Low maternal alcohol consumption during pregnancy and oral clefts in offspring: the Slone Birth Defects Study.
The association between maternal alcohol consumption during pregnancy and oral clefts in offspring remains unclear. We studied this relation in a case-control surveillance study of birth defects. From 1983 to 1997, we recruited 5956 study subjects from greater Boston, Philadelphia, Toronto, and parts of Iowa. The cases were liveborn infants with cleft palate alone (CP; n = 205), cleft lip and palate (CLP; n = 383), cleft lip alone (CL; n = 259), or Pierre-Robin sequence (n = 65). The controls (n = 4272) were infants who had no oral clefts but had one or more of the following defects: malformations of the digestive tract, reproductive organs, abdominal wall, and respiratory tract; chromosomal anomalies; inguinal hernia; tumors; and Mendelian inherited disorders. Based on maternal reports of alcohol consumption during the first 4 months of pregnancy, we derived average weekly consumption, average number of drinks per drinking day, and the maximum number of drinks consumed in a given day. The mothers also provided data on potential confounding or modifying variables, such as vitamin supplement use. There was no relation between maternal alcohol consumption during pregnancy and CL or CP. The odds ratios (ORs) for cleft lip with or without palate (CL/P) were 1.0, 1.1, and 0.9 in women who consumed <1.0, 1.0-2.9, and 3.0 + drinks per week, respectively. These findings did not change when we considered possible modifying effects of vitamin supplement use. Our findings do not support an association between oral clefts and a low level of alcohol consumption.


Quantity and translation efficiency of liver microsomes in young and old rats following partial hepatectomy.
1. Liver microsomal quantity decreased in young rats 2 days after partial hepatectomy or sham operation, increased to preoperative values by 8 days, and remained unchanged 16 days following surgery. 2. In old rats, microsomal quantity remained unchanged following surgery, but increased in sham-operated controls. 3. Translational efficiency of microsomes from young, sham-operated animals was unaffected, but decreased 2 days after partial hepatectomy. 4. In old, sham-operated controls, efficiency decreased, but remained unchanged 2 days after partial hepatectomy. 5. Eight and 16 days after surgery, efficiency of microsomes from young and old animals appeared indistinguishable, and were similar to those of adults before surgery.


Vascular endothelial growth factor gene-activated matrix (VEGF165-GAM) enhances osteogenesis and angiogenesis in large segmental bone defects.
Healing of fractures is dependent on vascularization of bone, which is in turn promoted by VEGF. It was shown that 0.1 and 1 mg of pVEGF165-GAM led to a significant increase in vascularization and bone regeneration in defects that would otherwise have led to atrophic nonunions. One reason for lack of bone healing in nonunions is the absence of vascularization. In skeletogenesis, which is tightly linked to angiogenesis, vascular endothelial growth factor (VEGF) promotes the vascularization of the growth plate and transformation of cartilage to bone. We postulate that a gene-activated matrix (GAM), created with a plasmid coding for human VEGF165, coated on a collagen sponge could efficiently accelerate bone healing in large segmental defects. Sixty New Zealand white rabbits received a 15-mm critical size defect on one radius, which was filled with either 0.1 or 1 mg plasmid-DNA as GAM. Radiographs were obtained every 3 weeks. After 6 or 12 weeks, animals were killed. New bone was measured by microCT scans. Vascularity was measured using anti-CD31 staining of endothelial cells in 18 regions of interest per implant. Scaffold and control plasmid showed no defect healing, whereas most of the animals in the VEGF groups showed partial or total bone regeneration. Significantly more bone was found in the VEGF groups, with no significant differences between the 0.1- and 1-mg groups. Immunohistochemical staining of endothelial cells revealed that the VEGF groups showed two to three times the number of vessels and a significantly larger endothelial area after 6 weeks. Twelve weeks after surgery, the amount of vascularization decreased, whereas more new bone was detectable. The rabbit critical size defect was appropriate in size to produce atrophic nonunions. We showed that angiogenesis and osteogenesis can be promoted by a VEGF165-GAM that is an appropriate tool to induce bone healing in atrophic nonunions.


High Dietary ω-6:ω-3 PUFA Ratio Is Positively Associated with Excessive Adiposity and Waist Circumference.
The aim of this study was to analyze dietary ω-6:ω-3 polyunsaturated fatty acid (PUFA) ratio and its association with adiposity and serum adiponectin levels in a Mexican population. In this cross-sectional study, individuals with a BMI ≥ 18.5 kg/m2, were classified using four methods to measure adiposity. Parameters of body composition were measured by InBody 3.0. Diet intake was evaluated prospectively using a 3-day written food record. Serum high-molecular weight adiponectin isoform was measured using an ELISA assay. Biochemical and adiposity variables were analyzed by tertiles of dietary ω-6:ω-3 PUFA ratio. A total of 170 subjects were recruited with a mean age of 36.9 ± 11.8 years. The 73.5% of subjects were women. Subjects in the higher tertile of dietary ω-6:ω-3 PUFA ratio had more adiposity and higher levels of triglycerides, VLDL-c, glucose, insulin and HOMA-IR than those in the first tertile (p < 0.05). Adiponectin levels showed a trend according to dietary ω-6:ω-3 PUFA ratio (p = 0.06). A linear regression model showed that waist circumference, insulin, and HOMA-IR have positive associations with dietary ω-6:ω-3 PUFA ratio. This study suggests that high dietary ω-6:ω-3 PUFA ratio is positively associated with excessive adiposity and worse metabolic profile.


Naringenin inhibits autophagy and epithelial-mesenchymal transition of human lens epithelial cells by regulating the Smad2/3 pathway.
Cataract is the number one cause of blindness in the world. Fibrosis of the lens is the main cause of cataract. Pathological epithelial-mesenchymal transition (EMT) plays an important role in the development of fibrotic cataract. Inhibition of EMT may be an effective treatment for fibrosis of lens epithelial cells. Naringin (NRG) is one of the major citrus flavonoids, which has many pharmacological properties, including anti-inflammatory and cardioprotective. However, the effect of NRG on cataract induced by abnormal fibrosis of LECs is not clear. Herein, we found NRG inhibited transforming growth factor β2 (TGFβ2)-induced SRA01/04 cell viability. Additionally, NRG inhibited TGFβ2-induced cell migration and EMT. We further noticed that NRG inhibited autophagy and Smad2/3 phosphorylation in LECs. We therefore thought Naringenin inhibited autophagy and EMT of human LECs by regulating the Smad2/3 pathway. NRG could therefore serve as a promising drug for cataract treatment.


