Functional elements and domains inferred from sequence comparisons of a heat shock gene in two nematodes.
Caenorhabditis elegans and Caenorhabditis briggsae are two closely related nematode species that are nearly identical morphologically. Interspecific cross-hybridizing DNA appears to be restricted primarily to coding regions. We compared portions of the hsp-3 homologs, two grp 78-like genes, from C. elegans and C. briggsae and detected regions of DNA identity in the coding region, the 5' flanking DNAs, and the introns. The hsp-3 homologs share approximately 98% and 93% identity at the amino acid and nucleotide levels, respectively. Using the nucleotide substitution rate at the silent third position of the codons, we have estimated a lower limit for the date of divergence between C. elegans and C. briggsae to be approximately 23-32 million years ago. The 5' flanking DNAs and one of the introns contain elements that are highly conserved between C. elegans and C. briggsae. Some of the regions of nucleotide identity in the 5' flanking DNAs correspond to previously detected identities including viral enhancer sequences, a heat shock element, and an element present in the regulatory regions of mammalian grp78 and grp94 genes. We propose that a comparison of C. elegans and C. briggsae sequences will be useful in the detection of potential regulatory and structural elements.


Crystal structure of interleukin-21 receptor (IL-21R) bound to IL-21 reveals that sugar chain interacting with WSXWS motif is integral part of IL-21R.
IL-21 is a class I cytokine that exerts pleiotropic effects on both innate and adaptive immune responses. It signals through a heterodimeric receptor complex consisting of the IL-21 receptor (IL-21R) and the common γ-chain. A hallmark of the class I cytokine receptors is the class I cytokine receptor signature motif (WSXWS). The exact role of this motif has not been determined yet; however, it has been implicated in diverse functions, including ligand binding, receptor internalization, proper folding, and export, as well as signal transduction. Furthermore, the WXXW motif is known to be a consensus sequence for C-mannosylation. Here, we present the crystal structure of IL-21 bound to IL-21R and reveal that the WSXWS motif of IL-21R is C-mannosylated at the first tryptophan. We furthermore demonstrate that a sugar chain bridges the two fibronectin domains that constitute the extracellular domain of IL-21R and anchors at the WSXWS motif through an extensive hydrogen bonding network, including mannosylation. The glycan thus transforms the V-shaped receptor into an A-frame. This finding offers a novel structural explanation of the role of the class I cytokine signature motif.


BML-111, a lipoxin receptor agonist, protects haemorrhagic shock-induced acute lung injury in rats.
The main pathogenesis of acute lung injury induced by haemorrhagic shock is inflammation. BML-111, a lipoxinA(4)-receptor agonist, promotes acute inflammatory resolution. We sought to elucidate whether BML-111 protects haemorrhagic shock-induced acute lung injury in rats. Thirty two adult male rats were randomized to sham group (sham), haemorrhagic shock/resuscitation (HS), HS plus BML-111 (BML-111), and HS plus BML-111 and BOC-2 (BOC-2). Haemorrhagic shock was induced by blood drawing, and then resuscitation was obtained by infusion of shed blood and two-fold volume saline. Histological findings, as well as assays of neutrophilic infiltration (myeloperoxidase activity, ICAM-1 expression), inflammatory cytokines and pro-inflammatory factor (IκB-α and NF-κB p65) confirmed that haemorrhagic shock induced acute lung injury. BML-111 significantly mitigated acute lung injury induced by haemorrhagic shock. However, BOC-2, an antagonist of the lipoxinA(4)-receptor, partially reversed the protective effect of BML-111 on the haemorrhagic shock-induced the acute lung injury. BML-111 protects haemorrhagic shock-induced acute lung injury in rats.


The role of C1q in recognition of apoptotic epithelial cells and inflammatory cytokine production by phagocytes during Helicobacter pylori infection.
Gastric epithelial cells (GECs) undergo apoptosis during H. pylori infection and phagocytes within the mucosa engulf these cells. The recognition and clearance of apoptotic cells is a multifactorial process, enhanced by the presence of various bridging molecules and opsonins which are abundant in serum. However, it is not clear how recognition or clearance may differ in the context of H. pylori infection induced apoptosis. In addition, efferocytosis of sterile apoptotic cells is known to confer anti-inflammatory properties in the engulfing phagocyte, however it is unknown if this is maintained when phagocytes encounter H. pylori-infected cells. Thus, the ability of macrophages to bind and engulf gastric epithelial cells rendered apoptotic by H. pylori infection and the association of these interactions to the modulation of phagocyte inflammatory responses was investigated in the absence and presence of serum with a particular focus on the role of serum protein C1q. Control (uninfected) or H. pylori-infected AGS cells were co-cultured with THP-1 macrophages in the presence or absence of serum or serum free conditions + C1q protein (40-80 μg/mL). Binding of AGS cells to THP-1 macrophages was assessed by microscopy and cytokine (IL-6 and TNF-α) release from LPS stimulated THP-1 macrophages was quantified by ELISA. We show that macrophages bound preferentially to cells undergoing apoptosis subsequent to infection with H. pylori. Binding of apoptotic AGS to THP-1 macrophages was significantly inhibited when studied in the absence of serum and reconstitution of serum-free medium with purified human C1q restored binding of macrophages to apoptotic cells. Co-culture of sterile apoptotic and H. pylori-infected AGS cells both attenuated LPS-stimulated cytokine production by THP-1 macrophages. Further, direct treatment of THP-1 macrophages with C1q attenuated LPS stimulated TNF-α production. These studies suggest that C1q opsonizes GECs rendered apoptotic by H. pylori. No differences existed in the ability of infected or sterile apoptotic cells to attenuate macrophage cytokine production, however, there may be a direct role for C1q in modulating macrophage inflammatory cytokine production to infectious stimuli.


MUC6 apomucin shows a distinct normal tissue distribution that correlates with Lewis antigen expression in the human stomach.
Among the human mucin complementary DNAs thus far identified, two (MUC5AC and MUC6) were cloned from stomach libraries. This study examines the distribution of MUC6 in normal tissues and compares it with that of MUC5AC as well as with the expression of Lewis blood group antigens. Affinity-purified rabbit antibodies detecting epitopes within the repetitive sequence of MUC5AC and MUC6 were used in enzyme-linked immunosorbent assays and immunohistochemical assays. RNA expression was analyzed by in situ hybridization. Double-labeling immunofluorescence was used to study apomucin and Lewis antigen coexpression. MUC6 is detected in the stomach, colon, gallbladder, and endocervix. Two patterns of staining are observed, perinuclear and diffuse cytoplasmic, possibly reflecting differences in MUC6 glycosylation. Using both immunohistochemical assays and in situ hybridization on stomach tissue sections, MUC6 is expressed mainly in antral mucous cells, whereas MUC5AC is detected mainly in the superficial epithelium and neck glands. In antral mucosa, MUC6+ cells express Lewis(y), whereas MUC5AC+ cells express Lewis(b) and sialyl-Lewis(a). It was concluded that MUC6 has a distinct tissue distribution pattern, different from that of MUC1-MUC5; MUC5AC and MUC6 are expressed by different cellular populations in normal stomach; and in this tissue, MUC5AC+ cells and MUC6+ cells show different patterns of Lewis antigen expression.


Reliability of 3-dimensional surface imaging of the face using a whole-body surface scanner.
To the knowledge of the authors, no data about the reproducibility and accuracy of 3-dimensional surface imaging of the face using a whole-body scanner are available. Thus, the objective of this investigation was to assess the reproducibility of facial scans acquired using a whole-body imaging device. This investigation investigated 220 3-D scans of a total of 22 healthy volunteers (with a mean age of 29.36 years). Two consecutive 3-D images using a Vectra WB360 of the volunteers were obtained utilizing a whole-body imaging device. Predefined distances in the face were performed in each scan and compared. Furthermore, surface deviation between two consecutively captured scans was assessed. The distance with the smallest statistical significance was found to be at the nose with p = 0.998, while the biggest statistical significance was found in the midface with p = 0.658. The area with the biggest surface deviation between the superimposed scans was the neck with a root mean square (RMS) of 1.62 ± 1.71, and the area with the smallest surface deviation was the forehead with a RMS of 0.17 ± 0.05. The whole-body imaging device investigated in this study can be utilized to capture the face and provides enough accuracy to compare scans. Even though not directly investigated, it can be hypothesized that the error caused by repositioning the patient between a baseline and a follow-up scan will not be too big to consider measurements performed with the whole-body imaging device as impractical.


Long non-coding RNA LINC00504 regulates the Warburg effect in ovarian cancer through inhibition of miR-1244.
Ovarian cancer (OC) is the most lethal gynecologic malignancy and long non-coding RNAs (lncRNAs) have been acknowledged as important regulators in human OC. This study aimed to investigate the function and underlying mechanisms of LINC00504 in OC. The expression levels of LINC00504 in human OC tissues and cell lines were investigated by qRT-PCR analysis. The OC cell proliferation, and apoptosis were evaluated by MTT assay, colony-formation assay, Caspase-3 activity assay, and nucleosome ELISA assay, respectively. The metabolic shift in OC cells was examined by aerobic glycolysis analysis. Dual-luciferase activity reporter assay and mRNA-miRNA pull-down assay were conducted to validate the interaction between LINC00504 and miR-1244. LINC00504 was upregulated in OC cell lines and specimens. Knockdown of LINC00504 inhibited cell proliferation, enhanced apoptosis, decreased glycolysis-related gene (PKM2, HK2, and PDK1) expression, and altered aerobic glycolysis in OC cells and vice versa. LINC00504 downregulated miR-1244 expression levels by acting as an endogenous sponge of miR-1244. Inhibition of miR-1244 diminished the effects of LINC00504 on OC cells. Our study shows that LINC00504 promotes OC cell progression and stimulates aerobic glycolysis by interacting with miR-1244, which indicates that LINC00504 might act as a promising therapeutic target for OC treatment.


