Potential Role of Chronic Physical Exercise as a Treatment in the Development of Vitiligo.
Vitiligo is an autoimmune disease characterized by progressive skin depigmentation and the appearance of white patches throughout the body caused by significant apoptosis of epidermal melanocytes. Despite not causing any physical pain, vitiligo can originate several psychosocial disorders, drastically reducing patients' quality of life. Emerging evidence has shown that vitiligo is associated with several genetic polymorphisms related to auto-reactivity from the immune system to melanocytes. Melanocytes from vitiligo patients suffer from excess reactive oxygen species (ROS) produced by defective mitochondria besides a poor endogenous antioxidant system (EAS). This redox imbalance results in dramatic melanocyte oxidative stress (OS), causing significant damage in proteins, lipid membranes, and DNA. The damaged melanocytes secret damage-associated molecular pattern (DAMPs), inducing and increasing inflammatory gene expression response that ultimately leads to melanocytes apoptosis. Vitiligo severity has been also associated with increasing the prevalence and incidence of metabolic syndrome (MetS) or associated disorders such as insulin resistance and hypercholesterolemia. Thus, suggesting that in genetically predisposed individuals, the environmental context that triggers MetS (i.e., sedentary lifestyle) may also be an important trigger for the development and severity of vitiligo disease. This paper will discuss the relationship between the immune system and epidermal melanocytes and their interplay with the redox system. Based on state-of-the-art evidence from the vitiligo research, physical exercise (PE) immunology, and redox system literature, we will also propose chronic PE as a potential therapeutic strategy to treat and prevent vitiligo disease progression. We will present evidence that chronic PE can change the balance of inflammatory to an anti-inflammatory state, improve both EAS and the mitochondrial structure and function (resulting in the decrease of OS). Finally, we will highlight clinically relevant markers that can be analyzed in a new research avenue to test the potential applicability of chronic PE in vitiligo disease.


Computational study of cell adhesion and rolling in flow channel by meshfree method.
Tethering and rolling of circulating leukocytes on the surface of endothelium are critical steps during an inflammatory response. A soft solid cell model was proposed to study monocytes tethering and rolling behaviors on substrate surface in shear flow. The interactions between monocytes and micro-channel surface were modeled by a coarse-grained molecular adhesive potential. The computational model was implemented in a Lagrange-type meshfree Galerkin formulation to investigate the monocyte tethering and rolling process with different flow rates. From the simulation results, it was found that the flow rate has profound effects on the rolling velocity, contact area and effective stress of monocytes. As the flow rate increased, the rolling velocity would increase linearly, whereas the contact area and average effective stress in monocyte showed nonlinear increase.


Hematological indices in an older population sample: derivation of healthy reference values.
Factors affecting hematological values were explored, and healthy reference values were estimated from a cross-sectional survey of a population (n = 4433), ages 49 years or more, residing permanently in a defined geographic region. Nursing home residents were excluded. Details of medication use and medical history were obtained by interview, and participants were asked to return after an overnight fast for blood sampling. The participation rate was 82.4%, of whom 88.4% provided a fasting blood sample. Hemoglobin, hematocrit, and erythrocyte counts were higher in men, whereas platelet counts were higher in women. Statistical associations between each hematological index and smoking, alcohol intake, use of certain drugs, chronic disease, and high creatinine values were tested by unpaired t-tests. Separate reference groups were defined for each hematological index by excluding subjects with any of the factors found to be of importance. The resulting reference values are particularly appropriate for evaluating hematological test results in older individuals.


Multiscale dynamics and robust critical scaling in a continuum current sheet model.
We analyze the self-organized critical behavior of a continuum running avalanche model. We demonstrate that over local interaction scales, the model behavior is affected by low-dimensional chaotic dynamics that plays the role of the primary noise source. With the help of scale-free avalanches, the uncertainty associated with chaos is distributed over a variety of intermediate scales and thus gives rise to spatiotemporal fluctuations that are characterized by power-law distribution functions. We show that globally, the continuum model displays structurally stable critical scaling that can be observed in a finite region in the control parameter space. In this region, the system exhibits a power-law critical divergence of the integrated response function over a broad range of dissipation rates. The observed behavior involves a remarkably stable spatial configuration. We explain the robust features of the model by the adjustable dynamics of its global loading-unloading cycle, which allows maintaining the long-term stationary state without affecting the intrinsic avalanche dynamics.


"Any movement at all is exercise": a focused ethnography of rural community-dwelling older adults' perceptions and experiences of exercise as self-care.
To understand rural community-dwelling older adult participants' shared values, beliefs, and behaviours related to exercise as self-care. We conducted a constructivist-focused ethnography involving semi-structured interviews and participant observation with 17 individuals 65 years and older. Interviews were transcribed and inductively coded to develop themes related to exercise, self-care, and exercise as self-care. Field notes were triangulated with follow-up interviews and dialogue between authors to enhance interpretation. Participants described exercise broadly as movement and not as a central self-care behaviour. However, awareness of the importance and health-related benefits of exercise increased after a significant personal health-related event. Participants preferred exercise that was enjoyable and previously experienced. Prescribing exercise for older adults may be particularly effective if the focus is on enjoyable and previously experienced physical activity and if it incorporates interpretation of exercise guidelines and training principles in relation to chronic conditions and potential health benefits.


Gene Delivery with Organic Electronic Biomaterials.
Gene therapy may be capable of treating a variety of diseases, a prerequisite of which is the successful delivery of polynucleic acids (e.g., DNA, RNA) to a patient's cells. Delivery can be achieved technologically (e.g., using electroporation), using viruses (natural gene delivery vectors) or non-viral vectors (e.g., lipids, nanoparticles, polymers). This article aims to give the reader an overview of the use of organic electronic materials (i.e., fullerenes, graphenes and conjugated polymers) as non-viral gene delivery vectors.


Renal leiomyoma: a contemporary multi-institution study of an infrequent and frequently misclassified neoplasm.
Renal leiomyoma is an exceptionally rare benign mesenchymal tumor of the kidney predominantly arising in proximity of the renal capsule or pelvis. Its rarity and nonspecific clinical and imaging features may lead to radical or partial nephrectomy on the basis of preoperative suspicion of renal cell carcinoma. The diagnosis of renal leiomyoma is challenging because of the histologic overlap with lipid-poor angiomyolipoma (AML). We conducted a multi-institution study to characterize renal leiomyoma in greater detail. We collected and reviewed 24 cases diagnosed initially as renal leiomyoma in 10 institutions from North America, Canada, and Europe. Immunohistochemical expression of desmin, HMB-45, estrogen receptor (ER), progesterone receptor (PR), and cathepsin K was evaluated. Upon central review, 9 tumors were classified as renal leiomyoma, whereas the remaining were reclassified as AML (n=13), myolipoma (n=1), and medullary fibroma (n=1). All renal leiomyomas were solitary and occurred in female patients (mean age 63 y; range, 44 to 74 y). Tumor size ranged from 0.6 to 7.0 cm (mean 2.9 cm); 7 originated from the renal capsule or the subcapsular area and 1 from a large vessel in the renal sinus. All leiomyomas were diffusely positive for desmin and negative for HMB-45 and cathepsin K; 6/9 (67%) showed diffuse ER and PR expression, and 1 case showed focal ER positivity only. Renal leiomyoma should be included in the histologic differential diagnosis of solid renal masses, particularly in perimenopausal women. The main differential diagnosis is with lipid-poor AML, and cathepsin K plays a key role in distinguishing these 2 lesions.


Manipulating Dispersions of Magnetic Nanoparticles.
Dispersions of magnetic nanoparticles (MNPs) can exhibit paramagnetic ferrofluid or ferromagnetic liquid behavior. By modifying the surface functionality of MNPs, ferrofluids have been used to fabricate novel magnetically actuated devices. If the surface-functionalized MNPs interact with complementary ligands at a fluid-fluid interface, MNP surfactants form and in situ assemble at the interface. When jammed interfacially, MNP surfactants give rise to ferromagnetic behavior of the liquid (droplet), which is endowed with permanent magnetic dipoles while maintaining all of the characteristics of a fluid system. Here, we give a brief overview of the developments in the dispersion of MNPs in liquids from ferrofluids to ferromagnetic liquid droplets, their responses to external fields, and the manipulation of these responses for end uses. The reversible room-temperature para-to-ferro transformation of magnetic liquids is highlighted. We discuss challenges in the synthesis and characterization of these unusual liquids along with potential technological applications.


An anatomic index for the severity of ocular injuries.
Ocular injuries are a frequent cause of monocular blindness and cause disfigurement and discomfort. We developed a measure of severity for eye injuries using a multi-attribute utility (MAU) model. The severity index scoring was applied to eye injuries that presented at hospitals in Wisconsin, U.S.A. The resulting distribution of severities was compatible with that seen by general eye care physicians. A severity scale provides a means of comparing the severity of injuries from a wide variety of traumatic sources (e.g. automobile crashes, combat injuries, occupational accidents, etc.) and is useful in evaluating preventive and public health measurements.


Oct4 expression in gastric carcinoma: association with tumor proliferation, angiogenesis and survival.
Octamer-binding transcription factor 4 (Oct4) is a transcription factor that has an important role in stem cell differentiation and self-renewal. Oct4 has also been implicated in tumorigenicity of different cancers. This study aimed to analyze Oct4 expression in gastric carcinoma (GC) and to evaluate the relation between Oct4 expression and clinicopathologic parameters, tumor proliferation, and angiogenesis in addition to patient survival. Oct4 mRNA was detected by quantitative reverse transcription PCR (qRT-PCR) in 45 GC specimens and adjacent non-cancerous tissues. We found a significant difference in Oct4 mRNA relative expression levels in GC tissue compared with adjacent non-cancerous tissues (p < 0.001). Furthermore, immunohistochemistry (IHC) was performed to study the Oct4 expression in GC cases. High Oct4 immunostaining was detected in 62.2% of GC specimens. High Oct4 expression both by mRNA relative quantitation and IHC were significantly related to poorly differentiated tumors, nodal metastasis, and stage III tumors. Moreover, high Oct4 IHC expression was also associated with cases positive for Ki-67 and VEGF expressions (p < 0.001 and 0.021, respectively). Oct4 expression identified by both mRNA relative quantitation and IHC was significantly related (p < 0.001). As regards patient survival, high Oct4 expression was significantly related to poor overall survival (OS) and disease-free survival (DFS) (p = 0.029 and 0.031, respectively). Oct4 plays a valuable role in the progression and prognosis of GC. High Oct4 expression is associated with high tumor grade, nodal metastasis, stage III tumors, and poor OS and DFS. High Oct4 is also significantly associated with Ki-67 and VGEF expression, thus enhancing tumor proliferation and angiogenesis.