[Evaluation of selected immunocompetent cells expression in gastric mucosa in children with Helicobacter pylori infection before and after eradication treatment--a preliminary study].
Helicobacter pylori infection activates local immunological response and causes mononuclear cells infiltration in the gastric mucosa. On this account the studies on lymphocyte subpopulations in the gastric mucosa in children during Helicobacter pylori infections are inconsistent. It has been shown that the morphological status of gastric mucosa in children with Helicobacter pylori infection is different than in adult patients. THE AIM OF THE STUDY was the evaluation of chosen immunocompetent cells expression in gastric mucosa in children before and after eradication treatment. Forty-nine children with chronic abdominal pain was enrolled in the study. They were divided into the following groups: 22 children without infection (negative urease test and absence of Helicobacter pylori antigen assessed by immunoenzymatic and immunofluorescent methods) and 27 with Helicobacter pylori infection. Part of the children (11) from the second group had a follow-up endoscopy after eradication therapy. The tissue samples from the gastric antrum and fundus were obtained for morphological and immunohistochemistry assays by direct immunofluorescent and immunoenzymatic methods. There were negative Helicobacter pylori tests in group I. In the group of infected children superficial colonisation of pathogen dominated In analysed groups percentage of patients with superficial antigens and cytokines (CD3, CD4, CD8, CD20, IL-4, IL-6, INF-gamma) characteristic for each lymphocytes subpopulations were established. In infammatory infiltrations T lymphocytes CD4 and B lymphocytes CD20 dominated localised mainly in the lamina propria of the gastric mucosa. Expression of above lymphocytes subpopulations diminished after eradication treatment. After treatment the total eradication of Helicobacter pylori was observed in 5 children and in 6 patients the pathogen persisted. The dominant role in local response during Helicobacter pylori infection in children is played by T CD4 and B CD20 lymphocytes localised mainly in lamina propria of gastric mucosa. Degree of T cells CD4 and CD20 expression decreases after eradication treatment.


Longitudinal changes in dietary patterns during adult life.
Despite the growing interest in dietary patterns, there have been few longitudinal investigations. The objective of the present study was to extend an earlier method of dietary pattern assessment to longitudinal binary data and to assess changes in patterns over time and in relation to socio-demographic covariates. A prospective national cohort of 1265 participants completed a 5 d food diary at three time-points during their adult life (at age 36 years in 1982, 43 years in 1989 and 53 years in 1999). Factor analysis identified three dietary patterns for women (fruit, vegetables and dairy; ethnic foods and alcohol; meat, potatoes and sweet foods) and two patterns in men (ethnic foods and alcohol; mixed). Trends in dietary pattern scores were calculated using random effects models. Marked changes were found in scores for all patterns between 1989 and 1999, with only the meat, potatoes and sweet foods pattern in women recording a decline. In a multiple variable model that included the three time-points, socio-demographic variables and BMI time-dependent covariates, both non-manual social class and higher education level were also strongly associated with the consumption of more items from the ethnic foods and alcohol pattern and the mixed pattern for men (P < 0.0001) and the fruit, vegetables and dairy pattern and the ethnic foods and alcohol pattern for women (P < 0.01). In conclusion, longitudinal changes in dietary patterns and across socio-economic groups can assist with targeting public health initiatives by identifying stages during adult life when interventions to improve diet would be most beneficial to health.


Compartment analysis of ATP in malaria-infected erythrocytes.
The ATP concentration of malaria-infected erythrocytes changes substantially with parasite development. These alterations have been attributed to a decline in host cell [ATP], but have not been tested critically hitherto. A method for the compartmental analysis of ATP in malaria (Plasmodium falciparum)-infected human red blood cells has been developed using Sendai virus to permeabilize the host erythrocyte membrane. Permeabilization and release of host cytosol was complete within 6 to 8 minutes and ATP was measured by the luciferin-luciferase bioluminescence assay in the lysate and in the pellet. Equal ATP concentrations were found in host and parasite compartments at the trophozoite and schizont stages. Both were lower than those detected in uninfected cells. Other methods for compartment analysis of ATP are presented and discussed.


Early experiences with soft intraocular implants.
The author recounts his early experience with implants for the posterior chamber made of silicone. While the numbers are small the visual results appear to be satisfactory. The results, however, are marred by an as yet unacceptable rate of post-operative complications.


Mitogen-activated protein (MAP) kinases mediate PMMA-induction of osteoclasts.
Inflammatory osteolysis induced by implant-derived wear debris is associated with infiltration of various cell-types to the implant-bone interface leading to abundant secretion of pro-inflammatory cytokines and activation of proteinases that together lead to propagation of the localized inflammatory response and periprosthetic bone erosion. Tumor necrosis factor family members are considered to be direct mediators of inflammation and osteolysis. These cytokines exert their osteoclastic effects via activation of the transcription factor NF-kappaB and certain MAP kinases, including c-Jun, Erks and p38, all known to be essential for the development of osteoclasts. We have recently documented that the osteoclastogenic cytokines TNF and RANKL play a pivotal role in the development of inflammatory osteolysis. We have also found that PMMA particles stimulate osteoclastogenesis, at least in part, by induction of RANKL, TNF, and by activation of the transcription factor NF-kappaB. More importantly, our data indicate that inhibitors of the osteoclastogenic factors, TNF and RANKL abrogate particle-induced osteoclastogenesis. In the current study, we investigated if PMMA particles activate MAP kinases, and the potential role of these kinases as mediators of osteolysis. Using kinase assays, we show that in osteoclast precursors, PMMA particles markedly and rapidly activate p38 and ERK MAP kinases. This activation was specific, evident by complete blockade with specific inhibitory compounds. Similarly, we show that PMMA particles activate the JNK pathway, which is known to be involved in inflammatory and osteoclastogenic events. We also show that p38 MAP kinase regulates PMMA-activation of NF-kappaB, thus providing a possible mechanism for particle action in osteoclast precursors. Finally, we provide evidence that specific inhibitors of MAP kinases are capable of inhibiting PMMA-stimulated osteoclastogenesis. These data provide evidence that MAP kinases are potent mediators of particle-induced osteoclastogenesis.