Prevention of vitamin D deficiency in children following cardiac surgery: study protocol for a randomized controlled trial.
Vitamin D is a pleiotropic hormone important for the recovery of organ systems after critical illness. Recent observational studies have suggested that three out of every four children are vitamin D deficient following cardiac surgery, with inadequate preoperative intake and surgical losses playing important contributory roles. Observed associations between postoperative levels, cardiovascular dysfunction and clinical course suggest that perioperative optimization of vitamin D status could improve outcome. With this two-arm, parallel, double blind, randomized controlled trial (RCT), we aim to compare immediate postoperative vitamin D status in children requiring cardiopulmonary bypass for congenital heart disease who receive preoperative daily high dose vitamin D supplementation (high-dose arm) with those who receive usual intake (low-dose arm). Eligibility requirements include age (>36 weeks, <18 years) and a congenital heart defect requiring cardiopulmonary bypass surgical correction. Enrollment of 62 participants will take place at a single Canadian tertiary care center over a period of 2 years. Children randomized to the high-dose group will receive age-based dosing that was informed by the Institute of Medicine (IOM) daily tolerable upper intake level (<1 year old = 1,600 IU/day, >1 year old = 2,400 IU/day). Children in the low-dose arm will receive usual care based on IOM recommendations (<1 year old = 400 IU, >1 year old = 600 IU). The primary outcome measure is immediate postoperative vitamin D status, using blood 25(OH)D. Maintaining adequate postoperative vitamin D levels following surgery could represent an effective therapy to speed recovery following CHD surgery. The proposed research project will determine whether preoperative supplementation with a dosing regimen based on the IOM recommended daily upper tolerable intake will prevent postoperative vitamin-D deficiency in the majority of children. The results will then be used to inform the design of a large international RCT exploring whether preoperative optimization of vitamin D status might improve short and long-term outcomes in this vulnerable population. Clinicaltrials.gov Identifier--NCT01838447 Date of registration: 11 April 2013.


Discovery of benzhydrol-oxaborole derivatives as Streptococcus pneumoniae leucyl-tRNA synthetase inhibitors.
Pneumonia caused by bacterium S. pneumoniae is a severe acute respiratory infectious disease with high morbidity and mortality, especially for children and immunity-compromised patients. The emergence of multidrug-resistant S. pneumoniae also presents a challenge to human health. Leucyl-tRNA synthetase (LeuRS) catalyzes the attachment of l-leucine to tRNALeu, which plays an essential role in protein translation and is considered an attractive antimicrobial drug target. In the present work, benzhydrol-oxaborole hybrid compounds were designed and synthesized as inhibitors of S. pneumoniae LeuRS. Exploration of the phenyl ring near Lysine 389 eventually yielded compounds 46 and 54 with submicromolar inhibitory potency. The co-crystal of compound 54 in the editing domain pocket of SpLeuRS was obtained and confirmed the formation of an additional hydrogen bond between the carbonyl of 54 and Lysine 389. It also showed anti-pneumococcal activity in vitro. The structure-activity relationship was discussed. This work will provide an essential foundation for the further development of anti-pneumococcal agents by targeting LeuRS.


Effects of DTL electrode position on the amplitude and implicit time of the electroretinogram.
This study sought to investigate whether there is an optimal position of the Dawson, Trick, and Litzkow (DTL) electrodes when measuring the full-field electroretinogram (ERG) for monitoring purposes. In 200 uveitis patients, an extended light-adapted (LA) ERG protocol was measured twice, incorporating the International Society for Clinical Electrophysiology of Vision standards. First, a LA ERG was measured with the DTL in the lower lid position (LLP) and thereafter in the fornix position. Differences in amplitudes and implicit times of a-waves, b-waves, and the 30 Hz peak were investigated. Intraclass correlation coefficients (ICCs) as well as coefficients of variation (CoV) were calculated, to assess both reliability and relative variability between the two DTL positions. Implicit times showed no statistically significant differences between the two DTL positions. As expected, amplitudes at the different stimulus strengths were 1.12-1.19 higher in the LLP, but there were no significant differences in the CoV between the two DTL positions. The ICC was high for the b-wave and 30 Hz flicker response (0.842-0.979), but lower for the a-wave, especially for amplitudes (0.584-0.716). For monitoring purposes in patients, we conclude that based on relative variability, no position is preferable above the other. However, because in most diseases amplitudes are decreased, the LLP may be chosen because it yields higher amplitudes. Whatever the choice, it is important to ensure that the DTL position remains stable during an ERG recording.


Organ movements and dose exposures in teletherapy of prostate cancer using a rectal balloon.
During radiotherapy of localized prostate cancer, organ movements for the dose exposure of organs at risk like rectum, urinary bladder and urethra play, inter alia, a significant role. One possibility of internal organ stabilizing is offered by the usage of a rectal balloon during radiotherapy. The influence on organ movements and dose allocation of the organs at risk is unknown. Twelve patients (Table 1) were characterized based on planning-CT's regarding organ movements and organ doses using a rectal balloon, inflated with 0 ml and 60 ml air. For the determination of the organ doses, three-dimensional conformal radiation plans (3-field-pelvis box) with a cumulative dose of 59.4 Gy were created, and the dose-volume-histograms for the anterior rectal wall, the posterior rectal wall, the rectal mucosa, the whole rectum, as well as the urinary bladder were compared (Figures 1 and 2). The application of a 60 ml air-filled rectal balloon during each fraction of teletherapy led to significant organ movements of the anterior and posterior rectal wall and to a reduction of the transversal prostate diameter, as well as to a changed organ dose exposure of the organs at risk. A ventral shift of the anterior rectal wall (maximum 0.8 cm, mean 0.4 cm) was shown, as well as a dorsal shift of the posterior rectal wall (maximum 1.2 cm, mean 0.7 cm), associated with a transversal prostate diameter decrease (maximum 0.8 cm, mean 0.3 cm) (Table 2, Figure 3). The organ dose of the anterior rectal wall increased significantly (maximum 1.3 Gy, mean 0.5 Gy) during application of a rectal balloon, the one of the posterior rectal wall decreased significantly (maximum 18.6 Gy, mean 6.5 Gy). Related to the entire rectal mucosa and the rectum as a complete organ, a decrease of the maximum doses was shown (rectal mucosa: maximum 9.1 Gy, mean 3.0 Gy; rectum: maximum 9.4 Gy, mean 3.7 Gy). The organ dose of the urinary bladder did not show significant changes (Tables 3 and 4, Figures 4 to 7). The application of a rectal balloon in teletherapy of localized prostate cancer leads to significantly changed dose exposition of organs at risk. The decreased dose exposure of the posterior rectal wall and the rectal mucosa is opposed by the higher organ dose of the anterior rectal wall. It has to be shown weather documented organ dose exposure is associated with short and long-term consequences.


Oral ulceration as a presenting sign of unknown sarcoidosis mimicking a tumour: report of 2 cases.
Oral lesions seem to be rather infrequent in sarcoidosis, and only 43 cases have been described in the English literature. Clinically most oral lesions appear as non-tender well-circumscribed swellings or submucosal nodules. Superficial ulceration is unusual. The authors present two cases in which the first presenting symptom of an unknown sarcoidosis was the presence of an oral ulcerated lesion with indurated margins that could easily have been misdiagnosed for a squamous cell carcinoma. It must be stressed that in all ulcerated lesions of the oral cavity, squamous cell carcinoma must always be considered in the differential diagnosis.


Malignant histiocytosis of the intestine. Its relationship to malabsorption and ulcerative jejunitis.
The clinical and histopathologic features in seven patients with intestinal lymphoma are reported. Three of these presented with ulcerative jejunitis and four with overt lymphomas. A short history of abdominal pain with weight loss followed by intestinal obstruction, hemorrhage, or perforation characterized all the patients except one in whom a nine year history of malabsorption preceded the acute phase of the disease. Malabsorption was demonstrated in four of the patients, and all showed villous atrophy with crypt hyperplasia of the jejunum remote from areas of ulceration or frank lymphoma. The malignant lymphoma cells showed varying degrees of pleomorphism and exhibited phagocytosis of platelets, red cells, and cell debris. The accompanying infiltrate of inflammatory cells often overshadowed the neoplastic histiocytes, and in those cases showing little pleomorphism these cells could be easily overlooked. In the intestine the tumor cells were usually present as a diffuse infiltrate in the lamina propria or within the bases of ulcers and in five of seven cases did not give rise to macroscopic tumor masses. In all patients dissemination of tumor cells to the lymph nodes, liver, spleen, and bone marrow was evident, the infiltrate in all these organs resembling that seen in malignant histiocytosis. The morphology of the tumor cells, their phagocytic nature, the diffuse character of the tumor infiltrate, and the pattern of dissemination suggest that this lesion should be designated malignant histiocytosis of the intestine rather than histiocytic lymphoma (reticulum cell sarcoma). It is suggested that the tumor may arise from cells of monocyte-histiocyte lineage normally present in the lamina propria of the gut and that a prolonged cryptic phase accompanied, and often overshadowed, by an inflammatory reaction may give rise to malabsorption and ulcerative jejunitis before overt lymphoma is manifest.


Use of low frequency and density ultrasound to stimulate partial nitrification and simultaneous nitrification and denitrification.
Low frequency and density ultrasound has attracted considerable attention in enhancing wastewater treatment performance, particularly in the removal of nitrogen. In the present study, two sequencing batch reactors were operated to confirm the effects of ultrasound at the frequency of 40 kHz and density of 0.027 W/mL on partial nitrification and simultaneous nitrification and denitrification (SND). At the optimal irradiation time of 2.0 h, the obtained nitrite accumulation ratio and SND efficiency at full aerobic were 73.9% and 72.8%, respectively. Nitrite accumulation was the result of increased NH4(+)-N removal and improved ammonia oxidizing bacteria (AOB) activity with simultaneous inhibition of nitrite oxidizing bacteria (NOB) activity. Ultrasonic treatment could provide suitable conditions in temperature and pH for AOB growth, and destroy the NOB community structure. Moreover, organic matters were released and offered an additional carbon source for denitrification apart from the negative effects on sludge properties.


Auxin transport.
Polar transport of auxin is essential for normal plant growth and development. On a cellular level, directional auxin transport is primarily controlled by an efflux carrier complex that is characterized by the PIN-FORMED (PIN) family of proteins. Detailed developmental studies of PIN distribution and subcellular localization have been combined with the analysis of changes in localized auxin levels to map PIN-mediated auxin movement throughout Arabidopsis tissues. Plant orthologs of mammalian multidrug-resistance/P-glycoproteins (MDR/PGPs) also function in auxin efflux. MDR/PGPs appear to stabilize efflux complexes on the plasma membrane and to function as ATP-dependent auxin transporters, with the specificity and directionality of transport being provided by interacting PIN proteins.


The ER calcium channel Csg2 integrates sphingolipid metabolism with autophagy.
Sphingolipids are ubiquitous components of membranes and function as bioactive lipid signaling molecules. Here, through genetic screening and lipidomics analyses, we find that the endoplasmic reticulum (ER) calcium channel Csg2 integrates sphingolipid metabolism with autophagy by regulating ER calcium homeostasis in the yeast Saccharomyces cerevisiae. Csg2 functions as a calcium release channel and maintains calcium homeostasis in the ER, which enables normal functioning of the essential sphingolipid synthase Aur1. Under starvation conditions, deletion of Csg2 causes increases in calcium levels in the ER and then disturbs Aur1 stability, leading to accumulation of the bioactive sphingolipid phytosphingosine, which specifically and completely blocks autophagy and induces loss of starvation resistance in cells. Our findings indicate that calcium homeostasis in the ER mediated by the channel Csg2 translates sphingolipid metabolism into autophagy regulation, further supporting the role of the ER as a signaling hub for calcium homeostasis, sphingolipid metabolism and autophagy.