A Nano-MgO and Ionic Liquid-Catalyzed 'Green' Synthesis Protocol for the Development of Adamantyl-Imidazolo-Thiadiazoles as Anti-Tuberculosis Agents Targeting Sterol 14α-Demethylase (CYP51).
In this work, we describe the 'green' synthesis of novel 6-(adamantan-1-yl)-2-substituted-imidazo[2,1-b][1,3,4]thiadiazoles (AITs) by ring formation reactions using 1-(adamantan-1-yl)-2-bromoethanone and 5-alkyl/aryl-2-amino1,3,4-thiadiazoles on a nano material base in ionic liquid media. Given the established activity of imidazothiadiazoles against M. tuberculosis, we next examined the anti-TB activity of AITs against the H37Rv strain using Alamar blue assay. Among the tested compounds 6-(adamantan-1-yl)-2-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole (3f) showed potent inhibitory activity towards M. tuberculosis with an MIC value of 8.5 μM. The inhibitory effect of this molecule against M. tuberculosis was comparable to the standard drugs such as Pyrazinamide, Streptomycin, and Ciprofloxacin drugs. Mechanistically, an in silico analysis predicted sterol 14α-demethylase (CYP51) as the likely target and experimental activity of 3f in this system corroborated the in silico target prediction. In summary, we herein report the synthesis and biological evaluation of novel AITs against M. tuberculosis that likely target CYP51 to induce their antimycobacterial activity.


Role of CXCR3-induced donor T-cell migration in acute GVHD.
The chemokine receptor CXCR3 has an important role in the migration of effector T cells. To investigate the role of CXCR3 on donor cells in acute graft vs host disease (GVHD) we used a well-defined experimental bone marrow transplantation (BMT) model where acute GVHD is mediated by donor CD8(+) T cells against minor histocompatibility antigens. METHODS; Lethally irradiated C3H.SW recipients were transplanted from either wild-type B6 or CXCR3(-/-) B6 donors. Donor T-cell expansion was analyzed in the spleen and small intestine of recipients by FACS. Donor T-cell function was analyzed by cytokine secretion. The severity of acute GVHD was assessed by histopathological analysis of intestine and liver, GVHD clinical scores, and survival after BMT. Significantly higher numbers of donor CD8(+) CXCR3(-/-) T cells were found in the spleen on days +7 and +14 compared to donor wild-type T cells. By contrast, the number of CD8(+) T cells in the small bowel of BMT recipients from CXCR3(-/-) donors was sevenfold lower than from wild-type donors. Systemic concentrations of INF-gamma and TNF-alpha were equivalent between groups. Animals that received CXCR3(-/-) donor T cells demonstrated diminished GI tract and liver damage and showed improved survival after BMT compared to recipients of wild-type donor cells (43% vs 0%, p<0.001). The migration of donor CD8(+) T cells to GVHD target organs such as the intestine depends on the expression of CXCR3 and contributes significantly to GVHD damage and overall mortality.


First-principle molecular dynamics with ultrasoft pseudopotentials: parallel implementation and application to extended bioinorganic systems.
We present a plane-wave ultrasoft pseudopotential implementation of first-principle molecular dynamics, which is well suited to model large molecular systems containing transition metal centers. We describe an efficient strategy for parallelization that includes special features to deal with the augmented charge in the contest of Vanderbilt's ultrasoft pseudopotentials. We also discuss a simple approach to model molecular systems with a net charge and/or large dipole/quadrupole moments. We present test applications to manganese and iron porphyrins representative of a large class of biologically relevant metalorganic systems. Our results show that accurate density-functional theory calculations on systems with several hundred atoms are feasible with access to moderate computational resources.


An Online Cross-Sectional Survey on Oral Healthcare Among School-Age Children During COVID-19 Epidemic in Wuhan, China.
Background: Since the outbreak of Coronavirus disease 2019 (COVID-19), the government of China adopted many measures which changed people's lifestyle including oral health-related lifestyle to control the transmission. The aim of this study was to investigate oral health status, oral healthcare behaviors, and parental attitudes toward oral healthcare among school-age children in Wuhan during the COVID-19 outbreak and what the status would be when the outbreak is under control. Methods: This study was an online cross-sectional survey facing elementary school students in Wuhan. The questionnaire was completed by children's parents or other family members. The information on demographic data, oral health status, oral healthcare behaviors, and parental attitudes toward oral healthcare was collected at the end of school closure. The chi-square test was used to test the association of different questionnaire items. Results: A total of 18,383 subjects aged 6-13 years with complete data were included in this investigation, and 44.2% of them suffered pain or discomfort related to teeth and gums during the epidemic. While there might be an increasing need and concern of oral healthcare during the outbreak and even when the outbreak was controlled, the worry of infection made it difficult for people to meet their demands of dental attendance. Conclusion: The risk of cross-infection during the treatment had a negative influence on parental attitudes toward dental attendance. Effective measures should be taken to meet people's demands of dental attendance.


Differentiation of papillary renal cell carcinoma subtypes on CT and MRI.
The objective of our study was to determine the frequency of atypical papillary renal cell carcinomas (RCCs) and identify imaging differences between type 1 and type 2 papillary RCCs once atypical papillary RCC tumors have been excluded. Eighty-two papillary RCC tumors were classified at pathology as type 1, type 2, or atypical. The CT and MRI examinations of these tumors were reviewed. Imaging features such as tumor size, margins, heterogeneity, and enhancement were assessed and the findings in type 1 and type 2 tumors were compared. There were 43 type 1 and 13 type 2 tumors. Atypical histologic features (i.e., tumors containing both type 1 and type 2 components, clear cells, or components with atypically high nuclear grade [in type 1 tumors] or low nuclear grade [in type 2 tumors]) were seen in 26 tumors. On CT, type 2 tumors more commonly had infiltrative margins (p = 0.05) and were more likely to have calcifications (p = 0.04) than type 1 tumors, although these features were seen in all tumor types. Type 2 tumors were also more heterogeneous than type 1 tumors (p = 0.04). On CT, 11 papillary RCCs showed enhancement of less than 20 HU, seven of which showed enhancement of less than 10 HU. On MRI, all tumors showed enhancement on subtraction images. Nearly one third of papillary RCCs in our patient population had atypical features at histology. On CT and MRI, there are some significant differences in imaging features between type 1 and type 2 tumors; however, substantial overlap precludes categorization on a per-patient basis. On CT, many papillary RCCs do not enhance, indicating that assessment of enhancement alone is insufficient for differentiating papillary RCCs from hyperdense cysts.


Milk is not just food but most likely a genetic transfection system activating mTORC1 signaling for postnatal growth.
Milk has been recognized to represent a functionally active nutrient system promoting neonatal growth of mammals. Cell growth is regulated by the nutrient-sensitive kinase mechanistic target of rapamycin complex 1 (mTORC1). There is still a lack of information on the mechanisms of mTORC1 up-regulation by milk consumption. This review presents milk as a materno-neonatal relay system functioning by transfer of preferential amino acids, which increase plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), insulin, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) for mTORC1 activation. Importantly, milk exosomes, which regularly contain microRNA-21, most likely represent a genetic transfection system enhancing mTORC1-driven metabolic processes. Whereas human breast milk is the ideal food for infants allowing appropriate postnatal growth and species-specific metabolic programming, persistent high milk signaling during adolescence and adulthood by continued cow´s milk consumption may promote mTORC1-driven diseases of civilization.


Organocatalytic Enantioselective Cross-Dehydrogenative Coupling of N-Carbamoyl Cyclic Amines with Aldehydes.
The existing catalytic enantioselective cross-dehydrogenative coupling of cyclic amines predominantly focused on reactive N-aryl tetrahydroisoquinolines, which typically suffered from limited substrate generality and synthetic utility, and required the use of metal catalyst. Herein, a metal-free catalytic enantioselective cross-dehydrogenative coupling of N-carbamoyl cyclic amines and aldehydes has been reported for the first time. Employing an easily installed and functionalized acyl protecting group rather than the widely adopted aryl moiety endows the enantioselective process with better substrate generality and broader synthetic utility.


Influence of prenatal transportation stress on innate immune response to an endotoxin challenge in weaned Brahman bull calves†,‡.
The objective of this study was to assess the influence of prenatal stress (PNS) on innate immune responses to an endotoxin challenge in weaned bull calves. Altered innate immune response to lipopolysaccharide (LPS), as characterized by changes in a range of variables was hypothesized in PNS bull calves. Brahman cows (n = 96; 48 stressed by transportation at five stages of gestation and 48 Controls) produced 85 calves, from which 16 uncastrated male (bull) calves from each PNS and Control treatment were selected for an LPS challenge period. Rectal temperature (RT), sickness behavior score (SBS), serum concentrations of cortisol, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and complete blood count (CBC) variables were assessed in response to intravenous LPS (0.25 μg/kg body weight) administration. Each reported variable increased or decreased following LPS administration. Prior to LPS, PNS bull calves exhibited increased TNF-α, IL-6, and monocyte counts, but decreased IFN-γ, eosinophils, and basophils (p < .05). Compared with Control, in response to LPS, PNS bull calves exhibited greater circulating concentrations of cortisol. PNS bull calves exhibited lower (p < .05) eosinophil and basophil counts at time 0 (time of LPS administration) but similar counts to Control bull calves 2 h after LPS. PNS bull calves exhibited a greater change from baseline for IFN-γ and monocytes in response to LPS administration. No other variables were influenced by prenatal treatment (p > .05). These findings suggest that PNS did not adversely affect basal or induced components of the innate immune response to an immunological challenge. Lay summary Our laboratory studied the influence of prenatal stress (i.e., transportation of pregnant cows) on immune function of bull calves at 8 months of age. This was accomplished by studying aspects of their innate immune response to an immunological challenge. Prenatal stress did not adversely affect basal or induced components of the innate immune response to an immunological challenge.