[Сontamination of baby foods with ochratoxin A].
Mycotoxin ochratoxin A (OTA) is a widespread contaminant of raw cereal grains with nephrotoxic activity. Сereal-based baby foods (BF) are an important component of the infant diet. In Russia, the presence of OTA in grainbased BF is not allowed (<0.5 ng/kg), in the EU maximum limit of toxin in BF is 0.5 ng/kg. The Joint FAO/WHO Expert Committee on Food Additives (JECFA) set for OTA a provisional tolerable weekly intake of 100 ng/kg bw; the European Food Safety Authority (EFSA) – 120 ng/kg bw. The purpose of this study was to investigate the OTA content in BF (infant cereals and canned food) and assess the relevant risk to the health of children first year of life. The analysis of OTA was performed by immunoaffinity column clean-up and high performance liquid chromatography with fluorescence detection. The limit of detection and limit of quantification for OTA were 0.10 and 0.50 ng/kg, respectively. The content of OTA in BF was represented as maximum (Max), mean (M), median (Мe) and 90 percentile (90%) of all samples. The 554 BF samples based on corn, rice, buckwheat, millet, wheat, oats, barley, and mixtures of cereals were studied. OTA was detected in 32 samples of BF: in 30 of the 312 samples of infant cereals (Max – 4.95 ng/kg; M – 0.09 ng/kg, Me and 90% – 0 ng/kg) and in 2 of the 242 samples of canned food (0.34 and 0.37 ng/kg). 20 samples of BF were contaminated with OTA above the maximum limit (≥0.50 ng/kg). BF, exhibited the highest incidence of OTA, were buckwheat-based (13 of 41 samples, Max – 2.52 ng/kg, M – 0.36 ng/kg, Me – 0 ng/kg, 90% – 1.57 ng/kg) and mixed-grain (12 of 115 samples, Max – 4.95 ng/kg, M – 0.10 ng/kg, Me – 0 ng/kg, 90% – 0.14 ng/kg) infant cereals. OTA was also detected in 2 of 40 samples of oat-based infant cereals (0.19 and 0.60 ng/kg), in 2 of 72 samples of rice-based infant cereals (0.18 and 0.48 ng/kg) and in 1 of 37 samples of wheat-based infant cereals (0.13 ng/kg). None of the 4 samples of corn-based and of the 3 samples of millet-based infant cereals contained OTA. Calculations showed that for infants the daily ochratoxin A dietary intake did not exceed 6.8 ng/kg bw. This value of OTA intake is below the levels, proposed as tolerable intake. Thus, one can conclude that cereal-based BF (infant cereals and canned food) are moderately contaminated with OTA and there is not a significant toxicological risk to the health of children of first year of life. However, identification of BF samples containing OTA above the maximum limit, demonstrates the need for thorough monitoring of the quality of the products from the manufacturers and regulatory authorities.


Methylsulphone metabolites of m-dichlorobenzene as ligands for alpha 2u-globulin in rat kidney and urine.
1. Kidneys from rats given oral doses of either 3,5- or 2,4- dichlorophenyl[14C]methylsulphide contained the corresponding sulphones that were associated with a protein which has been isolated and characterized by SDS-polyacrylamide gel electrophoresis and immunoblot analysis to be alpha 2u-globulin. 2. The same methylsulphone-alpha 2u-globulin complex was isolated from the urine from rats doses with 3,5-dichlorophenyl[14C]methylsulphide (0.3-1.0% of dose, 8.5% of 14C in urine. 3. The stoichiometry of binding of the isolated methylsulphone-alpha 2u-globulin complex was shown to be 0.54-0.78 nmol/nmol protein. This binding was not covalent.


[Future guidelines for medical technologists].
In this symposium, ways in which medical technologists can contribute as supporting members in Japan's health care system will be discussed. Improvement in the job specifications of health care professionals has been identified as a major pillar of Japanese health care reform. As members of the medical support team, along with university professors and medical laboratory researchers, medical technologists will be expected to improve their knowledge and skill. Medical technologists should therefore be prepared to make great efforts to progress according to expectations, and these things must be kept in mind as a future guideline for medical technologists in Japan.


Control of Ice Propagation by Using Polyelectrolyte Multilayer Coatings.
Ice propagation is of great importance to the accumulation of ice/frost on solid surfaces. However, no investigation has been reported on the tuning of ice propagation through a simple coating process. Herein, we study the ice propagation behavior on polyelectrolyte multilayer (PEM) surfaces coated with the layer-by-layer (LBL) deposition approach. We discover that ice propagation is strongly dependent on the amount of water in the outermost layer of PEMs, that is, the ice propagation rate increases with the amount of water in the outermost layer. The ice propagation rate can be tuned by up to three orders of magnitude by changing the polyelectrolyte pairs, counterions of the outermost polymer layer, or the salt concentration during the preparation of PEMs. Because the simple, versatile, and inexpensive LBL deposition approach is generally applicable to almost all available surfaces, the PEM coatings can tune ice propagation on a wide range of substrates.


Apneic seizures in infants: role of continuous EEG monitoring.
Respiratory compromise is not uncommon in epileptic seizures. However, pure apneic seizures are rare. In this study, we report 10 children who presented with pure apneic seizures. All the children were admitted because of apneic events. Seizures were also considered in the differential diagnosis. Six patients had nonspecific findings consisting of multifocal interictal epileptiform activity with no event correlation. Continuous 24-72 hours electroencephalogram (EEG) was performed in all patients to rule out apneic seizures. Ictal EEG showed high correlation with the apneic episodes, confirming the diagnosis of apneic seizures. Our study suggests that continuous EEG monitoring is essential in the diagnosis and treatment of apneic seizures.


Volatile compounds in dry dog foods and their influence on sensory aromatic profile.
The aim of this study was to determine volatile compounds in dry dog foods and their possible influence on sensory aromatic profile. Grain-free dry dog foods were compared to dry dog foods manufactured with grain, but also with different protein sources for their aromatic volatiles. Solid-phase microextraction/gas chromatography/mass spectrometry was used to determine the aromatic compounds present in the headspace of these samples. Partial Least Squares regression was performed to correlate the instrumental aromatic data with the descriptive aroma analysis data. A total of 54 aromatic compounds were tentatively identified in the dry dog food samples, with aldehydes and ketones being the most represented organic volatiles group. Grain-added products were on the average higher in total volatiles than grain-free products. Partial Least Squares regression analysis indicated possible connections with sensory aromatic profile and grain-added samples, such as rancid aroma and aldehydes, especially hexanal. The results of this study showed that dry dog foods are products with complex odor characteristics and that grain-free products are less aromatic.


Room-Temperature Oxidation of Formaldehyde by Layered Manganese Oxide: Effect of Water.
Layered manganese oxide, i.e., birnessite was prepared via the reaction of potassium permanganate with ammonium oxalate. The water content in the birnessite was adjusted by drying/calcining the samples at various temperatures (30 °C, 100 °C, 200 °C, 300 °C, and 500 °C). Thermogravimetry-mass spectroscopy showed three types of water released from birnessite, which can be ascribed to physically adsorbed H2O, interlayer H2O and hydroxyl, respectively. The activity of birnessite for formaldehyde oxidation was positively associated with its water content, i.e., the higher the water content, the better activity it has. In-situ DRIFTS and step scanning XRD analysis indicate that adsorbed formaldehyde, which is promoted by bonded water via hydrogen bonding, is transformed into formate and carbonate with the consumption of hydroxyl and bonded water. Both bonded water and water in air can compensate the consumed hydroxyl groups to sustain the mineralization of formaldehyde at room temperature. In addition, water in air stimulates the desorption of carbonate via water competitive adsorption, and accordingly the birnessite recovers its activity. This investigation elucidated the role of water in oxidizing formaldehyde by layered manganese oxides at room temperature, which may be helpful for the development of more efficient materials.