Mitochondrial oxidative alterations following partial hepatectomy.
Mitochondria, isolated from rat livers during the early phase of liver regeneration (7-24 h after partial hepatectomy), show: (i) decrease in the rate of ATP synthesis; (ii) increase of malondialdehyde and of oxidized protein production; (iii) decrease of the content of intramitochondrial glutathione and of protein thiols on mitochondrial proteins; (iv) increase of the glutathione bound to mitochondrial proteins by disulfide bonds. These observations suggest an increase of production of oxygen radicals in liver mitochondria, following partial hepatectomy, which can alter the function of the enzymes involved in the oxidative phosphorylation. Blue-native gel electrophoresis of rat liver mitochondria, isolated after partial hepatectomy, shows, during the early phase of liver regeneration (0-24 h after partial hepatectomy), a progressive decrease of the content of F0F1-ATP synthase complex. The amount of glutathione bound to the F0F1-ATP synthase, electroeluted from the blue-native gels, progressively increased during the early phase of liver regeneration. It is concluded that partial hepatectomy causes mitochondrial oxidative stress that, in turn, modifies proteins (such as F0F1-ATP synthase) involved in the mitochondrial oxidative phosphorylation.


Comparison of the indirect enzyme-linked immunosorbent assay (ELISA) with the complement fixation test (CFT) for the serodiagnosis of bovine brucellosis.
Complement fixation and ELISA tests were carried out on 8772 bovine sera. Results showed that ELISA titres were, on average, approximately sixteen times higher than the corresponding C.F. titres. The specificity of ELISA appeared comparable to that of the C.F.T. There was no evidence to show that the ELISA could detect infection earlier than the C.F.T.


[Chemotherapeutic failure in micrometastasis in peripheral blood of patients with colorectal carcinomas].
To study chemotherapeutic failure in the micrometastasis in peripheral blood of patients with colorectal carcinomas and its clinical significance. We investigated the changes of micrometastasis in peripheral blood of patients with colorectal carcinomas before and after chemotherapy. The positive rate of CK2O mRNA in peripheral blood was 58.3%. Five more positive cases were detected 3 days after operation than before operation. After early short-term chemotherapy following operation, 22 cases turned to be negative. The maintaince of micrometastasis in peripheral blood after chemotherapy was significantly related to bcl-2 expression and p53 mutation in cancer tissues. The early short-term chemotherapy after operation plays a role in controlling the micrometastasis of colorectal carcinoma. The study of chemotherapeutic effect on micrometastasis in peripheral blood and its relation with the related genes may contribute to the selection of drugs and plans of adjuvant treatment.


Global profiling of the proteomic changes associated with the post-testicular maturation of mouse spermatozoa.
Spermatozoa acquire fertilization potential during passage through a highly specialized region of the extratesticular ductal system known as the epididymis. In the absence of de novo gene transcription or protein translation, this functional transformation is extrinsically driven via the exchange of varied macromolecular cargo between spermatozoa and the surrounding luminal plasma. Key among these changes is a substantive remodeling of the sperm proteomic architecture, the scale of which has yet to be fully resolved. Here, we have exploited quantitative mass spectrometry-based proteomics to define the extent of changes associated with the maturation of mouse spermatozoa; reporting the identity of >6,000 proteins, encompassing the selective loss and gain of several hundred proteins. Further, we demonstrate epididymal-driven activation of RHOA-mediated signaling pathways is an important component of sperm maturation. These data contribute molecular insights into the complexity of proteomic changes associated with epididymal sperm maturation.


Longitudinal Changes of Subpubic Arch Angle throughout Pregnancy.
The objective of this study is to assess whether the subpubic arch angle (SPA) changes throughout pregnancy. We recruited a group of nulliparous women in the first trimester of pregnancy. Each woman was assessed 3 times throughout pregnancy, once per each trimester, by measuring SPA using a recently described highly reproducible three-dimensional transperineal ultrasound (linear reconstruction with contrast enhancement technique; OmniView-volume contrast imaging). Repeated measures analysis of variance was used to study SPA changes during pregnancy. Overall, 97 women were included in the final analysis. SPA increased progressively and significantly (F = 27.824, p < 0.001) from the first to the second trimester (121.8 ± 8.7 vs. 123.5 ± 8.4°, p = 0.01) and from the second to the third trimester (123.5 ± 8.4 vs. 125.3 ± 8.1°, p = 0.01). SPA width increases progressively but slightly during pregnancy. Although this finding is interesting, the extremely small difference detected is unlikely to be clinically significant.


Temperature and water regulation of gas exchange of Opuntia polyacantha.
Opuntia polyacantha was collected from the shortgrass prairie in Colorado. Carbon dioxide and water vapor exchange was monitored in plants pretreated and analyzed under cool temperatures (20/15°C) and warm temperatures (35/15°C). Well watered plants under a 35/15 thermoperiod supported the fixation of atmospheric CO2 during the night, early morning, and late afternoon. Plants under a 20/15 thermoperiod exhibited CO2 uptake only during the afternoon. The fixation of CO2 at night could be stimulated or induced by decreasing the night temperature. Plants from which water was withheld two or four weeks showed a decline in CO2 fixation with the uptake at night exhibiting the greatest sensitivity. Under conditions of water stress the enhancement of CO2 uptake at night by cool night temperatures was largely lost. Plants water stressed for 4 weeks recovered rapidly upon rewatering under warm or cool temperatures. Rates of CO2 fixation were comparable to well watered plants within 24 h. The effects of temperature and water stress on gas exchange are compared to the in situ growth pattern of O. polyacantha and contrasted with the regulation of gas exchange observed in C3 and C4 grasses of the shortgrass prairie.


Risk factors in amblyopia.
Any intervention to prevent serious amblyopia is based on the knowledge about normal versus subnormal visual development. Our ability to predict with high degree of certainty which children will develop amblyopia will be dependent on the characteristics of various risk factors for initiating the development of squint or amblyopia. We have used longitudinal studies of population based cohorts of young children to define some of these risk factors such as refractive errors. Three hundred and ten children with an astigmatism greater than or equal to 1.0 D at one year of age were refracted yearly between the age one and four years. Astigmatism and anisometropia were found to be highly variable during infancy and early childhood. Longitudinal follow-up seems to be needed to separate the normal from the abnormal refraction development, which initiates the development of the amblyopia. Children with constant or increasing astigmatism or anisometropia between one and four years were 'at risk'. In parallel we have studied important factors for successful treatment of amblyopia. Based on these findings we conclude that a population screening at four years of age seems to be advantageous in Sweden in order detect and successfully treat most cases of amblyopia.


Regulatory B cells in autoimmunity: developments and controversies.
Over a decade has now passed since the concept of B cells with a regulatory function was resurrected--B cells that produce antibodies with a suppressive effect were first reported in the 1960s and suppressor B cells in the 2000s. In the meantime, some aspects of regulatory B (B(REG))-cell biology have been elucidated. Not only have scientists begun to unravel the mechanism of how B(REG) cells suppress immune responses and which cells they target, but their ontogeny and development has also begun to be determined. To date, key roles for B(REG) cells have been identified in the regulation of several immune-mediated processes, including autoimmunity and responses to infectious disease and cancer. This Review highlights these advances in the study of B(REG) cells, and outlines what is known about their phenotype as well as their suppressive role in autoimmunity from studies in both mice and humans. A particular emphasis is placed on B(REG)-cell function in rheumatic diseases.


Contributions of specific causes of death by age to the shorter life expectancy in depression: a register-based observational study from Denmark, Finland, Sweden and Italy.
The reasons for the shorter life expectancy of people with depression may vary by age. We quantified the contributions of specific causes of death by age to the life-expectancy gap in four European countries. Using register-based cohort data, we calculated annual mortality rates in between 1993 and 2007 for psychiatric inpatients with depression identified from hospital-care registers in Denmark, Finland and Sweden, and between 2000 and 2007 for antidepressant-treated outpatients identified from medication registers in Finland and Turin, Italy. We decomposed the life-expectancy gap at age 15 years by age and cause of death. The life-expectancy gap was especially large for psychiatric inpatients (12.1 to 21.0 years) but substantial also for antidepressant-treated outpatients (6.3 to 14.2 years). Among psychiatric inpatients, the gap was largely attributable to unnatural deaths below age 55 years. The overall contribution was largest for suicide in Sweden (43 to 45%) and Finland (37 to 40%). In Denmark, 'other diseases' (25 to 34%) and alcohol-attributable causes (10 to 18%) had especially large contributions. Among antidepressant-treated outpatients, largest contributions were observed for suicide (18% for men) and circulatory deaths (23% for women) in Finland, and cancer deaths in Turin (29 to 36%). Natural deaths were concentrated at ages above 65 years. The indication of antidepressant prescription could not be ascertained from the medication registers. Interventions should be directed to self-harm and substance use problems among younger psychiatric inpatients and antidepressant-treated young men. Rigorous monitoring and treatment of comorbid somatic conditions and disease risk factors may increase life expectancy for antidepressant-treated outpatients, especially women.


Alcohol, nitric oxide, and neurotoxicity: is there a connection?--a review.
A hypothesis is presented to explain the influence of alcohol on glutamate generated excitotoxicity. Chronic alcohol exposure is reported to increase glutamate-N-methyl-D-aspartate (NMDA) receptors and calcium ion channel activity, resulting in the neurotoxicity and seizure activity associated with alcohol withdrawal in certain persons. Recent information indicates that nitric oxide is responsible for the neurotoxicity associated with excessive glutamate stimulation of NMDA receptors. Thus, it is hypothesized that nitric oxide is involved in producing the neurotoxicity and cell disturbances associated with chronic alcohol exposure.


Inhibition of Dunning tumor growth by melatonin.
Injections of the pineal hormone melatonin reduced growth and increased doubling time of the R3327H Dunning prostatic adenocarcinoma in the Copenhagen X Fisher rat. This occurred even though testosterone levels (50% of normal) were ostensibly high enough to maintain normal tumor growth. Melatonin may act directly upon the conversion of testosterone to dihydrotestosterone to inhibit tumor growth. Alternatively, a more complicated mechanism may be involved since studies on MCF breast cancer tissue indicate an estrogen requirement for inhibition of growth by melatonin.