Defining genes in the genome of the hyperthermophilic archaeon Pyrococcus furiosus: implications for all microbial genomes.
The original genome annotation of the hyperthermophilic archaeon Pyrococcus furiosus contained 2,065 open reading frames (ORFs). The genome was subsequently automatically annotated in two public databases by the Institute for Genomic Research (TIGR) and the National Center for Biotechnology Information (NCBI). Remarkably, more than 500 of the originally annotated ORFs differ in size in the two databases, many very significantly. For example, more than 170 of the predicted proteins differ at their N termini by more than 25 amino acids. Similar discrepancies were observed in the TIGR and NCBI databases with the other archaeal and bacterial genomes examined. In addition, the two databases contain 60 (NCBI) and 221 (TIGR) ORFs not present in the original annotation of P. furiosus. In the present study we have experimentally assessed the validity of 88 previously unannotated ORFs. Transcriptional analyses showed that 11 of 61 ORFs examined were expressed in P. furiosus when grown at either 95 or 72 degrees C. In addition, 7 of 54 ORFs examined yielded heat-stable recombinant proteins when they were expressed in Escherichia coli, although only one of the seven ORFs was expressed in P. furiosus under the growth conditions tested. It is concluded that the P. furiosus genome contains at least 17 ORFs not previously recognized in the original annotation. This study serves to highlight the discrepancies in the public databases and the problems of accurately defining the number and sizes of ORFs within any microbial genome.


Suppression of the dwarf phenotype of an Arabidopsis mutant defective in thermospermine biosynthesis by a synonymous codon change in the SAC51 uORF.
Thermospermine plays a critical role in negatively regulating xylem development in angiosperms. A mutant of Arabidopsis thaliana that is defective in thermospermine biosynthesis, acaulis5 (acl5), exhibits a dwarf phenotype with excessive xylem formation. Mechanistically thermospermine acts in attenuating the inhibitory effect of an evolutionarily conserved upstream open reading frame (uORF) on the main ORF of SAC51, which encodes a basic helix-loop-helix protein involved in xylem repression. Here, we revealed that a semidominant suppressor of acl5, sac503, which partially restores the acl5 phenotype, has a point mutation in the conserved uORF of SAC51 with no amino acid substitution in the deduced peptide sequence. In transgenic lines carrying the β-glucuronidase (GUS) reporter gene fused with the SAC51 5' region containing the uORF, the mutant construct was shown to confer higher GUS activity than does the wild-type SAC51 construct. We confirmed that sac503 mRNA was more stable than SAC51 mRNA in acl5. These results suggest that the single-base change in sac503 positively affects the translation of its main ORF instead of thermospermine. We further found that the uORF-GUS fusion protein could be synthesized in planta from the wild-type and sac503 translational fusion constructs.


Molecular and cellular impact of Psoriasin (S100A7) on the healing of human wounds.
Psoriasin, which is also known as S100A7, is a member of the S100 protein family, a group of calcium-responsive signalling proteins. Psoriasin expression remains high in patients with psoriasis, whereas it is downregulated in patients with invasive breast carcinoma. This observation suggests that this protein may be a notable marker of keratinocyte function and differentiation during wound healing. The aim of the present study was to determine the cellular impact of Psoriasin in keratinocytes, which are the primary cell type associated with wound healing. Psoriasin expression in wound tissues was examined using reverse transcription-quantitative polymerase chain reaction and immunochemical staining. Knockdown of Psoriasin in HaCaT cells was performed using anti-Psoriasin ribozyme transgenes and the effect on growth, adhesion and migration of keratinocytes was subsequently determined using in vitro cellular functional assays. Psoriasin expression is upregulated in wounds, particularly at the wound edges. The present study demonstrated that Psoriasin is expressed in keratinocytes and is a fundamental regulator of keratinocyte migration. Significant increases in the rate of keratinocyte adhesion, migration and growth were observed in Psoriasin-deficient cells (P<0.01 vs. control). Application of small inhibitors identified the potential association of neural Wiskott-Aldrich syndrome protein, focal adhesion primase and rho-associated protein kinase signalling pathways with Psoriasin-regulated cell adhesion and motility. In conclusion, Psoriasin serves an important role in the wound healing process, suggesting that it may be utilized as a potential wound healing biomarker.


Differences in Oral Structure and Tissue Interactions during Mouse vs. Human Palatogenesis: Implications for the Translation of Findings from Mice.
Clefting of the secondary palate is one of the most common human birth defects and results from failure of the palatal shelves to fuse during embryonic development. Palatogenesis is traditionally considered to be a highly conserved developmental process among mammalian species. However, cleft palate phenotypes in humans are considerably more variable than those seen in mice, the most common animal model for studying palatal development and pathogenesis of cleft palate. In this investigation, we utilized macroscopic observations, histology and 3D imaging techniques to directly compare palate morphology and the oral-nasal cavity during palate closure in mouse embryos and human conceptuses. We showed that mouse and human palates display distinct morphologies attributable to the structural differences of the oral-nasal cavity. We further showed that the palatal shelves interact differently with the primary palate and nasal septum in the hard palate region and with pharyngeal walls in the soft palate region during palate closure in mice and humans. Knowledge of these morphological differences is important for improved translation of findings in mouse models of human cleft lip/palate and, as such, should ultimately enhance our understanding of human palatal morphogenesis and the pathogenesis of cleft lip/palate in humans.


Performance of the universal portable anesthesia complete vaporizer with mechanical ventilation in both drawover and pushover configurations.
Currently, a mechanical ventilator that can be adapted to the Universal Portable Anesthesia Complete (UPAC) vaporizer and anesthetic delivery system does not exist. The need for the anesthetist to concentrate on drug delivery and fluid resuscitation for the combat casualty in the field setting provides an expedient for the adaptation of a ventilator to the UPAC system. The purpose of this study was to determine whether the performance of the UPAC vaporizer was significantly altered when mechanical ventilation was provided in a drawover versus a pushover configuration, and to provide vaporizer performance curves for ventilatory parameters common for mechanical ventilation. The Ohio V5A and Lifecare PLV-100 ventilators were used in controlled benchwork analysis. The results of the comparison between the two ventilators indicated that there was no significant difference in vaporizer output between drawover and pushover configurations. The data indicated that vaporizer output could be reliably predicted in either mode and was correlated with tidal volume and respiratory rate.


Attainment of highly uniform solid drug dispersions employing molecular scale drug entrapment in polymeric latices.
The uniformity of distribution attainable for an amine drug in solid dispersions prepared using a molecular scale entrapment procedure was investigated. Excellent reproducibility of drug content throughout the entire entrapment product was demonstrated in both flocculated (high drug levels) and deflocculated (low drug levels) systems. Drug content and content uniformity were found to be predictable for deflocculated systems, even at high drug dilution ratios. Milling or particle-size fractionation appeared to have no effect on the distribution of drug throughout the solid dispersion entrapment products. Dry blending was inferior to molecular scale drug entrapment in distributing small quantities of drug uniformly.


Adopting the International Consensus on ANA Patterns (ICAP) classification for reporting: the experience of Italian clinical laboratories.
The indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) is still considered the reference method to detect anti-nuclear antibodies (ANA) because of its high sensitivity and represents a relevant tool for the diagnosis of autoimmune rheumatic diseases. During the last decade, the International Consensus on ANA Patterns (ICAP) initiative promoted harmonization and understanding of HEp-2 IFA staining pattern nomenclature, as well as promoting their use in patient care by providing interpretation for HEp-2 IFA test results. In conjunction with a nationwide survey on the evolution of autoantibody diagnostics in autoimmune rheumatic diseases, we focused on the adherence of the Italian laboratories to the ICAP nomenclature analyzing its lights and shadows. The recent ICAP-oriented report, largely used today among Italian laboratories, also represents a further step in harmonizing and improving communication with the clinicians, adding value to laboratory findings and helping with critical clinical decisions.


Podocyte process effacement in vivo.
Foot process effacement is the most characteristic change in podocyte structure under a wide variety of human and experimental glomerulopathies with heavy proteinuria. It consists of simplification and even total disappearance of the interdigitating foot process pattern, resulting in the formation of a diffuse cytoplasmic sheet along the glomerular basement membrane. Although abundant evidence related to structural changes in podocyte foot processes has been reported, cellular or molecular mechanisms that occur within podocytes during the development of foot process effacement remain unclear. This review summarizes recent advances concerning structural and functional aspects of foot process effacement in vivo. Following a description of the general morphology of foot process effacement, the role of the cytoskeleton and its related proteins in the effacement are discussed. Finally, the relevance of foot process effacement in glomerular function is considered.


Synthesis, biodistribution, and microsingle photon emission computed tomography (SPECT) imaging study of technetium-99m labeled PEGylated dendrimer poly(amidoamine) (PAMAM)-folic acid conjugates.
Three conjugates based on dendrimer PAMAM generation five were synthesized and radiolabeled successfully. To investigate their tumor targeting, the in vitro and in vivo stability, cell uptake, in vivo biodistribution, and micro-SPECT imaging were evaluated, respectively. The conjugate of (99m)Tc labeled PEGylated dendrimer PAMAM folic acid conjugate ((99m)Tc-G5-Ac-pegFA-DTPA) shows much higher uptake in KB cancer cells and accumulated more in the tumor area than that of the other two conjugates. The uptake in KB cells depends on the incubation time. The results of in vivo biodistribution agree with the data obtained from micro-SPECT imaging. These studies show that PEGylation of PAMAM dendrimer folic acid conjugate improves the tumor targeting. Folate-conjugated dendrimer maybe developed to be potential radiopharmaceuticals and targeted drug delivery systems.


Nail neoplasms.
Nail neoplasms include all tumors occurring in the nail or periungual apparatus tissue. While some nail tumors can be similar to tumors located on the skin, others are unique. Both benign and malignant lesions can affect the nail apparatus. In particular, early malignant tumors like melanoma and squamous cell carcinoma can present similarly to onychomycosis or benign melanonychia and frequently missed by clinicians. Therefore, physicians should be aware of nail structures and the characteristics of nail tumors. Our review covers the normal nail structure and the most common nail tumors from benign to malignant.