Toll-Like Receptor 2 Is Required for Inflammatory Process Development during Leishmania infantum Infection.
Visceral leishmaniasis (VL) is a chronic and fatal disease caused by Leishmania infantum in Brazil. Leukocyte recruitment to infected tissue is a crucial event for the control of infections such as VL. Among inflammatory cells, neutrophils are recruited to the site of Leishmania infection, and these cells may control parasite replication through oxidative or non-oxidative mechanisms. The recruitment, activation and functions of the neutrophils are coordinated by pro-inflammatory cytokines and chemokines during recognition of the parasite by pattern recognition receptors (PRRs). Here, we demonstrated that the Toll-like receptor 2 (TLR2) signaling pathway contributes to the development of the innate immune response during L. infantum infection. The protective mechanism is related to the appropriate recruitment of neutrophils to the inflammatory site. Neutrophil migration is coordinated by DCs that produce CXCL1 and provide a prototypal Th1 and Th17 environment when activated via TLR2. Furthermore, infected TLR2-/- mice failed to induce nitric oxide synthase (iNOS) expression in neutrophils but not in macrophages. In vitro, infected TLR2-/- neutrophils presented deficient iNOS expression, nitric oxide (NO) and TNF-α production, decreased expression of CD11b and reduced L. infantum uptake capacity. The non-responsive state of neutrophils is associated with increased amounts of IL-10. Taken together, these data clarify new mechanisms by which TLR2 functions in promoting the development of the adaptive immune response and effector mechanisms of neutrophils during L. infantum infection.


Turkish Validity and Reliability Study of Challenge-Hindrance Demands Scale for the Nursing Profession.
This study aims to adapt "the Challenge-Hindrance Demands Scale for Nursing Professional" developed by Mahaverachartkul and Sooraksa; regarding "how nurses who are under heavy workload and stress as well as intense and tiring working hours perceive many stressful situations in the working environment as challenges or hindrances" to Turkish language and bring it to the use of national literature. In terms of method, the research was designed within the scope of the quantitative research model. Data collected from 450 nurses were used in this study. The research data were analyzed in SPSS 26.0 and AMOS 24.0 statistical programs. The validity of the scales used in this study was evaluated with exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). According to the EFA findings of the Challenge Demands Scale, when the KMO value (0.919) and the Bartlett sphericity test value (X2 (78) = 4121.203; p=0.001) were examined, it was seen that the data were suitable for analysis. When the CFA findings of the Challenge Demands Scale were examined, it was seen that the fit indices were at an acceptable level (X2 (60) = 223.912; p=0.001; CMIN/df = 3.732; CFI = 0.960; TLI = 0.948; RMSEA = 0.078; SRMR = 0.039). According to the EFA findings of the Hindrance Demands Scale, when the KMO value (0.947) and the Bartlett sphericity test value (X2 (78) = 5263.056; p=0.001) were examined, it was seen that the data were suitable for analysis. When the CFA findings of the Hindrance Demands Scale were examined, it was seen that the fit indices were at an acceptable level (X2 (61) = 208.794; p=0.001; CMIN/df = 3.423; CFI = 0.972; TLI = 0.964; RMSEA = 0.073; SRMR = 0.032). In conclusion, the Challenge-Hindrance Demands Scale for Nursing Professionals with 13 items and four dimensions developed to measure the stress, hindrance, and challenge levels of nurses in their professional life in Turkey may be used in future studies.


4-1BB ligand signaling to T cells limits T cell activation.
4-1BB ligand (4-1BBL) and its receptor, 4-1BB, are both induced on T cells after activation, but little is known about the role of 4-1BBL. In this study we show that 4-1BBL can transmit signals that limit T cell effector activity under tolerogenic conditions. Cross-linking 4-1BBL inhibited IL-2 production in vitro, primarily with suboptimal TCR stimulation. Furthermore, naive 4-1BBL-deficient OT-II transgenic T cells displayed a greater conversion to effector T cells in vivo when responding to soluble OVA peptide in wild-type hosts, whereas development of Foxp3(+) regulatory T cells was not altered. A greater number of effector T cells also differentiated from naive wild-type OT-II T cells when transferred into 4-1BB-deficient hosts, suggesting that APC-derived 4-1BB is likely to trigger 4-1BBL. Indeed, effector T cells that could not express 4-1BBL accumulated in larger numbers in vitro when stimulated with 4-1BB-expressing mesenteric lymph node dendritic cells. 4-1BBL was expressed on T cells when Ag presentation was limiting, and 4-1BBL was aberrantly expressed at very high levels on T cells that could not express 4-1BB. Trans-ligation, Ab capture, and endocytosis experiments additionally showed that T cell-intrinsic 4-1BB regulated internalization of membrane 4-1BBL, implying that the strong induction of 4-1BB on T cells may counteract the suppressive function of 4-1BBL by limiting its availability. These data suggest that 4-1BBL expressed on T cells can restrain effector T cell development, creating a more favorable regulatory T cell to effector cell balance under tolerogenic conditions, and this may be particularly active in mucosal barrier tissues where 4-1BB-expressing regulatory dendritic cells present Ag.


Accelerating CEST MRI in the mouse brain at 9.4 T by exploiting sparsity in the Z-spectrum domain.
Chemical exchange saturation transfer (CEST) is an MR contrast modality offering an enhanced sensitivity for the detection of dilute metabolites with exchangeable protons. Quantitative analysis requires the acquisition of a number of images (usually between 20 and 50 RF offsets) per Z-spectrum, leading to long acquisition times of the order of 5-40 min in practice. In this work, we explore the possibility of employing sparsity in the Z-spectrum domain (irradiation offset dimension) to provide an accelerated acquisition scheme without compromising the quality of reconstructed CEST spectra. Ex vivo and in vivo data were acquired on an experimental, small animal 9.4 T system. Three different reconstruction methods were tested: k-Z SPARSE, k-Z SLR and k-Z principal component analysis (PCA) using retrospective undersampling with net acceleration factors R = 2, 3, 5. The quality of the reconstructed data was compared with respect to CEST spectra and full magnetization transfer ratio (MTR) asymmetry maps. In both phantom and in vivo data, CEST spectra and the resulting MTR asymmetry maps were reconstructed without significant deterioration in data quality. For a low acceleration factor (R = 2, 3) all applied methods resulted in similar data quality, while for high acceleration factor (R = 5) only k-Z PCA and k-Z SLR could be used. Loss in spatial resolution was observed in reconstruction with k-Z PCA for all acceleration factors. An example of prospective undersampling with acceleration factor R = 3 and k-Z PCA reconstruction demonstrates improved CEST maps when compared with fully sampled data acquisition with either three times longer scan duration or threefold prolonged acquisition window per frequency offset. The acquisition time of CEST spectra can be significantly accelerated by exploiting the sparsity of the Z-domain. For prospective and retrospective analysis using k-Z PCA, an acceleration factor of up to R = 3 can be used without significant loss in data quality.