Sonolytic degradation of dimethoate: kinetics, mechanisms and toxic intermediates controlling.
The sonolytic degradation of aqueous solutions of dimethoate, O,O-dimethyl S-[2-(methylamino)-2-oxoethyl]dithiophosphate, was examined. Optimal degradation rates were obtained at 619 kHz for continuous sonolysis and 406 kHz for pulse sonolysis. The primary pathways for degradation include hydroxyl radical oxidation, hydrolysis and pyrolysis on collapsing cavitation bubble interfaces. Reaction mechanisms coupled with the corresponding kinetic models are proposed to reproduce the observed concentration versus time profiles for dimethoate, omethoate and N-(methyl) mercaptoacetamide during sonolysis. The oxidation and hydrolysis of dimethoate and omethoate occurred at the water-bubble interface was the rate-determining step for sonolytic overall degradation of dimethoate. More than 90% toxicity of dimethoate was reduced within 45 min ultrasonic irradiation. Ferrous ion at micro molar level can significantly enhance the sonolytic degradation of dimethoate and effectively reduce the yields of toxic intermediate omethoate.


Paracoccidioides brasiliensis induces recruitment of α3 and α5 integrins into epithelial cell membrane rafts, leading to cytokine secretion.
Paracoccidioides brasiliensis is one of the etiological agents of paracoccidioidomycosis, a human systemic mycosis, highly prevalent in Latin America. In the present work, we demonstrate that P. brasiliensis yeasts promote IL-6 and IL-8 secretion by the human lung epithelial cell line A549 in an integrin-dependent manner. In fact, small interfering RNA directed to α3 and α5 integrins decreased IL-6 and IL-8 levels in P. brasiliensis-infected A549 cell cultures. This fungus also led to an increase in the expression of α3 and α5 integrins in this epithelial cell line. In addition, P. brasiliensis yeasts promoted α3 and α5 integrins clustering into A549 cell membrane rafts. Furthermore, epithelial cell membrane raft disruption with nystatin decreased IL-6 and IL-8 levels in P. brasiliensis-A549 cell cultures. Therefore, by increasing host α3 and α5 integrins levels and clustering these receptors into membrane rafts, P. brasiliensis yeasts may modulate host inflammation.


An experimental study of a splenic inhibitory factor influencing hepatic regeneration.
The effect of splenectomy on hepatic regeneration after 70 per cent partial hepatectomy was studied in rats. Compared with nonsplenectomized rats, preliminarily splenectomized rats showed significantly increased weights of the liver in the early stage (up to four days) after hepatectomy and significantly promoted deoxyribonucleic acid synthesis in the regenerating liver in terms of high levels of 3H-thymidine uptake, thymidine kinase activity and mitotic index in the residual liver 24 hours after hepatectomy. The splenic factor inhibiting hepatic regeneration, as previously suggested, was investigated by using primary cultures of rat hepatocytes. At 48 hours when the 3H-thymidine uptake by cultured hepatocytes reached maximum, the group containing a splenic extract showed significantly lower levels (p less than 0.005) of uptake than did the group without the extract and the group containing splenic venous serum also showed lower levels. This splenic factor was labile against heat and lost activity by trypsinization. Furthermore, gel filtration by the use of Sephadex G-75 column suggested the factor to be a protein-like substance with a molecular weight of 50,000 to 60,000. It is likely that a protein-like substance inhibiting hepatic regeneration after hepatectomy is present in the spleen.


Response suppression, strategy application, and working memory in the prediction of academic performance and classroom misbehavior: A neuropsychological approach.
Neurological illness can produce a disorganization of behavior, including verbal disinhibition, despite apparent preserved intelligence. Neuropsychological tests of such behavioral control mechanisms may predict real-world performance of healthy people, such as success or misbehavior in educational contexts. In two separate studies, we examined how the Hayling Test of verbal response suppression predicts grades and classroom misbehavior. Verbal suppression errors and spontaneous strategy use were significant predictors of undergraduate grades. Using a modified version of the Hayling Test designed to reduce strategic responding with high school students (mean age 16), higher grades were predicted by shorter response suppression latencies and better working memory scores, and classroom misbehavior was predicted by lower working memory scores. Verbal response suppression and spontaneous strategy use, both closely linked to disorganized behavior in neuropsychological patients, predict academic achievement but seem unrelated to classroom misbehavior, which is associated with weakness in working memory.


Inflammatory markers predict episodes of wheezing during the first year of life in Bangladesh.
Environmental factors that influence wheezing in early childhood in the developing world are not well understood and may be useful in predicting respiratory outcomes. Therefore, our objective was to determine the factors that can predict wheezing. Children from Dhaka, Bangladesh were recruited at birth and episodes of wheezing were measured alongside nutritional, immunological and socioeconomic factors over a one-year period. Poisson Regression with variable selection was utilized to determine what factors were associated with wheezing. Elevated serum IL-10 (rate ratio (RR) = 1.51, 95% confidence interval (CI): 1.22-1.87), IL-1β (RR = 1.55, 95% CI: 1.26-1.93) C-reactive protein (CRP) (RR = 1.41, 95% CI: 1.03-1.93) in early life, and male gender (RR = 1.52, 95% CI: 1.27-1.82) predicted increased wheezing episodes. Conversely, increased fecal alpha-1-antitrypsin (RR = 0.87, 95% CI: 0.76-1.00) and family income (RR = 0.98, 95% CI: 0.97-0.99) were associated with a decreased number of episodes of wheezing. Systemic inflammation early in life, poverty, and male sex placed infants at risk of more episodes of wheezing during their first year of life. These results support the hypothesis that there is a link between inflammation in infancy and the development of respiratory illness later in life and provide specific biomarkers that can predict wheezing in a low-income country.


Strategies for success in online learning.
The nursing and nursing faculty shortages have created a greater need for effective online learning strategies. Today's learners require the flexibility offered by online learning, but only when well grounded in sound teaching-learning principles. This article describes strategies for online learning designed to keep the needs of today's learners in mind. These strategies are focused on the resolution of technology problems as well as the learning process.


No oceans on Titan from the absence of a near-infrared specular reflection.
With its substantial atmosphere of nitrogen, hydrocarbons and nitriles, Saturn's moon Titan is a unique planetary satellite. Photochemical processing of the gaseous constituents produces an extended haze that obscures the surface. Soon after the Voyager fly-bys in 1980 and 1981 photochemical models led to the conclusion that there should be enough liquid methane/ethane/nitrogen to cover the surface to a depth of several hundred metres. Recent Earth-based radar echoes imply that surface liquid may be present at a significant fraction of the locations sampled. Here we present ground-based observations (at near-infrared wavelengths) and calculations showing that there is no evidence thus far for surface liquid. Combined with the specular signatures from radar observations, we infer mechanisms that produce very flat solid surfaces, involving a substance that was liquid in the past but is not in liquid form at the locations we studied.


Effect of drugs, peptide hormones and lipogenic precursors on the relative incorporation of [3H]H2O and carbon into hepatic cholesterol.
Measurement of the weight of desmosterol produced during its biosynthesis in the presence of tritiated water and triparanol has permitted a direct determination of the relative flux of carbon and tritium (the H/C ratio) into sterol in hepatocytes. The H/C ratio increased with time of incubation irrespective of the nutritional state of the donor animals. This increase was more marked in hepatocytes from starved animals. Pyruvate and lactate increased, and glucagon decreased, the sterol H/C ratio. Addition of pyruvate to incubations containing glucagon resulted in a 32-67% increase in the H/C ratio depending upon nutritional status. Insulin had no effect whilst (-)-hydroxycitrate decreased the ratio by 25%.


Evidence for Noncytosine Epigenetic DNA Modifications in Multicellular Eukaryotes: An Overview.
Cytosine DNA methylation (5-methylcytsone, 5mC) is the major DNA modification found in the genomes of animals and plants. Although the roles of 5mC and its oxidized derivatives in the regulation of gene expression are relatively well attested and extensively explored, a number of recent studies imply that noncytosine DNA modifications may also convey specific biological functions and act as "epigenetic" marks in multicellular organisms. Here we review experimental evidence for the presence of noncytosine epigenetic modifications in metazoans and plants focusing on two "unusual" DNA bases, 5-hydroxymethyluracil (5hmU) and N6-methyladenine (6mA), and suggest potential explanations for inconsistencies in the currently available data on abundance and potential biological roles of these DNA modifications in mammals.


Natal and neonatal teeth: a review and case series.
Natal and neonatal teeth are a relatively rare but well-documented phenomenon, with the majority being prematurely erupted teeth of the normal primary dentition. Related complications include feeding issues, traumatic lingual ulceration and risk of aspiration. We present three clinical cases referred to the Paediatric Dentistry Department at Guy's and St Thomas' NHS Foundation Trust and their management. Treatment choice is based on individual assessment of each patient and options include monitoring, smoothing of the teeth or extraction. General dental practitioners should be able to diagnose natal and neonatal teeth and provide initial management in primary care, with referral to secondary care services in more complex cases or those which are likely to require extraction.


Comparison of novel pro-BNP(1-108) and standard BNP assays in heart failure patients.
Heart failure (HF) progression and outcomes reflect activation of multiple neurohormonal systems. Which biomarkers reflecting these systems contribute incremental information remains unclear. The aim of this study was to determine if serial measurements of pro-BNP(1-108) separately, in combination with standard assay BNP, or with troponin T (cTnT) would enhance risk stratification in ambulatory HF patients. A cohort of 187 Class III-IV HF patients was prospectively studied. Blood was collected every 3 months over 2 years for biomarker analysis [pro-BNP(1-108), standard assay BNP, troponin T (cTnT)] in relation to the primary endpoint of death or cardiac transplantation. Univariate categorical and continuous variable analyses of single-sample and time-dependent serial values of pro-BNP(1-108) and BNP demonstrated that elevations in both biomarkers were associated with increased risk of death/transplantation. Multivariate analysis of serial measurements adjusted for cTnT revealed cTnT as the independent marker of risk. Combined elevations of either pro-BNP(1-108) or BNP with cTnT, however, were the most significant predictors of outcome. Circulating levels of pro-BNP(1-108) appear to be comparable to mature BNP in ambulatory HF out-patients. Elevated levels of pro-BNP(1-108) or BNP identified by serial monitoring similarly predict events. A strategy of serial monitoring of either pro-BNP(1-108) or BNP alone or particularly in combination with cTnT can serve a valuable role in detecting higher-risk HF patients.


