shared value. An explanatory model describing interrelationships is presented. This study suggests key strategies to include in PA interventions with older women. An unexpected finding was that PA became a shared value, an action promoted by the Culture of Health initiative to improve population health and well-being.


The treatment challenge of heterotopic ossification in a patient with Parkinson's disease and stroke.
Neurogenic heterotopic ossification (HO) is characterized by bone formation in a non-anatomical site. It is usually seen in patients with spinal cord injury and traumatic brain injury. It occurs less frequently in other types of acquired brain injury. Neurogenic HO has only been recorded in a few cases of Parkinson's disease (PD). Its treatment is challenging and may need pain palliation methods. The course and treatment approach of a complicated case with PD and stroke who developed HO of the hip joints during rehabilitation was discussed in this article. A 79-year-old male patient with stroke and PD experienced restriction and pain in both hip joints. Bilateral HO was discovered on a pelvic radiograph. He did not benefit from exercises, transcutaneous electrical nerve stimulation, or indomethacin. Radiotherapy has also been tried to treat HO. Following that, obturator and femoral nerve blocks were used to relieve pain, and pain was reduced and sitting balance improved. HO is a rare complication of PD and stroke that has an adverse effect on the rehabilitation process. Since treatment choices are limited, palliative pain management approaches such as peripheral nerve block may be considered.