Moderate endurance and muscle training is beneficial and safe in patients with quiescent or mildly active Crohn's disease.
Physical activity is beneficial in several chronic disorders including Crohn's disease, but the preferred type of exercise is unknown. Our study aimed to examine and compare the safety, feasibility and potential beneficial effects of individual moderate endurance and moderate muscle training in patients with Crohn's disease. Quiescent or mildly active (Crohn's disease activity index <220) patients with Crohn's disease were randomly allocated to either a control, endurance, or muscle training group. Participants exercised individually for 3 months three times per week. Endpoints included dropout rate, disease activity, inflammatory parameters including faecal calprotectin, anthropometric data, quality of life, physical activity and strength. A total of 45 patients with Crohn's disease were randomly allocated. In the endurance group (n = 17), the dropout rate was significantly higher (47% vs. 13%) compared with the muscle group (n = 15). In both groups the maximal and average strength in the upper and lower extremities increased significantly (all P < 0.04). In the endurance group emotional function was significantly improved (P = 0.03). Statistically significant changes of disease activity and other outcome parameters were not observed in this pilot cohort. Both individual moderate endurance and muscle training can be safely performed in patients with mild or quiescent Crohn's disease. Muscle training appears more feasible and may be favoured. Both forms of exercise have beneficial effects on strength. Quality of life increased in both intervention groups, although statistical significance was only reached in one subgroup.


Evaluation and Comparison of the Geometrical Relationship of Tooth and Lip Arcs and Their Correlation to Smile Arcs Between Males and Females in a North Indian Population.
Background With the increasing influence of social media, millennials and the generations that follow have increasingly pressing aesthetic concerns. Following this, there has been a sea change in treatment plans and procedures as well as the choice of material. Dentistry nowadays is dependent on digital data to compute and design prostheses; these technologies are often not readily available all over the world. The purpose of this research article is to measure the tooth arc (TA) and lip arc (LA) and their correlation to the smile arcs with a cohort consisting of males and females from a single center in northern India. The SA measurement, evaluation, and comparison of smile aesthetics in this young population may be used as a threshold to these smile variables so that prosthodontists can easily prevent or modify aesthetically displeasing features. This research article will be useful for cases requiring restorations and replacements of maxillary anterior teeth. Materials and methods In this research work, photographic analysis was used and photographs of hundred subjects were taken. The camera was fixed using a tripod, at an 11-inch distance from the face, so that a clear picture of the face could be taken from the tip of the nose to the chin. A digital single-lens reflex (DSLR) camera (Nikon D-60, with the Nikon DX AF-S Nikkor 18- 135mm lens, Tokyo, Japan) was used to take the facial photographs. As the posed smile is more predictable than the natural smile, subjects were asked to smile while keeping their natural head position (NHP). Parabolas were made with Math-GV software () and superimposed on the photographs to calculate the value. Results The mean LA shows greater curvature in the female population. There was no significant (p=0.92) relationship between TA curvature in the male (0.07±0.03) and female populations (0.08 ± 0.03), whereas the LA in males (0.10±0.03) and LA in females (0.12±0.04) showed a significant relationship (p=0.03) between both groups. The LA of the female population was found to be steeper than that of the male population. This study signifies that there is no significant difference (p=0.92) between the skeletal makeup of the male and female populations but the muscular activity and muscle function differ in the male and female populations. Regarding arc-wise comparisons in both male and female populations, the male population showed a statistically insignificant (p=0.27) correlation in lip and tooth arcs. But in the female population, the correlation between these arcs was statistically significant (p=0.01). Conclusion These study results provide useful guidance for evaluating anterior teeth and planning treatment for aesthetic restorative care. Clinicians should consider not only racial and gender differences when developing an aesthetic treatment plan but also the symmetry of the facial structure which should be in harmony with the dental arc. The harmony of each determinant of aesthetics, with each other, aids in promoting beauty as a whole.


Nicotine and cotinine concentrations in serum and milk of nursing smokers.
Analysis of 44 milk samples from 23 nursing smokers revealed that there was a linear correlation between nicotine concentrations in serum and in milk (r = 0.70). The nicotine concentrations in milk were considerably higher than the corresponding serum concentrations: milk/serum concentration ratio = 2.92 +/- 1.09; (n = 44). There was also a linear correlation between the cotinine concentrations in serum and in milk (r = 0.89). The cotinine concentrations in milk were lower than the corresponding serum concentrations: milk/serum concentration ratio = 0.78 +/- 0.19; (n = 44). The direct comparison between the half-lives of nicotine in serum and in milk was possible in five nursing smokers. The half-life of nicotine in milk was determined in four additional smoking mothers. The half-life of nicotine in milk t 1/2 = 97 +/- 20 min slightly exceeded the half-life of nicotine in serum t 1/2 = 81 +/- 9 min; the difference between these two values was not statistically significant (P greater than 0.05). Cotinine concentrations remained fairly consistent during a 4 h interval without smoking.


The relationship between obstetrical interventions and the increase in U.S. preterm births, 2014-2019.
We examined the relationship between obstetrical intervention and preterm birth in the United States between 2014 and 2019. This observational study analyzed 2014-2019 US birth data to assess changes in preterm birth, cesarean delivery, induction of labor, and associated risks. Logistic regression modeled the odds of preterm obstetrical intervention (no labor cesarean or induction) after risk adjustment. The percentage of singleton preterm births in the United States increased by 9.4% from 2014-2019. The percent of singleton, preterm births delivered by cesarean increased by 6.0%, while the percent with induction of labor increased by 39.1%. The percentage of singleton preterm births where obstetrical intervention (no labor cesarean or induction) potentially impacted the gestational age at delivery increased from 47.6% in 2014 to 54.9% in 2019. Preterm interventions were 13% more likely overall in 2019 compared to 2014 and 17% more likely among late preterm births, after controlling for demographic and medical risk factors. Compared to non-Hispanic White women, Non-Hispanic Black women had a higher risk of preterm obstetric interventions. Preterm infants have higher morbidity and mortality rates than term infants, thus any increase in the preterm birth rate is concerning. A renewed effort to understand the trends in preterm interventions is needed to ensure that obstetrical interventions are evidence-based and are limited to those cases where they optimize outcomes for both mothers and babies.


Microwave-assisted synthesis of HYNIC protected analogue for 99mTc labeled antibody.
We described herein a simple and efficient microwave assisted synthesis of HYNIC analogues. Two different activated esters of HYNIC, the hydrazine protected with a trifluoroacetyl group (5) and the free hydrazine (6) were conjugated to the monoclonal antibody Nimotuzumab. Technetium-99m radiolabeling of Nimotuzumab was achieved with high efficiency using 5 and 6 derivates. The NHS-HYNIC-Tfa derivate allowed better labeling yields during longer times of preservation of the conjugated antibody.


Freezing-Enhanced Dissolution of Iron Oxides: Effects of Inorganic Acid Anions.
Dissolution of iron from mineral dust particles greatly depends upon the type and amount of copresent inorganic anions. In this study, we investigated the roles of sulfate, chloride, nitrate, and perchlorate on the dissolution of maghemite and lepidocrocite in ice under both dark and UV irradiation and compared the results with those of their aqueous counterparts. After 96 h of reaction, the total dissolved iron in ice (pH 3 before freezing) was higher than that in the aqueous phase (pH 3) by 6-28 times and 10-20 times under dark and UV irradiation, respectively. Sulfuric acid was the most efficient in producing labile iron under dark condition, whereas hydrochloric acid induced the most dissolution of the total and ferrous iron in the presence of light. This ice-induced dissolution result was also confirmed with Arizona Test Dust (AZTD). In the freeze-thaw cycling test, the iron oxide samples containing chloride, nitrate, or perchlorate showed a similar extent of total dissolved iron after each cycling while the sulfate-containing sample rapidly lost its dissolution activity with repeating the cycle. This unique phenomenon observed in ice might be related to the freeze concentration of protons, iron oxides, and inorganic anions in the liquid-like ice grain boundary region. These results suggest that the ice-enhanced dissolution of iron oxides can be a potential source of bioavailable iron, and the acid anions critically influence this process.


Characterizing light-dark cycles in the Neonatal Intensive Care Unit: a retrospective observational study.
Objectives: To characterize bedside 24-h patterns in light exposure in the Neonatal Intensive Care Unit (NICU) and to explore the environmental and individual patient characteristics that influence these patterns in this clinical setting. Methods: We conducted a retrospective cohort study that included 79 very preterm infants who stayed in an incubator with a built-in light sensor. Bedside light exposure was measured continuously (one value per minute). Based on these data, various metrics (including relative amplitude, intradaily variability, and interdaily stability) were calculated to characterize the 24-h patterns of light exposure. Next, we determined the association between these metrics and various environmental and individual patient characteristics. Results: A 24-h light-dark cycle was apparent in the NICU with significant differences in light exposure between the three nurse shifts (p < 0.001), with the highest values in the morning and the lowest values at night. Light exposure was generally low, with illuminances rarely surpassing 75 lux, and highly variable between patients and across days within a single patient. Furthermore, the season of birth and phototherapy had a significant effect on 24-h light-dark cycles, whereas no effect of bed location and illness severity were observed. Conclusion: Even without an official lighting regime set, a 24-h light-dark cycle was observed in the NICU. Various rhythmicity metrics can be used to characterize 24-h light-dark cycles in a clinical setting and to study the relationship between light patterns and health outcomes.


Mutational analysis of class A and class B penicillin-binding proteins in Streptococcus gordonii.
High-molecular-weight (HMW) penicillin-binding proteins (PBPs) are divided into class A and class B PBPs, which are bifunctional transpeptidases/transglycosylases and monofunctional transpeptidases, respectively. We determined the sequences for the HMW PBP genes of Streptococcus gordonii, a gingivo-dental commensal related to Streptococcus pneumoniae. Five HMW PBPs were identified, including three class A (PBPs 1A, 1B, and 2A) and two class B (PBPs 2B and 2X) PBPs, by homology with those of S. pneumoniae and by radiolabeling with [3H]penicillin. Single and double deletions of each of them were achieved by allelic replacement. All could be deleted, except for PBP 2X, which was essential. Morphological alterations occurred after deletion of PBP 1A (lozenge shape), PBP 2A (separation defect and chaining), and PBP 2B (aberrant septation and premature lysis) but not PBP 1B. The muropeptide cross-link patterns remained similar in all strains, indicating that cross-linkage for one missing PBP could be replaced by others. However, PBP 1A mutants presented shorter glycan chains (by 30%) and a relative decrease (25%) in one monomer stem peptide. Growth rate and viability under aeration, hyperosmolarity, and penicillin exposure were affected primarily in PBP 2B-deleted mutants. In contrast, chain-forming PBP 2A-deleted mutants withstood better aeration, probably because they formed clusters that impaired oxygen diffusion. Double deletion could be generated with any PBP combination and resulted in more-altered mutants. Thus, single deletion of four of the five HMW genes had a detectable effect on the bacterial morphology and/or physiology, and only PBP 1B seemed redundant a priori.