A Qualitative Examination of Situational Risk Recognition Among Female Victims of Physical Intimate Partner Violence.
Little is known about intimate partner violence (IPV) victims' situational risk recognition, defined as the ability to identify situational factors that signal imminent risk of victimization. Using semi-structured interviews, qualitative data were collected from a community sample of 31 female victims of IPV episodes involving substance use. Thirteen themes were identified, the most prevalent being related to the partner's verbal behavior, tone of voice, motor behavior, alcohol or drug use, and facial expression. Participants reporting at least some anticipation of physical aggression (61.3% of the sample) tended to identify multiple factors (M = 3.47), suggesting numerous situational features often contribute to situational risk recognition.


Social media for patient engagement.
Who better to serve as "Dr. Google" than an actual doctor? Patients often present with a list of symptoms and turn to their favorite search engine to understand their constellation of symptoms. In this editorial, we attempt to address the following key elements in surgeons' use of social media (#SoMe4Surgery) as a tool for patient engagement: marketing, demystifying and differentiating the surgical specialty, a fast track to the latest specialty-specific guidelines and recommendations, and combatting medical misinformation. The increased social media presence in the medical space can be used to improve health literacy and simplify the navigational process of one's healthcare journey. These platforms can humanize physicians, make them more accessible, and bridge the gap that sometimes exists, preventing patients from moving to their next step in care due to fear. The extent of social media use in healthcare far surpasses this brief discussion, and it is up to the individual user to exercise the appropriate uses and responsibilities regarding patient communication.


ADRB2 polymorphisms in allergic asthma in Han Chinese children.
Single-nucleotide polymorphisms (SNPs) in the human β2 adrenergic receptor (ADRB2) gene have been linked to pathogenesis of and treatment responses in asthma. In China, where asthma is common, little information exists regarding ADRB2 variants and their effects on asthma. The current study sought to investigate the relationship between variations in ADRB2 and childhood asthma. Blood samples were collected from 298 pediatric asthma cases treated in our hospital from July 2013 to September 2014; 304 samples were collected from healthy children for a control group. Six loci (at base positions -47, 79, -2387, 46, 523, and 491) of ADRB2 were genotyped using the TaqMan probe assay; SHEsis was used to determine haplotypes. Allele frequencies and genotype distributions were compared between groups using chi square and t tests. No significant differences in genotype or allele frequencies were found between the groups for the polymorphic loci -2387 bp (T>C), 46 bp (G>A), and 523 bp (C>A) (p > 0.05). However, genotype frequencies for the ADRB2 SNPs at -47 bp (C>T) and 79 bp (G>C) differed significantly between asthma and control groups (p < 0.05). Further, linkage disequilibrium was found between these 2 SNPs (D' = 0.990, r(2) = 0.962), as well as between SNPs at 46 and 523 bp (D' = 0.985, r(2) = 0.607). Finally, of the 4 haplotypes analyzed in these samples (haplotypes III, IV, IX, and XI), the frequency of haplotype III was significantly lower in the asthma group than the control group (p < 0.05; odds ratio [OR] = 0.72; 95% confidence interval [CI], 0.48 to 0.97). Variations of ADRB2 at base positions -47 (C>T) and 79 (G>C), as well as haplotype III, may contribute to susceptibility to childhood asthma.


Antiproliferative activity of meso-substituted BODIPY photocages: Effect of electrophiles vs singlet oxygen.
A series of BODIPY compounds with a methylphenol substituent at the meso-position and halogen atoms on the BODIPY core, or OCH3 or OAc substituents at the phenolic moiety was synthesized. Their spectral and photophysical properties and the photochemical reactivity upon irradiation in CH3OH were investigated. The molecules with the phenolic substituent at the meso-position undergo more efficient photo-methanolysis at the boron atom, while the introduction of the OCH3 group at the phenolic moiety changes the reaction selectivity towards the cleavage at the meso-position. The introduction of the halogen atoms into the BODIPY increases the photo-cleavage reaction efficiency, as well as the ability of the molecules to sensitize oxygen and form reactive oxygen species (ROS). The efficiency of the ROS formation was measured in comparison with that of tetraphenylporphyrin. The antiproliferative effect of BODIPY molecules was investigated against three human cancer cell lines MCF-7 (breast carcinoma), H460 (lung carcinoma), HCT116 (colon carcinoma), and two non-cancer cell lines, HEK293T (embryonic kindey) and HaCaT (keratinocytes), with the cells kept in the dark or irradiated with visible light. For most of the compounds a modest or no antiproliferative activity was observed for cells in the dark. However, when cells were irradiated, a dramatic increase in cytotoxicity was observed (more than 100-fold), with IC50 values in the submicromolar concentration range. The enhancement of the cytotoxic effect was explained by the formation of ROS, which was studied for cells in vitro. However, for some BODIPY compounds, the effects due to the formation of electrophilic species (carbocations and quinone methides, which react with biomolecules) cannot be disregarded. Confocal fluorescence microscopy images of H460 cells and HEK293T show that the compounds enter the cells and are retained in the cytoplasm and membranes of the various organelles. When the cells treated with the compounds are irradiated, photo-processes lead to cell death by apoptosis. The study performed is important because it provides bases for the development of novel photo-therapeutics capable of exerting photo-cytotoxic effects in both oxygenated and hypoxic cells.


Therapeutic potential of lectins in the treatment of breast cancer: A review.
Breast cancer is one of the most common malignancies and the leading cause of cancer-related deaths in women. There are 3 major subtypes of breast cancer that are distinguished by expression of estrogen or progesterone receptors and ERBB2 gene amplification. The 3 subtypes have different risk profiles and treatment strategies. Abnormal glycosylation is thought to play an important role in the development of the tumorigenic and metastatic phenotype of breast cancer and resistance to therapy. They may also be a potentially attractive target for breast cancer treatment. Proteins such as lectins, a family of carbohydrate-binding proteins found in a variety of organisms from viruses to humans, can specifically interact with abnormally glycosylated carbohydrate residues in cancer cells and induce cytotoxic effects. In recent years, there has been a growing number of research addressing studies demonstrating their antitumorigenic and antimalignant effects. This review summarizes recent findings on lectins from plants, animals, fungi, and bacteria that are potentially therapeutic agents against breast cancer and outlines the basis of their mechanism of action.


Nanofiltration as a robust method contributing to viral safety of plasma-derived therapeutics: 20 years' experience of the plasma protein manufacturers.
Nanofiltration entails the filtering of protein solutions through membranes with pores of nanometric sizes that have the capability to effectively retain a wide range of viruses. Data were collected from 754 virus validation studies (individual data points) by Plasma Protein Therapeutics Association member companies and analyzed for the capacity of a range of nanofilters to remove viruses with different physicochemical properties and sizes. Different plasma product intermediates were spiked with viruses and filtered through nanofilters with different pore sizes using either tangential or dead-end mode under constant pressure or constant flow. Filtration was performed according to validated scaled-down laboratory conditions reflecting manufacturing processes. Effectiveness of viral removal was assessed using cell culture infectivity assays or polymerase chain reaction (PCR). The nanofiltration process demonstrated a high efficacy and robustness for virus removal. The main factors affecting nanofiltration efficacy are nanofilter pore size and virus size. The capacity of nanofilters to remove smaller, nonenveloped viruses was dependent on filter pore size and whether the nanofiltration process was integrated and designed with the intention to provide effective parvovirus retention. Volume filtered, operating pressure, and total protein concentration did not have a significant impact on the effectiveness of virus removal capacity within the investigated ranges. The largest and most diverse nanofiltration data collection to date substantiates the effectiveness and robustness of nanofiltration in virus removal under manufacturing conditions of different plasma-derived proteins. Nanofiltration can enhance product safety by providing very high removal capacity of viruses including small non-enveloped viruses.


Antiproliferative and apoptotic effects of selective phenolic acids on T47D human breast cancer cells: potential mechanisms of action.
The oncoprotective role of food-derived polyphenol antioxidants has been described but the implicated mechanisms are not yet clear. In addition to polyphenols, phenolic acids, found at high concentrations in a number of plants, possess antioxidant action. The main phenolic acids found in foods are derivatives of 4-hydroxybenzoic acid and 4-hydroxycinnamic acid. This work concentrates on the antiproliferative action of caffeic acid, syringic acid, sinapic acid, protocatechuic acid, ferulic acid and 3,4-dihydroxy-phenylacetic acid (PAA) on T47D human breast cancer cells, testing their antioxidant activity and a number of possible mechanisms involved (interaction with membrane and intracellular receptors, nitric oxide production). The tested compounds showed a time-dependent and dose-dependent inhibitory effect on cell growth with the following potency: caffeic acid > ferulic acid = protocatechuic acid = PAA > sinapic acid = syringic acid. Caffeic acid and PAA were chosen for further analysis. The antioxidative activity of these phenolic acids in T47D cells does not coincide with their inhibitory effect on tumoral proliferation. No interaction was found with steroid and adrenergic receptors. PAA induced an inhibition of nitric oxide synthase, while caffeic acid competes for binding and results in an inhibition of aryl hydrocarbon receptor-induced CYP1A1 enzyme. Both agents induce apoptosis via the Fas/FasL system. Phenolic acids exert a direct antiproliferative action, evident at low concentrations, comparable with those found in biological fluids after ingestion of foods rich in phenolic acids. Furthermore, the direct interaction with the aryl hydrocarbon receptor, the nitric oxide synthase inhibition and their pro-apoptotic effect provide some insights into their biological mode of action.


Ulerythema ophryogenes with multiple congenital anomalies.
Ulerythema ophryogenes, a rare dermatologic disorder characterized by inflammatory keratotic facial papules that may result in scars, atrophy, and alopecia, can occur in association with other congenital anomalies. A case reported here was accompanied by an unusual facies, developmental delay, central nervous system abnormalities, dental anomalies, and undescended testes. There was no response of the cutaneous lesions to topical keratolytics, topical tretinoin, or a short course of oral isotretinoin.


Access and benefit-sharing: what indicators to measure 'success'?
We examine challenges with measuring 'success' in access and benefit-sharing (ABS) of biological resources. We note a lack of indicators and draw on Pacific patent landscaping, ABS case studies, and research permit figures to highlight that ABS systems are functioning somewhat, although they are often not meeting expectations.


Modeling the effects of the governmental responses to COVID-19 on transit demand: The case of Athens, Greece.
Short-term demand forecasting is essential for the public transit system, allowing for effective operations planning. This is especially relevant in the highly uncertain environment created by the SARS‑CoV‑2 pandemic. In this paper, we attempt to develop accurate prediction models of transit ridership in Athens, Greece, using Autoregressive Fractional Integrated time series models enhanced with SARS‑CoV‑2-related exogenous variables. The selected exogenous variables are, from the one hand, the ratio of weekly SARS‑CoV‑2 infections over the infections 3 weeks before (capturing the dynamics of the pandemic, as a proxy for fear of transmitting the disease while commuting), and from the other hand, an index of the stringency of the government's SARS‑CoV‑2-related measures and regulations. The developed ARFIMAX models have been fitted separately on bus and metro ridership data and wield comparable and statistically significant results. In both models, the exogenous variables prove to be statistically significant and their values are intuitive, suggesting a linear interrelation between them and transit ridership.