Hepatitis C virus-associated primary hepatocellular carcinoma in non-cirrhotic patients.
There is limited literature on hepatocellular carcinoma (HCC) in patients with chronic hepatitis C virus (HCV) infection in the absence of cirrhosis. To investigate the relationship between HCV and HCC in the absence of cirrhosis and to characterize patients with HCV infection presenting with HCC in the absence of cirrhosis. We identified all adult patients with histological confirmation of HCC between 1994 and 2007 (404 patients). A case-control design (four controls for each case with non-cirrhotic HCC) was chosen to compare characteristics and survival of HCV in HCC patients without (cases) and with (controls) cirrhosis. Conditional logistic regression analysis was used to identify factors independently associated with HCV in non-cirrhotic HCC. Eighty-seven patients with non-cirrhotic HCC were identified, six (7 %) had HCV infection in comparison with 107 of 317 (55.7 %) with cirrhotic HCC (P < 0.001). Compared with the HCV-associated HCC cirrhotic group, patients with HCV-associated HCC in the absence of cirrhosis were more likely to present with a single nodule (100 vs. 66.7 %), larger nodule size (>5 cm) (100 vs. 16.7 %), and macrovascular invasion (66.7 vs. 17.4 %) at time of diagnosis. Four of six patients with HCV-associated HCC in the absence of cirrhosis where alive at three years (all had resection), which was better survival than for HCC arising in cirrhotic livers of HCV-infected individuals (66.7 vs. 39.1 %). We found that HCV is responsible for a small minority of non-cirrhotic HCC cases representing an uncommon and poorly defined subgroup of HCC.


Inflammasome activation and formation of ASC specks in patients with juvenile idiopathic arthritis.
The formation of large intracellular protein aggregates of the inflammasome adaptor ASC is a hallmark of inflammasome activation and characteristic of autoinflammation. Inflammasome activated cells release the highly proinflammatory cytokine IL-1β in addition to ASC specks into the extracellular space. Autoinflammatory activity has been demonstrated in systemic JIA, however minimal data exist on the role of inflammasomes in other JIA subtypes. We therefore investigated, if pyroptotic cells are present in the circulation of oligo- and poly-articular JIA. Peripheral blood of JIA patients (n = 46) was investigated for ASC speck formation, a key step in inflammasome activation, by flow cytometry and immunofluorescence. Free ASC and proinflammatory cytokine levels were determined by ELISA and multiplex assay. Oligo-articular JIA patients showed a significantly increased proportion of ASC speck+ monocytes compared to poly-articular JIA patients. In serum free ASC alone is not sufficient to assess inflammasome activity and does not correlate with ASC speck+ monocytes. Compared to control several cytokines were significantly elevated in samples of JIA patients. JIA serum containing antinuclear antibodies, incubated with ASC specks boosts a secondary inflammation by IL-1β production in macrophages. For the first time, we detect ex vivo inflammasome activation by ASC speck formation in oligo- and poly-articular JIA patients. Most notably, inflammasome activation was significantly higher in oligo- compared to poly-articular JIA patients. This data suggests that inflammasome derived autoinflammation may have a greater influence in the previously thought autoimmune oligo-articular JIA patients.


Non-invasive aerosol delivery and transport of gold nanoparticles to the brain.
Targeted delivery of nanoscale carriers containing packaged payloads to the central nervous system has potential use in many diagnostic and therapeutic applications. Moreover, understanding of the bio-interactions of the engineered nanoparticles used for tissue-specific delivery by non-invasive delivery approaches are also of paramount interest. Here, we have examined this issue systematically in a relatively simple invertebrate model using insects. We synthesized 5 nm, positively charged gold nanoparticles (AuNPs) and targeted their delivery using the electrospray aerosol generator. Our results revealed that after the exposure of synthesized aerosol to the insect antenna, AuNPs reached the brain within an hour. Nanoparticle accumulation in the brain increased linearly with the exposure time. Notably, electrophysiological recordings from neurons in the insect brain several hours after exposure did not show any significant alterations in their spontaneous and odor-evoked spiking properties. Taken together, our findings reveal that aerosolized delivery of nanoparticles can be an effective non-invasive approach for delivering nanoparticles to the brain, and also presents an approach to monitor the short-term nano-biointeractions.


Current Opinions on New-Onset Left Bundle Branch Block after Transcatheter Aortic Valve Replacement and the Search for Physiological Pacing.
Transcatheter aortic valve replacement possesses a high validity for patients with aortic stenosis who are considered high risk for aortic valve replacement surgery, nowadays it is also considered for patients with intermediate risk or even lower risk in certain situations. The incidence of new conduction abnormalities remains to be a tough problem, in particular, left bundle branch block. New-onset left bundle branch block is a major concern despite improvements in valve technology, and it may affect postoperative prognosis. Understanding the anatomical relationship between the conduction system and the aortic root, clarify factors related to the procedure, devices, and patients, might help to reduce the conduction abnormalities. Physiological pacing has emerged as a reasonable pacing strategy for patients with cardiac insufficiency post-valve replacement, especially combined with left bundle branch block. The purpose of this review is to summarize the current opinion on the incidence of new-onset left bundle branch block associated with transcatheter aortic valve replacement, to offer insights into its anatomical and procedural causes, clinical consequences, and more importantly, the prospect of applying physiological pacing as a therapeutic method for these patients.