Telomeres, aging, and plants: from weeds to Methuselah - a mini-review.
The process of aging affects most, if not all, living creatures, from single celled yeast to multi-cellular mammals and plants. The DNA end-replication problem along with the tissue-limited expression of telomerase led to the telomere hypothesis of aging, where limits on cellular proliferation are genetically encoded in the lengths of a cell's telomeres. Support for this hypothesis has been found in several organisms, from worms to mice to humans. While development, and therefore the process of aging, is quite different between plants and animals, telomere biology between these organisms is fundamentally the same. Do telomeres, then, also play the role of a molecular clock in plants? In this review, we explore the current knowledge of the relationship between telomeres and aging in plants in three specific cases: leaf senescence, aging of perennials and seed longevity.


Expression of p-AMPK in colorectal cancer revealed substantial diverse survival patterns.
Several cancers have showed differences in the role of p- AMPK in cancer growth, progression and prognosis, and little is identified regarding the significance of p-AMPK expression in colorectal adenocarcinoma. Therefore, this report will define p-AMPK phenotype in a panel of colorectal carcinomas and explore the relationship between this phenotype and tumor clinicopathological features. A total of 228 cases comprising 155 large intestine cancers and 73 controls (40 benign tumors and thirty three non-cancerous tissues) were employed in tissue microarray construction. Immunohistochemistry (IHC) staining was applied to reveal p-AMPK expression. This study was carried out in the pathology lab of King Abdulaziz University Hospital over a duration of 15 months and was completed on 7th July 2018. Phosphorylated AMPK was identified in 133 (85.8%) of colorectal cancers and 73 (100%) control cases. Histologic type was noticeably correlated with p-AMPK immunostaining (P= 0.001), high score of p-AMPK immunostaining is more frequent in control cases. Considerable varied survival models were observed with neoplasm size, metastatic tumor, recurrence and disease relapse (P-values<0.01). Survival estimates are considerably healthier in positive cases which have one of the following features size less than 5 cm, absence of metastatic tumor, no reoccurrence or disease relapse. The present study showed a reduction in the IHC staining of p-AMPK in colorectal cancer compared with controls. IHC staining of p-AMPK can be a supportive marker in predicting prognosis and survival estimates of colorectal tumors with specific clinical factors.


Rapid prototyping composite and complex scaffolds with PAM2.
To create composite synthetic scaffolds with the same degree of complexity and multilevel organization as biological tissue, we need to integrate multilevel biomaterial processing in rapid prototyping systems. The scaffolds then encompass the entire range of properties, which characterize biological tissue. A multilevel microfabrication system, PAM(2), has been developed to address this gap in material processing. It is equipped with different modules, each covering a range of material properties and spatial resolutions. Together, the modules in PAM(2) can be used to realize complex and composite scaffolds for tissue engineering, bringing us a step closer to real clinical applications. This chapter describes the PAM(2) system and discusses some of the practical issues associated with scaffold microfabrication and biomaterial processing.


A High-Resolution MRI Study of Relationship between Remodeling Patterns and Ischemic Stroke in Patients with Atherosclerotic Middle Cerebral Artery Stenosis.
Purpose: Recently, high-resolution magnetic resonance imaging (HR-MRI) has been used to depict the wall characteristics of the intracranial arteries. The aim of this study was to explain the relationship between the remodeling patterns and acute ischemic stroke in patients with atherosclerotic middle cerebral artery (MCA) stenosis using HR-MRI. Materials and Methods: From August 2015 to May 2016, we prospectively screened 33 consecutive patients with unilateral MCA stenosis using time-to-flight MR angiography, including 15 patients with symptomatic MCA stenosis and 18 patients with asymptomatic MCA stenosis. Among them, 14 patients were diagnosed as positive remodeling (PR) and 19 as negative remodeling or non-remodeling. The cross-sectional images of the stenotic MCA wall on HR-MRI including T1WI, T2WI, and PDWI were compared between the symptomatic group and the asymptomatic group as well as the PR group and the non-PR group, based on the vessel area, lumen area, wall area, plaque area, degree of stenosis, remodeling index, and NIHSS score. Results: The symptomatic group had larger wall area (P = 0.040), plaque area (P<0.001), degree of stenosis (P = 0.038), remodeling index (P < 0.001), and NIHSS score (P = 0.003) as well as smaller lumen area (P = 0.001) than the asymptomatic group. In addition, more PR patients were observed in symptomatic group. The PR group had larger plaque area (P = 0.014) and NIHSS score (P = 0.037) than the non-PR group. Demographic and clinical characteristics between the symptomatic group and the asymptomatic group, the PR group and the non-PR group showed no statistical difference. Conclusion: The current study suggests that the HR-MRI has emerged as a promising tool to detect the characteristics of intracranial arteries wall and reveal the relationship between remodeling patterns and ischemic stroke. The PR is an unsafe remodeling way and is prone to cause acute ischemic stroke.


HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers.
Tissue hypoxia commonly occurs in tumors. Hypoxia- inducible factor (HIF)-1 and HIF-2, which are essential mediators of cellular response to hypoxia, regulate gene expression for tumor angiogenesis, glucose metabolism, and resistance to oxidative stress. Their key regulatory subunits, HIF1A (HIF-1alpha) and endothelial PAS domain protein 1 (EPAS1; HIF-2alpha), are overexpressed and associated with patient prognosis in a variety of cancers. However, prognostic or molecular features of colon cancer with HIF expression remain uncertain. Among 731 colorectal cancers in two prospective cohort studies, 142 (19%) tumors showed HIF1A overexpression, and 322 (46%) showed EPAS1 overexpression by immunohistochemistry. HIF1A overexpression was significantly associated with higher colorectal cancer-specific mortality in Kaplan-Meier analysis (log-rank test, P < 0.0001), univariate Cox regression (hazard ratio = 1.84; 95% confidence interval, 1.37 to 2.47; P < 0.0001) and multivariate analysis (adjusted hazard ratio = 1.72; 95% confidence interval, 1.26 to 2.36; P = 0.0007) that adjusted for clinical and tumoral features, including microsatellite instability, TP53 (p53), PTGS2 (cyclooxygenase-2), CpG island methylator phenotype, and KRAS, BRAF, PIK3CA, and LINE-1 methylation. In contrast, EPAS1 expression was not significantly associated with patient survival. In addition, HIF1A expression was independently associated with PTGS2 expression (P = 0.0035), CpG island methylator phenotype-high (P = 0.013), and LINE-1 hypomethylation (P = 0.017). EPAS1 expression was inversely associated with high tumor grade (P = 0.0017) and obesity (body mass index > or = 30 kg/m2) (P = 0.039). In conclusion, HIF1A expression is independently associated with poor prognosis in colorectal cancer, suggesting HIF1A as a biomarker with potentially important therapeutic implications.


Predicting financial losses due to apartment construction accidents utilizing deep learning techniques.
This study aims to generate a deep learning algorithm-based model for quantitative prediction of financial losses due to accidents occurring at apartment construction sites. Recently, the construction of apartment buildings is rapidly increasing to solve housing shortage caused by increasing urban density. However, high-rise and large-scale construction projects are increasing the frequency and severity of accidents occurring inside and outside of construction sites, leading to increases of financial losses. In particular, the increase in severe weather and the surge in abnormal weather events due to climate change are aggravating the risk of financial losses associated with accidents occurring at construction sites. Therefore, for sustainable and efficient management of construction projects, a loss prediction model that prevents and reduces the risk of financial loss is essential. This study collected and analyzed insurance claim payout data from a main insurance company in South Korea regarding accidents occurring inside and outside of construction sites. Deep learning algorithms were applied to develop predictive models reflecting scientific and recent technologies. Results and framework of this study provide critical guidance on financial loss management necessary for sustainable and efficacious construction project management. They can be used as a reference for various other construction project management studies.


Performance of the anaerobic baffled reactor under steady-state and shock loading conditions.
The anaerobic baffled reactor (ABR) contains a granulated, mixed anaerobic culture segregated into compartments. Operation of four reactors under a range of hydraulic retention times showed that this novel reactor design offers highly efficient performance in the conversion of carbon in the feed stream to methane and carbon dioxide. The design parameter varied was the number of compartments. COD removal at 20 h retention time was routinely over 95% in all reactors, with low washout of biomass. Very high specific reaction rates were achievable (although with a loss of efficiency) at low biomass concentrations and high loading rates. In order to optimize volumetric reaction rates, a tradeoff has to be made between high biomass concentration, granule size, and the resulting mass transfer limitations. Formate is shown to be an important intermediate in the process under conditions of high loading.


A novel workflow correlating RNA-seq data to Phythophthora infestans resistance levels in wild Solanum species and potato clones.
Comparative transcriptomics between species can provide valuable understanding of plant-pathogen interactions. Here, we focus on wild Solanum species and potato clones with varying degree of resistance against Phytophthora infestans, which causes the devastating late blight disease in potato. The transcriptomes of three wild Solanum species native to Southern Sweden, Solanum dulcamara, Solanum nigrum, and Solanum physalifolium were compared to three potato clones, Desiree (cv.), SW93-1015 and Sarpo Mira. Desiree and S. physalifolium are susceptible to P. infestans whereas the other four have different degrees of resistance. By building transcript families based on de novo assembled RNA-seq across species and clones and correlating these to resistance phenotypes, we created a novel workflow to identify families with expanded or depleted number of transcripts in relation to the P. infestans resistance level. Analysis was facilitated by inferring functional annotations based on the family structure and semantic clustering. More transcript families were expanded in the resistant clones and species and the enriched functions of these were associated to expected gene ontology (GO) terms for resistance mechanisms such as hypersensitive response, host programmed cell death and endopeptidase activity. However, a number of unexpected functions and transcripts were also identified, for example transmembrane transport and protein acylation expanded in the susceptible group and a cluster of Zinc knuckle family proteins expanded in the resistant group. Over 400 expressed putative resistance (R-)genes were identified and resistant clones Sarpo Mira and SW93-1015 had ca 25% more expressed putative R-genes than susceptible cultivar Desiree. However, no differences in numbers of susceptibility (S-)gene homologs were seen between species and clones. In addition, we identified P. infestans transcripts including effectors in the early stages of P. infestans-Solanum interactions.