Early gastric cancer: Report of 58 cases.
BACKGROUND: This retrospective study was carried out to review our surgical experience and to define the clinicopathologic profile of early gastric cancer in a Western country with one of the highest incidences in the world.METHODS: Fifty-eight patients who had gastric surgery for early gastric cancer were included in this study.RESULTS: The incidence of early gastric cancer was 13.9% of the patients with resected gastric cancer (58/416). The mean age of these 58 patients at diagnosis was 56.8 +/- 12.3 years (range, 30-81 years) and the male: female ratio was 2.4 : 1. The most common presenting symptom was epigastric pain (52.4%). All patients were treated by surgical resection. Tumors were typically located in the antrum (72.4%), with a predominance of lesser curvature lesions (89.7%). Macroscopically, the majority of the lesions (63.8%) were excavated (types IIc and III). Thirty tumors were intramucosal and 28 extended into the submucosa. Thirty were of the intestinal type and 28 of the diffuse type. The rate of regional lymph node metastasis was 10.4%. The overall 5-year survival rate was 93.9%.CONCLUSIONS: The excellent response to surgical resection of early gastric cancer reported by Japanese authors is reproducible in Western countries even in the presence of regional lymph node metastasis. For this reason an aggressive surgical approach should be taken for all early gastric cancer.


Low concentration quaternary ammonium compounds promoted antibiotic resistance gene transfer via plasmid conjugation.
During the pandemic of COVID-19, the amounts of quaternary ammonium compounds (QACs) used to inactivate the virus in public facilities, hospitals and households increased, which raised concerns about the evolution and transmission of antimicrobial resistance (AMR). Although QACs may play an important role in the propagation of antibiotic resistance gene (ARGs), the potential contribution and mechanism remains unclear. Here, the results showed that benzyl dodecyl dimethyl ammonium chloride (DDBAC) and didecyl dimethyl ammonium chloride (DDAC) significantly promoted plasmid RP4-mediated ARGs transfer within and across genera at environmental relevant concentrations (0.0004-0.4 mg/L). Low concentrations of QACs did not contribute to the permeability of the cell plasma membrane, but significantly increased the permeability of the cell outer membrane due to the decrease in content of lipopolysaccharides. QACs altered the composition and content of extracellular polymeric substances (EPS) and were positively correlated with the conjugation frequency. Furthermore, transcriptional expression levels of genes encode for mating pairing formation (trbB), DNA replication and translocation (trfA), and global regulators (korA, korB, trbA) are regulated by QACs. And we demonstrate for the first time that QACs decreased the concentration of extracellular AI-2 signals, which was verified to be involved in regulating conjugative transfer genes (trbB, trfA). Collectively, our findings underscore the risk of increased disinfectant concentrations of QACs on the ARGs transfer and provide new mechanisms of plasmid conjugation.


Active immunization against spontaneous tumors in mice.
The incidence of spontaneous tumors was studied in a group of 136 female mice and in another group of 138 females after a sublethal dose of total body irradiation. Of the nonirradiated mice 10.2% developed mammary tumors, and 8% developed lung tumors. Of the irradiated mice 19.5% developed mammary tumors, 21.7% ovary tumors, 24.5% lung tumors, and 7.9% tumors in other organs. A vaccine was prepared for only mammary and ovary tumors through an original technique. The results showed a signficantly lower incidence of tumors in another two groups of mice that were immunized: in 80 nonirradiated vaccinated femal mice, mammary tumors decreased from 10.2% to 2.5%, and in 78 irradiated and vaccinated female mice, mammary tumors decreased from 19.5% to 8.9% and ovary tumors from 21.7% to 3.8%. Lung tumors also decreased in the latter group, suggesting a common factor protecting the immunized mice.


Stereoselectivity of fructose-1,6-bisphosphate aldolase in Thermus caldophilus.
It was recently established that fructose-1,6-bisphosphate (FBP) aldolase (FBA) and tagatose-1,6-bisphosphate (TBP) aldolase (TBA), two class II aldolases, are highly specific for the diastereoselective synthesis of FBP and TBP from glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP), respectively. In this paper, we report on a FBA from the thermophile Thermus caldophilus GK24 (Tca) that produces both FBP and TBP from C(3) substrates. Moreover, the FBP:TBP ratio could be adjusted by manipulating the concentrations of G3P and DHAP. This is the first native FBA known to show dual diastereoselectivity among the FBAs and TBAs characterized thus far. To explain the behavior of this enzyme, the X-ray crystal structure of the Tca FBA in complex with DHAP was determined at 2.2A resolution. It appears that as a result of alteration of five G3P binding residues, the substrate binding cavity of Tca FBA has a greater volume than those in the Escherichia coli FBA-phosphoglycolohydroxamate (PGH) and TBA-PGH complexes. We suggest that this steric difference underlies the difference in the diastereoselectivities of these class II aldolases.


Short-Term Changes in Posture and Pain of the Neck and Lower Back of Women Undergoing Lipoabdominoplasty: A Case Series Report.
The purpose of this study was to analyze short-term variations in posture and intensity of neck and lower back pain in women undergoing lipoabdominoplasty. This prospective case series study involved 17 women (age 43 ± 12 years, presurgical body mass index 27.0 ± 3.7 kg/m2). Participants were assessed preoperatively (T0) and at 15 (T15) and 30 days (T30) after surgery for clinical data (number of pregnancies, number of deliveries, presurgical body mass), neck and lower back angles calculated by photogrammetry, and pain intensity by numeric pain rating scale. Postoperative complications were assessed at T15 and T30. After adjusting for age and presurgical body mass index, there was an increase in forward head position in T15 and a return by T30 (marginal R2 = 0.411). The lower back showed an increase in flexion at T15 and return by T30 (marginal R2 = 0.266). No statistical evidence of significance was observed for changes in the intensity of neck (P > .355) or lower back (P > .293) pain. Complications were mild and common at T15; most of them resumed at T30. A transient, nonlinear compensatory change in neck and lower back lordosis was observed 15 days after lipoabdominoplasty, with almost full recovery in the short term (30 days). No systematic change in pain intensity was observed within this period. Postsurgical complications were mild and common, and most of them resumed shortly after surgery.


Prevalence of incontinence by race and ethnicity of older people admitted to nursing homes.
While admissions of minorities to nursing homes (NHs) are increasing and prevalence of incontinence in NHs remains high, little is known about incontinence among racial-ethnic groups of NH admissions other than blacks. The purpose of this study was to describe the prevalence of incontinence among older adults admitted to NHs by race/ethnicity at three levels of measurement: individual resident, NH, and Census division. Cross-sectional and descriptive. Admissions of persons age 65 or older to 1 of 457 NHs of a national, for-profit chain over 3 years 2000-2002 (n = 111,640 residents). Data sources were the Minimum Data Set v. 2.0 and 2000 US Census. Prevalence of the following definitions of incontinence was analyzed: Only Urinary Incontinence (UI), Only Fecal Incontinence (FI), Dual Incontinence (DI; UI and FI), Any UI (UI with or without FI), Any FI (FI with or without UI), and Any Incontinence (UI and/or FI and/or DI). Asian patients, black patients, and Hispanic patients had a higher prevalence of Any Incontinence (67%, 66%, and 58%, respectively) compared to white patients (48%) and American Indian patients (46%). At the NH level, all prevalence measures of incontinence (except Only UI) appear to trend in the opposite direction from the percentage of NH admissions who were white. Among Asian and white patients, there was a higher prevalence of all types of incontinence in men compared with women except for Only UI. Among Census divisions, the prevalence of all types of incontinence, except Only UI, was lowest in the 2 divisions with the highest percentage of white admissions to their NHs. NHs admitting more racial/ethnic minorities may be faced with managing more incontinence and needing additional staffing resources. The association of the prevalence of most types of incontinence with the race/ethnicity of NH admissions at all levels of measurement lend support to the growing evidence that contextual factors beyond individual resident characteristics may contribute to NH differences.


Factors Associated With Loss of Follow-Up in Transgender Patients Receiving Vocal Therapy.
Optimal vocal care for transgender patients necessitates regular follow-up. Factors associated with loss of follow-up in voice patients have never been investigated. In this study, we report a case series of transgender patients seeking vocal care at our institution and compare those who were and were not lost to follow-up. Charts of transgender patients diagnosed with gender dysphoria who sought vocal care at our institution from January 2018 through May 2022 were reviewed. A chronological timeline of each patient's care at our vocal clinic was recorded. Loss of follow-up was defined as instances in which patients were not yet satisfied with their vocal outcomes and expressed interest in scheduling a subsequent visit but had not yet done so. Logistic regressions were performed to identify factors associated with loss of follow-up. Of 73 patients identified, 59 (80.8%) were assigned male at birth, and 72 (98.6%) were non-Hispanic White. Loss of follow-up occurred in 35 (47.9%) patients. Patients who received vocal surgery were significantly less likely to be lost to follow-up (OR: 0.16 (0.03, 0.79); p = 0.03). The availability of telemedicine options for vocal care was protective against loss of follow-up (OR: 0.09 (0.02, 0.44); p = 0.003). Patients who received other non-voice gender-affirming treatments concomitant to their vocal care were more likely to be lost to follow-up (OR: 4.44 (1.35, 14.59); p = 0.01). Loss of follow-up in transgender patients receiving vocal care is common. Providing telemedicine options and encouraging patients to complete vocal care prior to or after receiving other non-voice gender-affirming treatments may help increase rates of follow-up. 4 Laryngoscope, 133:3061-3067, 2023.