Reversal of dabigatran effects in models of thrombin generation and hemostasis by factor VIIa and prothrombin complex concentrate.
The oral thrombin inhibitor dabigatran has the drawbacks that it does not have a validated antidote. Data from animal studies and plasma coagulation assays suggest that prothrombin complex concentrate (PCC) or recombinant factor VIIa (FVIIa) might reverse dabigatran anticoagulation. Cellular elements make a significant contribution to hemostasis. Our goals were to (1) test the hypothesis that both FVIIa and a 4-factor PCC improve parameters of thrombin generation in the presence of dabigatran in a cell-based model; and (2) determine whether results in a cell-based model correlate with hemostasis in vivo. PCC reversed dabigatran effects on the rate, peak, and total amount of thrombin but did not shorten the lag (n = 6 experiments in triplicate). By contrast, FVIIa shortened the lag, increased the rate and peak, but did not improve total thrombin (n = 6). Effects of PCC were seen at both therapeutic and markedly supratherapeutic dabigatran levels, whereas beneficial effects of FVIIa decreased as the dabigatran level increased. The PCC effect was reproduced by adding prothrombin, factor X, and factor IX. At therapeutic dabigatran levels, both PCC and FVIIa normalized hemostasis time in a mouse saphenous vein bleeding model. A cell-based model reflects the effects on thrombin generation of clinically relevant levels of FVIIa and PCC in the presence of dabigatran. Enhancing the rate of thrombin generation and peak thrombin level appear to correlate best with hemostasis in vivo. The ineffectiveness of FVIIa at supratherapeutic dabigatran levels may explain conflicting reports of its efficacy in dabigatran reversal.


Spontaneous splenic rupture in typhoid fever.
Three cases of multidrug-resistant Salmonella typhi infection presenting as spontaneous splenic rupture are presented. One patient died and two recovered completely. This is a previously unreported presentation of typhoid fever.


Lactate stress testing in sporadic amyotrophic lateral sclerosis.
Mitochondrial dysfunction is frequently observed in ALS. Mitochondrial dysfunction may result in increased serum lactate at rest or low levels of exercise, being used for diagnostic purposes. The study investigated if resting-lactate-determination is superior to lactate-stress-testing (LST) in demonstrating mitochondrial dysfunction in ALS. Included were 15 ALS patients, 4 women, 11 men, aged 37-72. Severity of the disease was assessed by the Norris-score. The control group comprised 66 healthy subjects, 40 women, 26 men, aged 36-76. Serum lactate was determined before, three times during, and once after a constant workload with 30 W on a bicycle ergometer. According to the EIEscorial criteria 8 patients had definite, 4 probable, 3 possible ALS. Resting lactate was increased in 2 patients, 1 with definite and 1 with possible ALS. The LST was abnormal in 5 patients with definite, 1 with probable and 1 with possible ALS. The mean Norris-score was 67.8 in patients with abnormal LST and 74.6 in patients with normal LST. In conclusion, the LST is more suitable than resting-lactate-determination in demonstrating mitochondrial dysfunction in ALS. The LST suggests mitochondrial dysfunction in half of the ALS patients. Mitochondrial dysfunction in ALS is related to the clinical severity of the disease.


A MARKER-BASED METHOD FOR INFERENCES ABOUT QUANTITATIVE INHERITANCE IN NATURAL POPULATIONS.
A marker-based method for studying quantitative genetic characters in natural populations is presented and evaluated. The method involves regressing quantitative trait similarity on marker-estimated relatedness between individuals. A procedure is first given for estimating the narrow sense heritability and additive genetic correlations among traits, incorporating shared environments. Estimation of the actual variance of relatedness is required for heritability, but not for genetic correlations. The approach is then extended to include isolation by distance of environments, dominance, and shared levels of inbreeding. Investigations of statistical properties show that good estimates do not require great marker polymorphism, but rather require significant variation of actual relatedness; optimal allocation generally favors sampling many individuals at the expense of assaying fewer marker loci; when relatedness declines with physical distance, it is optimal to restrict comparisons to within a certain distance; the power to estimate shared environments and inbreeding effects is reasonable, but estimates of dominance variance may be difficult under certain patterns of relationship; and any linkage of markers to quantitative trait loci does not cause significant problems. This marker-based method makes possible studies with long-lived organisms or with organisms difficult to culture, and opens the possibility that quantitative trait expression in natural environments can be analyzed in an unmanipulative way.


Bladder cancer and smoking. Part 3: influence of perceptions and beliefs.
This is the third of a four-part series on bladder cancer and smoking. Part one examined the risks factors for bladder cancer, emphasizing that although there are many risk factors, smoking is the main predisposing factor for the disease. Part two presented an overview of bladder cancer, including diagnosis and management of the disease. Part three seeks to determine the extent to which people's concept of what constitutes good health is influenced by their perceptions and beliefs. It then looks at whether educational support, specifically health promotion and health education, are effective in increasing the individual's awareness of the dangers of smoking for their health, and consequently in changing existing behaviours or dissuading them from becoming future smokers.


Maternal Carriage of Group B Streptococcus and Escherichia coli in a District Hospital in Mozambique.
In low-income countries, data on prevalence and effects of group B Streptococcus (GBS) and Escherichia coli (E. coli) colonization among pregnant women are scarce, but necessary to formulate prevention strategies. We assessed prevalence of GBS and E. coli colonization and factors associated among pregnant women, its effect in newborns and acceptability regarding the utilized sampling methods in a semirural Mozambican hospital. Pregnant women were recruited from June 2014 to January 2015, during routine antenatal clinics at gestational age ≥ 34 weeks (n = 200); or upon delivery (n = 120). Maternal risk factors were collected. Vaginal and vagino-rectal samples for GBS and E. coli determination were obtained and characterized in terms of antimicrobial resistance and serotype. Anti-GBS antibodies were also determined. Neonatal follow-up was performed in the first 3 months after birth. Semistructured interviews were performed to investigate acceptability of sample collection methods. In total, 21.3% of women recruited were GBS carriers, while 16.3% were positive for E. coli. Prevalence of HIV was 36.6%. No association was found between being colonized by GBS and E. coli and maternal risk factors. GBS isolates were fully susceptible to penicillin and ampicillin. Serotypes V (32.4%), Ia (14.7%) and III (10.3%) were the most commonly found and 69.2% of the women tested had immunoglobuline G antibodies against GBS. E. coli isolates showed resistance to ampicillin in 28.9% and trimethoprim/sulfamethoxazole in 61.3% of the cases. Prevalence of GBS and/or E. coli colonization among pregnant women is high in this semirural community and comparable with those reported in similar settings. Four serotypes accounted for nearly 70% of all isolates of GBS. Population-based data on infant GBS infections would enable the design of prevention strategies for GBS disease in Mozambique.