Topological dynamics of holins in programmed bacterial lysis.
The fate of phage-infected bacteria is determined by the holin, a small membrane protein that triggers to disrupt the membrane at a programmed time, allowing a lysozyme to attack the cell wall. S(21)68, the holin of phage 21, has two transmembrane domains (TMDs) with a predicted N-in, C-in topology. Surprisingly, TMD1 of S(21)68 was found to be dispensable for function, to behave as a SAR ("signal-anchor-release") domain in exiting the membrane to the periplasm, and to engage in homotypic interactions in the soluble phase. The departure of TMD1 from the bilayer coincides with the lethal triggering of the holin and is accelerated by membrane depolarization. Basic residues added at the N terminus of S(21)68 prevent the escape of TMD1 to the periplasm and block hole formation by TMD2. Lysis thus depends on dynamic topology, in that removal of the inhibitory TMD1 from the bilayer frees TMD2 for programmed formation of lethal membrane lesions.


Laparoscopy Combined With Transanal Endoscopic Microsurgery for Rectal Cancer: A Prospective, Single-blinded, Randomized Clinical Trial.
To evaluate the efficacy of laparoscopy combined with transanal endoscopic microsurgery (TEM) in the treatment of rectal cancer. A total of 60 rectal cancer patients who underwent radical resection from December 2009 to December 2013 were enrolled in this study. All patients were randomly divided to receive either laparoscopic surgery (LA group) or laparoscopy combined with TEM (LT group). Demographics including age and sex, and tumor characteristics including tumor size, distance from anal verge, and preoperative staging were all recorded. The operation time, hospital stay, cases with intraoperative blood transfusion, the number of resected lymph node, postoperative out-of-bed activity, passage of gas by anus, fasting time, and postoperative complications were assessed. Compared with the LA group, patients in the LT group had shorter operation time (118.5±22.0 vs. 138.1±23.8 min, P=0.002), earlier out-of-bed activity (60.4±19.2 vs. 83.6±9.6 h, P=0.001) and passage of gas by anus (81.4±5.4 vs. 86.2±8.7 h, P=0.013), and shorter hospital stay (8.0±2.8 vs. 11.0±3.5 d, P=0.001). Patients were followed up for a median time of 28 months (range, 3 to 48 mo). No local recurrence and distant metastasis occurred in all cases. Laparoscopy combined with TEM is a feasible and effective treatment for radical excision of middle-upper rectal cancer due to the advantages of lower morbidity and earlier recovery.


Protective effect of gastrin-releasing peptide receptor antagonist in carrageenan-induced pleural inflammation in rats.
We report the effects of the gastrin-releasing peptide (GRP) receptor antagonist RC-3095 in an acute inflammation model induced by carrageenan. Male Wistar rats received saline or saline containing 2% lambda-carrageenan into the pleural cavity, with some also receiving RC-3095 3 mg/kg subcutaneously, immediately after surgery. Four hours later, the rats were killed and pleural exudate was obtained for evaluation of total cell count, lactate dehydrogenase activity, total protein, cytokines analysis and nitrite/nitrate concentrations; myeloperoxidase (MPO) activity and oxidative stress were evaluated in the lung. RC-3095 exhibited pronounced anti-inflammatory actions by inhibition of leukocyte influx and blockade of MPO, nitrite/nitrate and cytokine levels. Moreover, the results showed that RC-3095 elicits action against oxidative damage in lipids and proteins, as well as increasing cell viability. The present findings suggest that GRP plays a role in acute inflammation that can be related with the reduction of oxidative damage and that it could be effective in therapeutic applications.


The effect of time of day of insemination and oviposition on the fertility of turkey hens.
Turkey hens were inseminated at five different times of the day to determine the effect of time of day of insemination and the stage of egg formation on fertility. Results showed that fertility resulting from the 6 p.m. insemination was significantly greater than at 8 a.m., 10 a.m., 1 p.m. or 3 p.m. Conversely, fertility was significantly lower at 1 p.m. than at the other four times. Fertility was significantly lower if hens were inseminated during the last 10 hours that the egg was in the uterus and during the approximate time of ovulation than during the other times of egg development.


Validation of Visual Prostate Symptom Score (VPSS) in Brazilian Sample Population.
The aim of the study was to evaluate the reliability and validity of the Visual Prostate Symptom Score (VPSS), its correlation with the International Prostate Symptom Score (IPSS), and the time required and need for help when completing the instrument. We also aimed to identify variables associated with difficulty completing these instruments. Longitudinal, prospective correlational study. The target population was Brazilian men from different cities within the state of São Paulo with lower urinary tract symptoms followed in urological consultation at a university hospital during October 2017. The sample comprised 59 patients with a mean age of 66.53 years. Reliability of the VPSS was evaluated using a test-retest approach and its convergent validity with the IPSS. Cronbach α coefficient was also calculated. Both questionnaires were self-administered and, in case of difficulty of comprehension, assistance was provided. Mean completion time of the IPSS was 6.56 minutes and for VPSS was 5.02 minutes. The variables skin color and educational level were associated with the difficulty in completing the IPSS and for comprehending meaning of the VPSS pictograms. Internal consistency evaluated using Cronbach α coefficient was 0.74 for IPSS and 0.15 for VPSS, respectively. Test-retest reliability testing revealed that both instruments had a high intraclass correlation index (>0.75). There was a significant correlation between the health-related quality of life (QoL) scores of the 2 instruments (0.71, P = .0001) and between the total score of each instrument with its corresponding QoL score. Although time for response of the VPSS was shorter and it demonstrated good test-retest reliability, it more frequently required help to answer. The VPSS showed low internal consistency and low correlation with the IPSS (except for the QoL item).


Statistics in diagnostic medicine.
This tutorial gives an introduction into statistical methods for diagnostic medicine. The validity of a diagnostic test can be assessed using sensitivity and specificity which are defined for a binary diagnostic test with known reference or gold standard. As an example we use Procalcitonin with a cut off value ≥ 0.5 g/L as a test and Sepsis-2 criteria as a reference standard for the diagnosis of sepsis. Next likelihood ratios are introduced which combine the information given by sensitivity and specificity. For these measures the construction of confidence intervals is demonstrated. Then, we introduce predictive values using Bayes' theorem. Predictive values are sometimes difficult to communicate. This can be improved using natural frequencies which are applied to our example. Procalcitonin is actually a continuous biomarker, hence we introduce the use of receiver operator curves (ROC) and the area under the curve (AUC). Finally we discuss sample size estimation for diagnostic studies. In order to show how to apply these concepts in practice we explain how to use the freely available software R.


Analysis of a partially observed binary covariate process and a censored failure time in the presence of truncation and competing risks.
We develop methods for assessing the association between a binary time-dependent covariate process and a failure time endpoint when the former is observed only at a single time point and the latter is right censored, and when the observations are subject to truncation and competing causes of failure. Using a proportional hazards model for the effect of the covariate process on the failure time of interest, we develop an approach utilizing EM algorithm and profile likelihood for estimating the relative risk parameter and cause-specific hazards for failure. The methods are extended to account for other covariates that can influence the time-dependent covariate process and cause-specific risks of failure. We illustrate the methods with data from a recent study on the association between loss of hepatitis B e antigen and the development of hepatocellular carcinoma in a population of chronic carriers of hepatitis B.


Identification of genomic regions associated with early plant vigour in lentil (Lens culinaris).
Lentil is one of the most important food legume species, however its genetic and genomic resources remained largely uncharacterized and unexploited. In the past few years, a number of genetic maps have been constructed and marker resources have been developed in lentil. These resources could be exploited for understanding the extent and distribution of genetic variation in genus Lens and also for developing saturated and consensus genetic maps suitable for quantitative trait loci (QTL) mapping and marker-assisted selection. The present study aims to enrich polymerase chain reaction-based linkage map of F10 recombinant inbred lines (RILs) population of 94 individuals derived from cross WA8649090 9 Precoz and identification of QTLs linked to early plant vigour traits. Of the 268 polymorphic markers (93 simple sequence repeats (SSR), three inter-simple sequence repeats (ISSRs) and 172 random amplified polymorphic DNA (RAPDs)), 265 (90 SSRs, three ISSRs and 172 RAPDs) were mapped on seven linkage groups, varying in length between 25.6 and 210.3 cM, coverage of 809.4 cM with an average marker spacing of 3.05 cM. The study also reported assigning of 24 new cross-genera SSRs of Trifolium pratense on the present linkage map. The RILs along with the parents were screened for shoot length, root length, seedling length, dry weight, number of leaves and number of branches based on two replications under polyhouse conditions. A QTLhotspot consisting of six QTLs for shoot length (cm), root length (cm) and seedling length (cm) was observed between a map distances of56.61 and 86.81 cM on LG1.


Noninvasive Prediction of Erosive Esophagitis Using a Controlled Attenuation Parameter (CAP)-Based Risk Estimation Model.
Erosive esophagitis and fatty liver share obesity and visceral fat as common critical pathogenesis. However, the relationship between the amount of hepatic fat and the severity of erosive esophagitis was not well investigated, and there is no risk estimation model for erosive esophagitis. To evaluate the relationship between the amount of hepatic fat and the severity of erosive esophagitis and then develop a risk estimation model for erosive esophagitis. We enrolled 1045 consecutive participants (training cohort, n = 705; validation cohort, n = 340) who underwent esophagogastroduodenoscopy and CAP. The relationship between severity of fatty liver and erosive esophagitis was investigated, and independent predictors for erosive esophagitis that have been investigated through logistic regression analyses were used as components for establishing a risk estimation model. The prevalence of erosive gastritis was 10.7 %, and the severity of erosive esophagitis was positively correlated with the degree of hepatic fatty accumulation (P < 0.05). A CAP-based risk estimation model for erosive esophagitis using CAP, Body mass index, and significant alcohol Drinking as constituent variables was established and was dubbed the CBD score (AUROC = 0.819, range 0-11). The high-risk group (CBD score ≥3) showed significantly higher risk of having erosive esophagitis than the low-risk group (CBD score <3) (24.1 vs. 2.7 %, respectively; P < 0.001). The diagnostic accuracy of CBD score was maintained in the validation cohort (AUROC = 0.848). The severity of erosive esophagitis was positively correlated with the degree of hepatic fatty accumulation, and the CBD score might be a simple CAP-based risk model for predicting erosive esophagitis.