Molecular and functional characterization of a putative PA28γ proteasome activator orthologue in Schistosoma mansoni.
PA28γ is a proteasome activator involved in the regulation of the cellular proliferation, differentiation and growth. In the present study, we identified and characterized a cDNA from Schistosoma mansoni exhibiting significant homology to PA28γ of diverse taxa ranging from mammals (including humans) to simple invertebrates. Designated SmPA28γ, this transcript has a 753bp predicted ORF encoding a protein of 250 amino acid residues. Alignment of SmPA28γ with multiple PA28γ orthologues revealed an average similarity of ~40% among the investigated organisms, and 90% similarity with PA28γ from Schistosoma japonicum. In addition, phylogenetic analysis demonstrated a close linkage between SmPA28γ to its sister group that contains well-characterized PA28γ sequences from Drosophila spp., as well as sharing the same branch with PA28γ from S. japonicum. Gene expression profiling of SmPA28γ using real-time quantitative PCR revealed elevated steady-state transcript levels in the eggs, miracidia and paired adult worms compared to other stages. In parallel with gene expression profiles, an affinity-purified anti-SmPA28γ antibody produced against recombinant protein exhibited strongest reactivity in Western blot analyses to endogenous SmPA28γ from miracidia, sporocysts and paired adult worms. Given its known regulatory function in other organisms, we hypothesized that the high level of SmPA28γ transcript and protein in these stages may be correlated with an important role of the PA28γ in the cellular growth and/or development of this parasite. To address this hypothesis, miracidia were transformed in vitro to sporocysts in the presence of SmPA28γ double-stranded RNAs (dsRNAs) and cultivated for 4 days, after which time steady-state transcript and protein levels, and phenotypic changes were evaluated. SmPA28γ dsRNA treatment resulted in gene and protein knockdown of ~60% and ~80%, respectively, which were correlated with a significant decrease in larval length compared to its controls. These findings are consistent with a putative role of SmPA28γ in larval growth/development of the S. mansoni.


Brain imaging, genetics and emotion.
This paper reviews the published evidence on genetically driven variation in neurotransmitter function and brain circuits involved in emotion. Several studies point to a role of the serotonin transporter promoter polymorphism in amygdala activation during emotion perception. We also discuss other polymorphisms (e.g. the COMT val158met polymorphism, tryptophan hydroxylase-2 -703 G/T) and putative effects on affective processing in cortical and limbic regions. A different line of research concerns studies with genetic disorders. Although at a less fine-grained level, studies with individuals with aneuploidies of the X chromosome (Turner syndrome and Klinefelter syndrome), who display impairments in emotion processing, have resulted in new insights and hypotheses with regard to X chromosomal influences on brain systems supporting cognition and emotion. These have also implicated a key role for the amygdala. Integration of the emerging evidence, suggests that the study of polymorphisms using brain imaging can potentially elucidate biological pathways and mechanisms contributing to individual differences in brain circuits that may bias behavior and affect risk for psychiatric illness.


Ivosidenib: First Global Approval.
Ivosidenib (Tibsovo®) is a small molecule, orally available inhibitor of mutated cytosolic isocitrate dehydrogenase 1 (IDH1) that is being developed by Agios Pharmaceuticals for the treatment of cancer in patients with IDH1 mutations. The mutated form of the IDH1 enzyme produces a metabolite, 2-hydroxyglutarate (2-HG), which is thought to play a role in the formation and progression of acute myeloid leukaemia (AML), gliomas and other cancers. Elevated 2-HG levels interfere with cellular metabolism and epigenetic regulation, thereby contributing to oncogenesis. Ivosidenib targets the IDH1 metabolic pathway to prevent a build-up of the oncometabolite 2-HG. This article summarizes the milestones in the development of ivosidenib leading to this first approval in the USA for the treatment of patients with relapsed or refractory AML with a susceptible IDH1 mutation. Clinical development for AML, cholangiocarcinoma, glioma, myelodysplastic syndromes and solid tumours is ongoing worldwide.


Characterization of variations in rabbit hepatic progesterone 21-hydroxylase activity by serial biopsy.
Earlier work has shown that the 21-hydroxylation of progesterone in the hepatic microsomal fraction of outbred New Zealand White rabbits varies over a 10-fold range. To determine whether the differences in 21-hydroxylase activity were due to a transient inductive effect, livers from a group of 28 rabbits were serially biopsied at least three times over a minimum period of two months. Both progesterone 21- and 16 alpha-hydroxylase activities were determined in the post-8700g supernatant of homogenates prepared from these biopsy samples. A substantial variability in both the 21- and 16 alpha-hydroxylase activity was observed for serial biopsy samples from individual rabbits. Each animal was found, however, to maintain relatively constant ratios of 21/16 alpha-hydroxylase activity throughout the course of the study. Previous studies have indicated that the 21-hydroxylase activity does not correlate with the 16 alpha-hydroxylase activity and that the 21-hydroxylase phenotype could be determined from the ratio of these activities. On the basis of this ratio, two groups of animals could be distinguished in the present study. Approximately 25% of the animals exhibited an elevated 21/16 alpha-hydroxylase ratio (greater than 1.5), the remainder were below this level. Furthermore, the expression of elevated levels of the 21-hydroxylase activity were found to be consistent within this subpopulation suggesting that a transient inductive effect is not responsible for the differences in 21-hydroxylase activity among populations of outbred New Zealand White rabbits. This study demonstrates the determination of the hepatic enzymatic phenotype while maintaining the animal for long periods of time and for subsequent investigations.


All about that Amide Bond: The Sixth Chemical Protein Synthesis (CPS) Meeting.
Endless potential: The sixth Chemical Protein Synthesis Meeting, held recently in St. Augustine, Florida, showed the potential of peptide and protein chemistry when applied toward understanding and controlling complex biological processes. This report highlights the diverse and cutting-edge protein chemistry presented at the meeting.


[Current views on vision of mammals].
In the review, research data are presented on mammals' vision including visual pigments, color and contrast vision, and visual behaviour in different species. It is shown that in course of evolution mammals were gradually losing the elements of daylight cone vision system that are typical of other vertebrates. In monotremes, visual pigments SWS2 (cone blue-sensitive 2) and MWS/LWS (green/red-sensitive) are still present, as well as rod RH1. Theria, except some primates, also have two cone visual pigments: SWS1 (ultraviolet/violet or blue-sensitive 1) and MWS/LWS along with rod RH1. Humans and some other higher primates evolved the new visual pigment, MWS, and acquired trichromatic vision. Marine mammals (cetaceans and pinnipeds) and some species of other orders have lost also the visual pigment SWS1, probably due to specificity of processing the information received by these cones. Current view on mammals' vision with two cone pigments and rods is presented. Data on maximum spectral sensitivity of visual pigments in different species and orders are given along with data on spatial contrast sensation. High visual acuity has been acquired by ungulates, artiodactyls, and primates, while the highest one--by humans with their specialized fovea.


Solitary fibrous tumor in the maxillary sinus treated by endoscopic medial maxillectomy.
Solitary fibrous tumor (SFT) is an uncommon neoplasm that usually arises from the pleura. Recently, SFTs have been reported in the head and neck area. SFTs of the nasal cavity and paranasal sinuses are extremely rare, with only 24 cases reported in the English literature. We describe an SFT that arose from the left maxillary sinus and extended to the nasal cavity. The tumor was removed by endoscopic medial maxillectomy, which permitted monobloc excision of the lesion. The patient is without the evidence of the disease 12 months after surgery.


Mechanical and radiation shielding characterization of W-based alloys for advanced nuclear unit.
The paper aims to investigate the mechanical and radiation shielding properties of two tungsten-based alloys manufactured by powder technology; their features when compared with two standard stainless steel grades for advanced nuclear applications. Multiple measurements were performed to characterize the alloys' structural and mechanical properties. XRD analysis and average surface roughness measurements showed the crystalline and morphological structure of the alloys. Surface microhardness added to the abrasive wear analysis showed the final wear resistance of the selected alloys. In addition, the shielding features against gamma and fast neutrons radiation were calculated. The superior characteristics of W-based alloys manufactured by powder technology make them suitable to be used in advanced nuclear power units.


Airway management in Nager Syndrome.
Nager acrofacial dysostosis is a rare congenital syndrome characterized by malformed mandibulofacial structures and pre-axial upper limbs. Trismus and glossoptosis from mandibular abnormalities predisposes infants to life-threatening respiratory distress. A case of a Nager Syndrome mother delivering a similarly afflicted fetus is presented, with approaches to maintaining both tenuous airways described. Distinguishing this condition from similar syndromes is critical for care and prognosis.


[p16 gene deletion and point mutation in highly purified fresh breast neoplasm].
To study the form and frequency of p16 gene deletion and point mutation in human breast neoplasm and the effective detection. Cell culture was made using repeat-adhering method to purify human breast neoplasm cells and PCR-SSCP analysis in 14 highly purified fresh breast neoplasm, 14 fresh none-purified specimens, 27 paraffin-embedded specimens and corresponding normal tissues beside neoplasms. The rate of p16 gene deletion and point mutation was 42.9% (6/14) in the highly purified group, in which exon 1st - 3rd, showed homozygous deletion (5 cases) and exon 2nd showed mutation (1 case). The rate of p16 gene mutation in the other three groups was 7.1%, 7.4% and 4.9%. The detection rate of mutation was significantly higher in the highly purified group than in the other three groups (P < 0.01), but it was not significantly different in the other three groups (P > 0.05). p16 gene deletion and point mutation exist in primary breast cancer. Homozygous deletion and small fragment deletion may be an important mechanism of inactivation in human breast neoplasm. Purified cancer cells will enhance the detection rate.


Mutation of cysteine 254 facilitates the conformational changes accompanying the interconversion of persulfide-substituted and persulfide-free rhodanese.
Mutants of rhodanese (EC 184.108.40.206) that substitute Ser for Cys-254 and/or Cys-263, i.e. C254S, C263S, and the double mutant C254/263S, were compared with the wild-type enzyme to test the hypothesis that the persulfide formation to give sulfur-substituted rhodanese (ES) during catalysis can exert a stabilizing influence on the global structure of the protein. All the ES forms were quite refractory toward limited tryptic digestion. Extensive digestion was observed only in the persulfide-free forms (E) of mutants having substitutions of Ser for Cys-254 (C254/263S and C254S). Limited proteolysis of C254/263S produced a species on SDS gels at approximately 21 kDa that was proteolyzed further to give a slightly smaller product. Amino acid sequencing, together with mass spectrometry, indicated that these two components had the same N-terminal sequence as wild-type rhodanese and that they resulted from cleavage in the C-terminal domain, first at residues Arg-186 or Arg-182 and subsequently at Arg-175 or Lys-174. In addition to increased proteolytic susceptibility, the conversion from ES to E of C254/263S was accompanied by increased hydrophobic exposure and increased quenching of the intrinsic protein fluorescence by acrylamide. The substitution of Ser for Cys-254, within the helix suggested to be involved in stabilizing the persulfide bond in ES, seems to promote the formation of flexible conformations of sulfur-free rhodanese. In keeping with this model, C254/263S shows a marked increase in the hysteresis that is observed in rhodanese catalysis at pH 7 and high ionic strength. These results can be understood in terms of a model, suggesting that there is mutual stabilization of the protein structure and the persulfide bond in the ES form of rhodanese.