Embolization of polycystic kidneys as an alternative to nephrectomy before renal transplantation: a pilot study.
In autosomal polycystic kidney disease, nephrectomy is required before transplantation if kidney volume is excessive. We evaluated the effectiveness of transcatheter arterial embolization (TAE) to obtain sufficient volume reduction for graft implantation. From March 2007 to December 2009, 25 patients with kidneys descending below the iliac crest had unilateral renal TAE associated with a postembolization syndrome protocol. Volume reduction was evaluated by CT before, 3, and 6 months after embolization. The strategy was considered a success if the temporary contraindication for renal transplantation could be withdrawn within 6 months after TAE. TAE was well tolerated and the objective was reached in 21 patients. The temporary contraindication for transplantation was withdrawn within 3 months after TAE in 9 patients and within 6 months in 12 additional patients. The mean reduction in volume was 42% at 3 months (p = 0.01) and 54% at 6 months (p = 0.001). One patient required a cyst sclerosis to reach the objective. The absence of sufficient volume reduction was due to an excessive basal renal volume, a missed accessory artery and/or renal artery revascularization. Embolization of enlarged polycystic kidneys appears to be an advantageous alternative to nephrectomy before renal transplantation.


[Trabeculectomy and nonpenetrating surgery in glaucoma].
The purpose of the study is to compare the efficiency of classical trabeculectomy and with the punch and nonpenetrating deep-sclerectomy in patients with primary open angle glaucoma. The studied groups comprise patients with uncontrolled intra-ocular pressure with medical therapy and/or laser. The results of the study emphasize the following conclusions: the decrease of intra-ocular pressure is comparable in classical trabeculectomy and with punch the decrease of intra-ocular pressure is comparable in classical trabeculectomy and nonpenetrating surgery. we consider the non penetrating surgery an interesting alternative to the classical trabeculectomy, with better control of intra-ocular pressure the complications of non penetrating surgery are reduced.


Induction of erythroid gene expression by microcell fusion.
The molecular events which underlie lineage commitment and differentiation in hematopoietic cells are still incompletely understood. Microcell fusion is a versatile technique which has been utilized in characterizing and mapping genes involved in tumor suppression, cell senescence, and certain aspects of differentiation. Microcell fusion has the potential to contribute to the understanding of hematopoietic differentiation; however, application of this technique is limited by the need to use adherent cells as microcell donors, by the need to tag candidate chromosomes with a selectable marker, and by the need for prolonged selection of fused cells prior to characterization of their phenotype. We developed a modified technique of microcell fusion using square wave electroporation, which allows higher efficiency fusion than polyethylene glycol fusion. By using cross-species fusion and species-specific PCR primers, we were able to detect new gene induction events 48 h after microcell fusion. To study erythroid gene expression, we fused microcells from human erythroid K562 cells to murine B-lymphoid SP-2 cells. We found that microcell fusion induced the nonerythroid recipient cells to express alpha-globin mRNA in a dose-dependent manner. They also expressed RNA for beta-globin, GATA-1, and NF-E2. In contrast, there was no expression of heart- or liver-specific genes. We conclude that microcells from erythroid cells contain all the information necessary to induce expression of multiple erythroid genes. Analysis of the components of the microcells responsible for this new gene induction may allow the characterization of cellular factors responsible for erythroid-specific gene expression.


Pelvic nerve input mediates descending modulation of homovisceral processing in the thoracolumbar spinal cord of the rat.
Colonic afferents project to the lumbosacral and thoracolumbar spinal cord via the pelvic and hypogastric/lumbar colonic nerves, respectively. Both spinal regions process inflammatory colonic stimuli. The role of thoracolumbar segments in processing acute colorectal pain is questionable, however, because the lumbosacral spinal cord appears sufficient to process reflex responses to acute pain. Here, we show that activity in pelvic nerve colonic afferents actively modulates thoracolumbar dorsal horn neuron processing of the same colonic stimulus through a supraspinal loop: homovisceral descending modulation. Dorsal horn neurons were recorded in the rat thoracolumbar spinal cord after acute or chronic pelvic neurectomy and cervical cold block. Acute pelvic neurectomy or lidocaine inhibition of lumbosacral dorsal roots facilitated the excitatory response of thoracolumbar dorsal horn neurons to colorectal distention (CRD) and decreased the percentage of neurons inhibited by CRD, suggesting colonic input over the pelvic nerve inhibits thoracolumbar processing of the same stimulus. Ectopic activity developed in the proximal pelvic nerve after chronic neurectomy reactivating the inhibitory circuit, inhibiting thoracolumbar neurons. Cervical cold block alleviated the inhibition in intact or chronic neurectomized rats. However, the facilitated response after acute pelvic neurectomy was inhibited by cervical cold block, exposing an underlying descending facilitation. Inhibiting pelvic nerve input after cervical cold block had minimal effect. These data demonstrate that input over the pelvic nerve modulates the response of thoracolumbar spinal neurons to CRD by a supraspinal loop and that increasing thoracolumbar processing increases visceral hyperalgesia.


Adopting integrated management of childhood illness module at local level in Bangladesh: implications for recurrent costs.
This study estimated the recurrent cost implications of adopting Integrated Management of Childhood Illness (IMCI) at the first-level healthcare facilities in Bangladesh. Data on illnesses of children who sought care either from community health workers (CHWs) or from paramedics over a four-month period were collected in a rural community. A total of 5,505 children sought care. About 75% of symptoms mentioned by mothers were directly related to illnesses that are targeted in the IMCI. Cough and fever represented 64% of all reported complaints. Referral of patients to higher facilities varied from 3% for the paramedics to 77% for the CHWs. Had the IMCI module been followed, proportion of children needing referral should have been around 8%. Significant differences were observed between IMCI-recommended drug treatment and current practice followed by the paramedics. Adoption of IMCI should save about US$ 7 million on drugs alone for the whole country. Proper implementation of IMCI will require employment of additional health workers that will cost about US$ 2.7 million. If the current level of healthcare use is assumed, introduction of IMCI in Bangladesh will save over US$ 4 million.


Outcome of Hepatectomy for Huge Hepatocellular Carcinoma.
In spite of the recent improved results of hepatectomy for huge hepatocellular carcinomas (HCC), the prognosis of patients with huge HCCs is still poor compared to that of patients with small HCCs. This study was performed to compare the results of hepatectomy between patients with huge HCCs and those with small HCCs, to identify the prognostic factors in patients with huge HCCs, and to determine the preoperative selection criteria. We retrospectively analyzed 51 patients who underwent hepatectomy, between July 1994 and February 2009 at Dankook University Hospital. Patients with HCC≥10 cm were classified in large (L) group and others were classified in small (S) group. The clinicopathological features, operative procedures, and postoperative outcome were compared between both groups and various prognostic factors were investigated in group L. Eleven patients were classified in group L. Tumor size, vascular invasion, and tumor stage were higher in group L. Postoperative morbidity was higher in group L, but mortality was not different between the groups. Disease-free survivals were significantly lower in group L than in group S (36.4%, and 24.2% vs. 72.0%, and 44.0% for 1- and 3-year), but overall survival rates were similar in both groups (45.5%, and 15.2% in group L vs. 60.3%, and 41.3% in group S for 3- and 5-year). Presence of satellite nodules was the only prognostic factor in multivariate analysis after surgery for huge HCC. Regardless of tumor size, huge HCCs deserve consideration for surgery in patients with preserved liver function. Furthermore, the effect of surgery could be maximized with appropriate selection criteria, such as huge HCC without satellite nodules.