Distribution pattern of ethyl glucuronide and caffeine concentrations over the scalp of a single person in a forensic context.
The distribution of analyte concentrations in hair across the scalp has not been thoroughly investigated. Differences in concentrations depending on sampling location are problematic, especially when measuring a second strand to confirm the result of the first measurement. Aiming at a better understanding of the concentration differences, the distribution of ethyl glucuronide (EtG) and caffeine concentrations in hair across the entire head of one test subject was investigated by dividing the scalp completely into regions of ca 2 cm × 2 cm area, yielding a total of 104 samples. For the quantification of EtG, a novel LC-MS3 /MRM method was developed and validated with a limit of detection and limit of quantification of 2 and 4 pg/mg, respectively. Large variations of the concentration across the head were found, with factors of ca 3.0 and 10.6 for EtG and caffeine, respectively. These differences could not be attributed to measurement error alone. The concentrations were projected onto the subject's head, and concentration patterns were identified for EtG and caffeine. When examining multiple strands from within one 2 cm × 2 cm sampling area, the strands showed similar concentrations. Segmental analysis of selected 3 cm strands showed decreasing concentrations of EtG and caffeine from proximal to distal end, possibly due to wash-out of the analytes. Copyright © 2017 John Wiley & Sons, Ltd.


The Methanothermobacter thermautotrophicus ExoIII homologue Mth212 is a DNA uridine endonuclease.
The genome of Methanothermobacter thermautotrophicus, as a hitherto unique case, is apparently devoid of genes coding for general uracil DNA glycosylases, the universal mediators of base excision repair following hydrolytic deamination of DNA cytosine residues. We have now identified protein Mth212, a member of the ExoIII family of nucleases, as a possible initiator of DNA uracil repair in this organism. This enzyme, in addition to bearing all the enzymological hallmarks of an ExoIII homologue, is a DNA uridine endonuclease (U-endo) that nicks double-stranded DNA at the 5'-side of a 2'-d-uridine residue, irrespective of the nature of the opposing nucleotide. This type of activity has not been described before; it is absent from the ExoIII homologues of Escherichia coli, Homo sapiens and Methanosarcina mazei, all of which are equipped with uracil DNA repair glycosylases. The U-endo activity of Mth212 is served by the same catalytic center as its AP-endo activity.


[Isolation of the respiratory syncytial virus from calves with respiratory diseases].
Described is a respiratory enzootic in calves aged 30 to 90 days. Two cytopathic strains of the bovine respiratory syncytial virus were isolated from diseased calves in a cell culture of lamb thyroid. Clinical observations and the results of virologic and serologic investigations have revealed that mixed infections of the respiratory syncytial virus and the mucosa disease virus take part in the etiology of the respiratory enzootic described.


Low-level laser therapy in burning mouth syndrome patients: a pilot study.
The aim of this study was to investigate the effect of low-level laser therapy (LLLT) on the treatment of burning mouth syndrome (BMS). In addition, the laser effect was compared on the different affected oral sites. Eleven subjects with a total of 25 sites (tongue, lower lip, upper lip, and palate) affected by a burning sensation were selected. The affected areas were irradiated once a week for three consecutive weeks with an infrared laser (λ = 790 nm). The probe was kept in contact with the tissue, and the mucosal surface was scanned during the irradiation. The exposure time was calculated based on the fluence of 6 J/cm(2), the output power of 120 mW, and the area to be treated. Burning intensity was recorded through a visual analog scale before and after the treatment and at the 6-week follow-up. The percentage of the improvement in symptoms was also obtained. Burning intensity at the end of the laser therapy was statistically lower than at the beginning (p < 0.01). Patients reported an 80.4% reduction in the intensity of symptoms after laser treatment. There was no statistical difference between the end of the treatment and the 6-week follow-up, except for the tongue site. Under the investigated parameters, infrared LLLT proved to be a valuable alternative for BMS treatment, providing a significant and lasting reduction in symptoms.


Reporting of violence against children and adolescents in a protective institution in southern Brazil.
This study aimed to analyze the reports of violence against children and adolescents in the period between January 2009 and May 2014 in a municipality protection institution of Rio Grande, RS. This is a descriptive and documentary study with a quantitative approach that analyzed 800 medical records of Specialized Reference Center for Social Assistance (CREAS), from the development of a research instrument containing the study variables. The results show that 44.5% of the notifications sent to the protection of organs were carried out by family members and evidence of physical signs was the reason that triggered them (34%). The dismissing by abandonment of families is very present in the institution (36.9%), which possibly supports the maintenance of the cycle of violence. The results of this study show that although there were improvements regarding the notification by the family, the number of notifications made by the health and education sectors are still reduced, thereby increasing the need for more effective and articulated actions in these sectors.


Quantitative Analysis of Phenolic Acids and Flavonoids in Cuscuta chinensis Lam. by Synchronous Ultrasonic-Assisted Extraction with Response Surface Methodology.
An effective ultrasonic-assisted extraction method for the separation of phenolic acids and flavonoids in Cuscuta chinensis Lam. was conducted by combining uniform design (UD) coupled with response surface methodology (RSM) and orthogonal design (OD) experiment. A sensitive and selective high-performance liquid chromatography-electrospray ionization tandem triple quadrupole mass spectrometry (HPLC-ESI-MS/MS) method was applied to quantify the sixteen active ingredients (chlorogenic acid, cryptochlorogenic acid, neochlorogenic acid, isochlorogenic acid A, isochlorogenic acid B, isochlorogenic acid C, caffeic acid, hyperin, isoquercitrin, quercetin, campherol, p-coumaric acid, isorhamnetin, rutin, astragalin, and apigenin). The extraction method was optimized with respect to concentration of extraction solvent, extraction time, and ratio of liquid to solid as a consequence of getting a high sensitive and feasible method for simultaneous determination of contents of multiple components and evaluation of quality control of Cuscuta chinensis Lam. from different origins. It was also considered useful and valuable in the further study for quality control of Cuscuta chinensis Lam.


Noncrystalline-to-crystalline transformations in Pt nanoparticles.
We show that the noncrystalline-to-crystalline transition of supported Pt nanoparticles (NPs) in the subnanometer to nanometer size range is statistical in nature, and strongly affected by particle size, support, and adsorbates (here we use H2). Unlike in the bulk, a noncrystalline phase exists and is stable in small NPs, reflecting a general mesoscopic feature. Observations of >3000 particles by high-resolution transmission electron microscopy show a noncrystalline-to-crystalline transition zone that is nonabrupt; there is a size regime where disordered and ordered NPs coexist. The NP size at which this transition occurs is strongly dependent on both the adsorbate and the support, and this effect is general for late 5d transition metals. All results are reconciled via a statistical description of particle-support-adsorbate interactions.


Interaction of gentamicin sulfate with alginate and consequences on the physico-chemical properties of alginate-containing biofilms.
Alginate is one of the main extracellular polymeric substances (EPS) in biofilms of Cystic Fibrosis (CF) patients suffering from pulmonary infections. Gentamicin sulfate (GS) can strongly bind to alginate resulting in loss of pharmacological activity; however neither the mechanism nor its repercussion is fully understood. In this study, we investigated how GS modifies the alginate macromolecular network and its microenvironment. Alginate gels of two different compositions (either enriched in guluronate units (G) or enriched in mannuronate units (M)) were crosslinked with Ca2+ and exposed to GS at varying times and concentrations. The complexes formed were characterized via turbidimetry, mechanical tests, swelling assay, calorimetry techniques, nuclear magnetic resonance, Ca2+ displacement, macromolecular probe diffusion and pH alteration. In presence of GS, the alginate network and its environment undergo a tremendous reorganization in terms of gel density, stiffness, diffusion property, presence and state of the water molecules. We noted that the intensity of those alterations is directly dependent on the polysaccharide motif composition (ratio M/G). Our results underline the importance of alginate as biofilm component, its pernicious role during antibiotherapy and could represent a potential macromolecular target to improve anti-infectious therapies.


Crystallization of as-Mesocellular Silica Foam into Hierarchical TS-1 Zeolites by Conventional Hydrothermal and Dense-Gel Routes for Oxidation Reactions.
Crystallization of as-mesocellular silica foam (as-MCF) into TS-1 zeolites by conventional hydrothermal and dense-gel routes is reported. The TS-1 synthesized through the dense-gel route (TS-1-d) showed higher meso-macroporosity (0.311 vs 0.233 cm3/g), smaller particle size (130 vs 305 nm), and enhanced external surface area (86 vs 31 m2/g) than that synthesized under conventional hydrothermal conditions (TS-1-h). These might suggest that an organic template from as-MCF acted as mesoporogen in the dense-gel synthesis; however, segregation of the organic template and the synthesis mixture occurred in the conventional hydrothermal synthesis. The obtained TS-1 from the crystallization of as-MCF showed an enhanced framework Ti. The turnover frequencies (h-1) of TS-1-d toward hydroxylation of phenol and oxidation of dibenzothiophene (DBT) were 2 and 5 times, respectively, higher than those by TS-1-h. The DBT conversion by TS-1-d reached >99.0%, while it was only 63% by TS-1-h, suggesting the potential of TS-1-d for deep desulfurization of the fuels. Consequently, the crystallization of as-mesoporous materials through the dense-gel route is a promising approach to prepare TS-1 zeolites with smaller particle sizes and enhanced mesoporosity.


Green Light Exposure Elicits Anti-inflammation, Endogenous Opioid Release and Dampens Synaptic Potentiation to Relieve Post-surgical Pain.
Light therapy improves multiple conditions such as seasonal affective disorders, circadian rhythm dysregulations, and neurodegenerative diseases. However, little is known about its potential benefits in pain management. While current pharmacologic methods are effective in many cases, the associated side effects can limit their use. Non-pharmacological methods would minimize drug dependence, facilitating a reduction of the opioid burden. Green light therapy has been shown to be effective in reducing chronic pain in humans and rodents. However, its underlying mechanisms remain incompletely defined. In this study, we demonstrate that green light exposure reduced postsurgical hypersensitivity in rats. Moreover, this therapy potentiated the antinociceptive effects of morphine and ibuprofen on mechanical allodynia in male rats. Importantly, in female rats, GLED potentiated the antinociceptive effects of morphine but did not affect that of ibuprofen. We showed that green light increases endogenous opioid levels while lessening synaptic plasticity and neuroinflammation. Importantly, this study reveals new insights into how light exposure can affect neuroinflammation and plasticity in both genders. Clinical translation of these results could provide patients with improved pain control and decrease opioid consumption. Given the noninvasive nature of green light, this innovative therapy would be readily implementable in hospitals. PERSPECTIVE: This study provides a potential additional therapy to decrease postsurgical pain. Given the safety, availability, and the efficacy of green light therapy, there is a significant potential for advancing the green light therapy to clinical trials and eventual translation to clinical settings.