Endpoints for agents that slow tumor growth.
The endpoints of confirmed response and progression are widely used in oncology clinical trials. These endpoints originated at a time when agents used to treat cancer were primarily cytotoxic. Increasingly agents that are cytostatic are being investigated in combination with agents that are cytotoxic. Since tumor growth rates often depend on the volume of the tumor, combining cytotoxic agents that reduce tumor volume with cytostatic agents may mask the activity of the cytostatic agent. This paper explores the sensitivity of time to progression/progression free survival (TTP/PFS) as an endpoint for evaluating the efficacy of cytostatic drugs when combined with cytotoxic agents. Mathematical models of tumor growth are used to describe tumor growth over time. The models account for the impact of chemotherapy and an agent that slows tumor growth in the context of the Gompertzian growth kinetics. We use a clinical trial of an angiogenesis inhibitor in metastatic breast cancer as a motivating example. We demonstrate that the endpoint TTP/PFS may not be sensitive to the effects of active cytostatic agents when they are combined with chemotherapy, and measuring time to regrowth would be more sensitive to the activity of a cytostatic agent. We conclude that an active cytostatic agent may not appear effective when combined with chemotherapy and evaluated with TTP/PFS in a clinical trial.


Lung microbiome and transcriptome reveal mechanisms underlying PM2.5 induced pulmonary fibrosis.
Airborne fine particulate matter (PM2.5) is considered to be a risk factor for lung fibrosis, and therefore, it has attracted public attention due to its various physicochemical features and its adverse effects on health. However, little remains to be known regarding the mechanism of PM2.5-induced pulmonary fibrosis. The lung microbiota may be a potential factor involved in the adverse outcomes of pulmonary fibrosis. Meanwhile, miRNAs are thought to be key regulators that participate in the complex interplay between the host and the microbiota. Hence, to investigate the potential mechanisms of pulmonary fibrosis, and to explore the impact of PM2.5-induced alterations in miRNAs and the lung microbiota and possible interaction patterns in mice models, we took advantage of 16S rDNA gene sequencing, miRNAs sequencing (miRNAs-Seq), and mining of public databases profiling. The results of 16S rDNA analysis showed that PM2.5 interfered with the microbial community composition, resulting in Proteobacteria becoming an additional dominant phylum. In addition, differentially expressed miRNAs were enriched in HIF-1 signaling, the IL-17 signaling, as well as Th17 cell differentiation pathways, which are closely related to microbial functional pathways. Significantly, a target miRNA, miR-149-5p, may be a key factor triggering the MAPK signal pathway related to pulmonary fibrosis and disturbing the homeostasis of lung bacterial flora. These results indicate that PM2.5 may lead to interaction between lung microbiota dysbiosis and an imbalance of miRNA levels to form a vicious cycle that promotes lung fibrogenesis. The current study provides new insights into the progression of pulmonary fibrosis.


A reporter system using a flow cytometer to detect promoter/enhancer activity in lymphoid cell lines.
We have devised an experimental system using a flow cytometer to examine the promoter/enhancer activity of DNA fragments in human lymphoid cell lines. Murine CD8 alpha gene cDNA used as a reporter gene was inserted in the reporter constructs under the control of various promoter/enhancers. Furthermore, the Epstein-Barr virus (EBV) OriP, which supports a high transient expression, was also included in the reporter constructs. Cell lines expressing EBV nuclear antigen-1 (EBNA-1) were transfected with the reporter constructs by electroporation. The expression of the reporter gene was measured by a flow cytometric analysis. This experimental system is quite simple and may be especially useful for the analysis of transcriptional elements functioning in lymphocytes.


Validity and reliability of the (adjusted) Impact on Participation and Autonomy questionnaire for social-support populations.
Decentralisation of social support and budget cuts spurred interest in outcome-oriented payment systems in the Netherlands. Hence, measurement of relevant outcomes, such as self-reliance and participation, is needed. The Impact on Participation and Autonomy (IPA) questionnaire for rehabilitation clients was adapted for social support, called IPA-MO, and its validity and reliability were tested among social support clients in eight municipalities in 2014 and 2016. The total research sample comprised of 4120 persons. Homogeneous subgroups were distinguished based on 1) disability and 2) age. Exploratory factor analysis (PCF) was used to identify domains for IPA-MO. Model fit was assessed with Confirmatory Factor Analysis (CFA) using structural equation modelling. PCF revealed that the IPA-MO model consists of all five original IPA domains: Autonomy indoors, Family role, Autonomy outdoors, Social life and relations, and Work and education. As a result of new items added, a new, sixth domain was developed: Financial autonomy. Due to high non-response on Work & education, construct validity was first tested for a five-domain IPA-MO model. The composition of the IPA-MO domains showed slight differences: the item on 'mobility indoor' shifted from Autonomy indoors (IPA) to Family Role in IPA-MO. The item on reciprocity shifted from Social Life and relations (IPA) to Autonomy outdoors (IPA-MO). Internal reliability was confirmed for all domains (Cronbach's alpha >.80). CFA showed acceptable construct validity of the five-domain IPA-MO model for the social support population (CFI .936, TLI .925, SRMR .051), all age groups and most disability-based groups. Construct validity including Work & education was tested for 234 participants. Then, PCF revealed six domains and the model fit was acceptable (CFI .915, TLI .903, SRMR .067). IPA-MO is a valid and reliable instrument to assess outcomes of social support. Further research on the domain Financial autonomy is needed. Social-support clients are numerous and dispersed and, in spite of the best intentions, hard to involve widely in policy processes. A valid outcome measure offers municipalities possibilities to gain insight in social costs and benefits of new policies. Outcome measurement also allows to contract bundled-services of providers, thereby changing the incentives for providers from increasing production to much needed innovation. Taking the perceptions of autonomy and participation of social-support clients as the acid test for the effectiveness of social support policies, may prove a serious game-changer in politics.


First Principles Study on the Interaction Mechanisms of Water Molecules on TiO₂ Nanotubes.
The adsorption properties of water molecules on TiO₂ nanotubes (TiO₂NT) and the interaction mechanisms between water molecules are studied by first principles calculations. The adsorption preferences of water molecules in molecular or dissociated states on clean and H-terminated TiO₂NT are evaluated. Adsorption of OH clusters on (0, 6) and (9, 0) TiO₂ nanotubes are first studied. The smallest adsorption energies are -1.163 eV and -1.383 eV, respectively, by examining five different adsorption sites on each type of tube. Eight and six adsorption sites were considered for OH adsorbtion on the H terminated (0, 6) and (9, 0) nanotubes. Water molecules are reformed with the smallest adsorption energy of -4.796 eV on the former and of -5.013 eV on the latter nanotube, respectively. For the adsorption of a single water molecule on TiO₂NT, the molecular state shows the strongest adsorption preference with an adsorption energy of -0.660 eV. The adsorption of multiple (two and three) water molecules on TiO₂NT is also studied. The calculated results show that the interactions between water molecules greatly affect their adsorption properties. Competition occurs between the molecular and dissociated states. The electronic structures are calculated to clarify the interaction mechanisms between water molecules and TiO₂NT. The bonding interactions between H from water and oxygen from TiO₂NT may be the reason for the dissociation of water on TiO₂NT.


How does measured olfactory function correlate with self-ratings of the sense of smell in patients with nasal polyposis?
The objectives of this study were to investigate correlations, before and after surgery, between olfactory function self-ratings and measurements, and self-ratings of nasal obstruction and smell; and to establish cutoff points of self-rating scores for smell reduction in patients with nasal polyposis (NP). Prospective study. A total of 80 patients with NP (36 women, 44 men; aged 49 ± 4 years) were enrolled. Self-ratings (0- to 10-point scale) and measurements of olfactory function with standardized Sniffin' Sticks odor threshold and identification tests were assessed 1 day before surgery, and at 6 weeks (26-78 days) and 7 months (132-318 days) after surgery. Relationships were studied with Spearman correlation coefficients. Cutoff points of self-rating scores for olfactory deficit were established using the receiver operating characteristic curve. Overall, olfactory function self-ratings and measurements correlated strongly preoperatively (r = -0.66, P < .0001) and postoperatively (r = -0.67 at 6 weeks and -0.66 at 7 months, P < .0001). This relationship was better in patients with previous surgery. The correlation was weaker before surgery (r = -0.35, P = .01) than after in hyposmic/anosmic patients (r = -0.74, P < .0001 at 6 weeks and r = -0.73, P = .0002 at 7 months) and was not found in normosmic patients. Self-ratings of nasal patency and smell were not correlated when two complaints were dissociated. Cutoff points of self-rating scores for smell reduction were nine units preoperatively and five units postoperatively. Self-ratings and measurements of olfactory function correlated well before and after surgery in NP patients with olfactory deficits. Self-ratings were not reliable pre- and postoperatively in normosmic patients.


Changes in the content of glucosinolates, polyphenols and carotenoids during lactic-acid fermentation of cruciferous vegetables: A mini review.
Cruciferous vegetables are considered functional foods because of their content of health-related compounds. They are grown and consumed in various cultures around the world. Fermentation as a preservation method for cruciferous vegetables has been used since ancient times. This process results in fermented products that have a unique flavour and odour, high bioactivity, and a distinctly different phytochemical profile than raw vegetables. In this mini review, we summarize data on changes in phytochemical content during lactic-acid fermentation of various cruciferous vegetables. The main focus was on the changes in the group of glucosinolates, polyphenols and carotenoids.


Segmental nerve conduction velocity in vibration-exposed shipyard workers.
Segmental sensory nerve conduction velocity (SNCV) was measured from the wrists to the hands and digits of a population of vibration-exposed shipyard workers. This study was designed to investigate whether SNCV was selectively slowed in the fingers and whether a laboratory approach could be adapted for robust field use. Wrist-palm, palm-proximal digit, and digital segments were determined from stimulation at the wrist with recording electrodes placed distally and adjusted to individual anatomy. The cohort was selected on the basis of current use of vibratory tools. Wrist-palm and digital segments were slower than palm-proximal digit segments for dominant and non-dominant hands and for both ulnar and median nerves. In the dominant-hand median nerve of participants with current exposure, the SNCV was 41.4 m/s (SD 8.0) for the wrist-palm segment, 50.8 (SD 9.5) for the palm segment, and 42.1 m/s (SD 9.3) for the digital segment. Temperature had an important effect on nerve conduction velocity but not equally across segments. Other explanatory variables had modest effect on SNCV. Reduced SNCV in the digits may be a consequence of industrial exposure to vibration. Each sensory nerve segment appeared to have a different characteristic velocity and different pattern of association with skin temperature. There are differences between median and ulnar nerve segments, with potentially important consequences when standard distances are used to assess wrist-digit velocity.