Robotic, laparoscopic and open surgery for gastric cancer compared on surgical, clinical and oncological outcomes: a multi-institutional chart review. A study protocol of the International study group on Minimally Invasive surgery for GASTRIc Cancer-IMIGASTRIC.
Gastric cancer represents a great challenge for healthcare providers and requires a multidisciplinary treatment approach in which surgery plays a major role. Minimally invasive surgery has been progressively developed, first with the advent of laparoscopy and recently with the spread of robotic surgery, but a number of issues are currently being debated, including the limitations in performing an effective extended lymph node dissection, the real advantages of robotic systems, the role of laparoscopy for Advanced Gastric Cancer, the reproducibility of a total intracorporeal technique and the oncological results achievable during long-term follow-up. A multi-institutional international database will be established to evaluate the role of robotic, laparoscopic and open approaches in gastric cancer, comprising of information regarding surgical, clinical and oncological features. A chart review will be conducted to enter data of participants with gastric cancer, previously treated at the participating institutions. The database is the first of its kind, through an international electronic submission system and a HIPPA protected real time data repository from high volume gastric cancer centres. This study is conducted in compliance with ethical principles originating from the Helsinki Declaration, within the guidelines of Good Clinical Practice and relevant laws/regulations. A multicentre study with a large number of patients will permit further investigation of the safety and efficacy as well as the long-term outcomes of robotic, laparoscopic and open approaches for the management of gastric cancer. NCT02325453; Pre-results.


Prevention of infection in the nursery.
Most infants are "sterile" when admitted to the newborn nursery. Rapid colonization of microorganisms in the infant then occurs. Colonization of virulent microorganisms can overwhelm the immature local and systemic immunity of a newborn infant. Cannulae, catheters, and assisted ventilation can bypass these fragile defenses. Effective infection control in the nursery attempts to reduce the exposure of the neonate to harmful microorganisms. Important measures include (1) the reduction of bacterial colonization through appropriate care of the umbilical stump and skin of the patient; (2) handwashing before and after contact with a patient; (3) low nurse-to-patient ratios; (4) cohorting of newborn infants; (5) isolation and cohorting of infected babies; (6) good hygiene among personnel; and (7) use of aseptic technique. Neonatal intensive care units have extraordinarily high infection rates. Most infants are on ventilators. Daily decontamination of respiratory equipment is essential. Regular monitoring of endotracheal cultures is useful, particularly when bacteria that are resistant to multiple antibiotics emerge.


Light-Controlled Histone Deacetylase (HDAC) Inhibitors: Towards Photopharmacological Chemotherapy.
Cancer treatment suffers from limitations that have a major impact on the patient's quality of life and survival. In the case of chemotherapy, the systemic distribution of cytotoxic drugs reduces their efficacy and causes severe side effects due to nonselective toxicity. Photopharmacology allows a novel approach to address these problems because it employs external, local activation of chemotherapeutic agents by using light. The development of photoswitchable histone deacetylase (HDAC) inhibitors as potential antitumor agents is reported herein. Analogues of the clinically used chemotherapeutic agents vorinostat, panobinostat, and belinostat were designed with a photoswitchable azobenzene moiety incorporated into their structure. The most promising compound exhibits high inhibitory potency in the thermodynamically less stable cis form and a significantly lower activity for the trans form, both in terms of HDAC activity and proliferation of HeLa cells. This approach offers a clear prospect towards local photoactivation of HDAC inhibition to avoid severe side effects in chemotherapy.


Nursing Implications for the Management of Lymphatic Malformation in Children [Formula: see text].
Lymphatic malformation (LM) is a benign congenital childhood growth that presents primarily at birth, with the remainder becoming evident by age 2 years. LM can cause devastating complications such as respiratory failure, dyspnea, dysphagia, organ compression, and nerve compression. Surgery is the preferred treatment option, although resection is not always an option due to the anatomic location of the malformation. Other treatments that have been tried with success include sclerotherapy, radiofrequency ablation, propranolol, and sirolimus. Nurses have an important role in caring for the child with LM, as with any complex disease. Nurses provide care at the bedside, education to the family, case coordination, and psychosocial support. LM is a rare disease in infancy necessitating pediatric nurses to support families through prolonged treatments and potential complications.


Is Smoking a Predictor for Acute Mountain Sickness? Findings From a Meta-Analysis.
Studies of the potential association between cigarette smoking and acute mountain sickness (AMS) have reached contradictory conclusions. Our aim was to perform a meta-analysis of studies across a range of populations to ascertain better the true relationship between cigarette smoking and AMS. We used the PRISMA protocol to identify and screen eligible studies of smoking and AMS. Databases including Pubmed and Google Scholar were searched, using the terms "smoking" and "acute mountain sickness." We conducted a meta-analysis of the selected studies in order to evaluate causal inference, evaluate potential biases, and investigate possible sources of heterogeneity across studies. We identified 3907 publications, of which 29 were eligible for inclusion by reporting smoking status and AMS. Of these, eight publications were excluded because they were duplicative or were lacking quantitative data. The 21 studies analyzed included 16 566 subjects. These fell into two groups: occupational/military (n = 8) or volunteers/trekkers/mixed (n = 13). Study heterogeneity was high (X (2) = 55.5, P < .001). Smoking was not statistically associated with increased risk of AMS: pooled OR = 0.88 (95% CI = 0.74-1.05). Stratification yielded similar risk estimates among the occupational/military studies versus all others and studies at relatively higher and lower altitudes. Overall, smoking was not statistically significantly associated with AMS: there is no consistent effect of cigarette smoking acting as either a protective factor against or a risk factor for AMS. This is the first quantitative assessment of published studies on smoking and AMS, which shows smoking to be neither a risk, nor protective. Studies specifically focusing on smoking as a risk factor, should guide further research on this issue. Although all smokers should be strongly advised to quit, studies on risk factors for AMS focusing on other exposures could shed light on the full range of risks for AMS.


Vibrational playback by means of airborne stimuli.
Substrate-borne vibrational communication is a common form of communication in animals. Current contact-based playback methods limit the number of substrates that can be stimulated simultaneously and potentially change the transmission properties of the substrate. Here, we explore a solution to these limitations by broadcasting airborne stimuli onto plant substrates to impart vibrational playbacks. We demonstrate that one can effectively compensate for the filtering properties of any individual plant across a range of frequencies. We then address how well both compensated broad-band and pure-tone stimuli for one plant individual apply to other individuals across days. Variation within and between plants was similar across the range tested but was quite variable at certain frequencies. Focusing on a subset of this range, at low frequencies, responses were flat across days and pure-tone frequency stimuli in this range were consistently transmitted despite repositioning of plants relative to the loudspeaker. Our results present a potential solution to researchers interested in exposing large samples of individuals to vibrational signals but also highlight the importance of validating the use of airborne stimuli as vibrational playbacks to the particular substrate type and frequency range of interest.


Ichthyosis hystrix.
The present report describes the condition in a three day old male child with bilateral ,linear, hyperpigmented and hyperkeratotic verrucous plaques and patchy alopecia over scalpe without any nail and skeletal abnormalities. It was suggestive of ichthyosis hystrix type of epidermal nevus,and is being reported in view of the rarity of this condition.


Test of a digestion optimization model: effects of costs of feeding on digestive parameters.
We tested predictions of a chemical reactor model of digestion by manipulating the short-term costs of feeding and then measuring the effect on digestive parameters. We compared residence time of digesta and extraction efficiency of glucose in cold-acclimated waxwings (Bombycilla cedrorum) feeding ad lib. and in birds whose costs of feeding were increased through the addition of intervals of time when they received no food. Such a feeding schedule simulated the ecological situation in which a frugivorous bird like a waxwing encounters food in patches and experiences nonfeeding periods as it searches for new preferred food patches. None of the results were consistent with the predictions of the optimal digestion model: extraction efficiency was independent of costs of feeding, and residence times did not increase as costs of feeding increased. This empirical evidence on the passage of digesta in waxwings suggests that movement of digesta in the guts of birds is much more complex than movement of material in an ideal chemical reactor. Tests of the optimal digestion model have involved manipulating food quality or the costs of feeding, and the conclusions are similar: compensatory modulation of retention time or digesta mixing and not rate of hydrolysis and absorption seem most important in maintaining the remarkably constant digestive efficiency.


Antioxidative activities and active compounds of extracts from Catalpa plant leaves.
In order to screen the Catalpa plant with high antioxidant activity and confirm the corresponding active fractions from Catalpa ovata G. Don, C. fargesii Bur., and C. bungei C. A. Mey., total flavonoid contents and antioxidant activities of the extracts/fractions of Catalpa plant leaves were determined. The determined total flavonoid content and antioxidant activity were used as assessment criteria. Those compounds with antioxidant activity were isolated with silica gel column chromatography and ODS column chromatography. Our results showed that the total flavonoid content in C. bungei C. A. Mey. (30.07 mg/g · DW) was the highest, followed by those in C. fargesii Bur. (25.55 mg/g · DW) and C. ovata G. Don (24.96 mg/g · DW). According to the determination results of total flavonoid content and antioxidant activity in 3 clones of leaves of C. bungei C. A. Mey., the total flavonoid content and antioxidant activity in crude extracts from C. bungei C. A. Mey. 6 (CA6) leaves were the highest. Moreover, the results showed that the total flavonoid content and antioxidant activities of ethyl acetate (EA) fraction in ethanol crude extracts in CA6 leaves were the highest, followed by n-butanol, petroleum ether (PE), and water fractions. Two flavonoid compounds with antioxidant activity were firstly isolated based on EA fraction. The two compounds were luteolin (1) and apigenin (2), respectively.