[Evaluation of cultural service value of aquaculture pond ecosystem: a case study in a water conservation area of Shanghai].
Pond aquaculture has existed in China for thousands of years, which has not only contributed great economic value, but also presented cultural value for human beings. With the development and upgrading of Chinese economy and culture, these values will be highlighted further. To evaluate the cultural service value of pond aquaculture ecosystem would provide a scientific base to the policy-making to avoid or reduce the wrong design-making or avoid the policy-malfunction, and also, to promote the development of aquaculture and related recreational fishing industry, increase the added value of aquaculture and the income of fish-farmers, and promote the economic development of rural area. Based on the survey data from the aquaculture ponds in the water conservation area of Dianshan Lake in Qingpu District of Shanghai and the related statistical data, the cultural service value including recreational value and existence value of the aquaculture pond ecosystem in the area was estimated by means of travel cost method (TCM) and contingent valuation method (CVM). The total cultural service value of this ecosystem was about 213 million Yuan x a(-1) or 231296. 69 Yuan x hm(-2) x a(-1), being 5. 25 times of the market value of aquaculture products, among which, recreational value was about 189 million Yuan x a(-1), and existence value was about 24 million Yuan x a(-1). It was suggested that in the construction of new rural areas of Shanghai, sufficient attention should be paid on the full play of the cultural service value of aquaculture pond ecosystem.


Compartmentalization of drug resistance-associated mutations in a treatment-naive HIV-infected female.
Development of a drug-resistant variant of HIV-1 has been one of the major concerns contributing to the transmission of the virus. A 40-year-old woman presented to the clinic with micosis and oral candidiasis. The subject was referred for HIV-1 diagnosis. Subsequent investigations revealed a very low CD4 T cell count (48 cell/microl blood) and high plasma HIV-1 RNA load (4.33 x 10(5) copy/ml). A 1.3-kb pol fragment was sequenced in virus collected from plasma and the vaginal compartment. Plasma virus had no mutation in reverse transcriptase and one mutation in protease (L63P). On the other hand vaginal virus contained L63P and M184V mutations in protease and reverse transcriptase, respectively. These mutations were accompanied by several other mutations in previously identified CTL epitopic regions of the two genes. In the absence of antiretroviral treatment, a drug-resistant mutant was thought to develop because of immune pressure. This is the first report describing the role of immune pressure in the development of a drug-resistant virus.


Participation: the key to learning for patients in antepartal clinics.
An approach to patient education which recognized successful participation in the learning process as a key factor in providing information for antepartal clinic patients, known to be poorly motivated, was instituted without changing any system or organization and using a minimal amount of nursing and patient time. Important information on care during pregnancy, labor and delivery, and care of the newborn was shared. Group process also provided a vehicle for expression of feelings, opportunity for reassurance, and direction for particular action. The difficulties inherent in this approach to learning are recognized and recommendations are made for dealing with them.


Homologous desensitization of rat heart cells to beta-adrenergic stimulation and the absence of alpha-adrenergic or prostaglandin E1 effects.
Epinephrine is shown to stimulate heart cell beating by both alpha- and beta-adrenergic mechanisms. The beta-adrenergic effect undergoes desensitization in one to two minutes after beta-agonist addition. A beta-antagonist did not cause desensitization. The desensitization response is quantitatively related to the concentration of cAMP produced in the cells. The alpha-adrenergic component of epinephrine action does not undergo desensitization nor does it have effects on the beta-adrenergic stimulation of cell beating or cAMP production. Other alpha-agonists and antagonists also have no effect on cAMP production. Prostaglandin E1 increased cellular cAMP by a mechanism that was additive with the beta-adrenergic mechanism. Both prostaglandin E1 and beta-agonists caused phosphorylation of both glycogen phosphorylase and glycogen synthase. Prostaglandin E1 did not desensitize the cells to beta-adrenergic stimulation of cAMP. The data show that heart cells undergo a rapid homologous desensitization to beta-agonists when treated with epinephrine or isoproterenol. The desensitization is quantitatively related to the cellular cAMP concentration, but cAMP produced by another mechanism does not desensitize the cells. No alpha-adrenergic effects on the beta-induced desensitization were observed.


Online Experiences, Internet-Fostered Connection, Resilience, and Adjustment Among Adolescent Siblings of Children With Cancer.
Pediatric cancer disrupts the lives of siblings in many ways, including physical separations from family and friends that increase risk for distress. Research suggests that siblings use technology and social media to connect with friends and family and seek social support and interaction. However, this may expose siblings to negative online experiences that can erode self-esteem, reducing resilience. This study explored the relationship between online experiences, internet-fostered connection, resilience, and psychosocial health among siblings of children with cancer. Participants included adolescent siblings (N = 81; aged 12-17 years) of children with cancer. Most were female (56.8%), and 50.6% represented racially or ethnically minoritized groups. Online experiences, social media use, resilience, and psychosocial health were self-reported and analyzed using structural equation modeling. A majority of siblings reported moderate to severe posttraumatic stress symptoms (PTSSs) (59%) and elevated emotional and behavioral difficulties (EBDs) (53%). Experiencing more positive online experiences was associated with greater perceived connection to family and friends online, but not resilience, PTSSs, or EBDs. In contrast, higher negative online experience scores were significantly associated with more PTSSs and EBDs. In addition, the association between negative online experiences and EBDs was significantly mediated by a negative association between negative online experiences and resilience. Although social media may be a valuable tool for helping siblings of children with cancer garner social support, negative online experiences may be detrimental to their adjustment. Efforts should be made to preserve and foster resilience among siblings who use social media for support.


Syndecan-1 Acts as an Important Regulator of CXCL1 Expression and Cellular Interaction of Human Endometrial Stromal and Trophoblast Cells.
Successful implantation of the embryo into the human receptive endometrium is substantial for the establishment of a healthy pregnancy. This study focusses on the role of Syndecan-1 at the embryo-maternal interface, the multitasking coreceptor influencing ligand concentration, release and receptor presentation, and cellular morphology. CXC motif ligand 1, being involved in chemotaxis and angiogenesis during implantation, is of special interest as a ligand of Syndecan-1. Human endometrial stromal cells with and without Syndecan-1 knock-down were decidualized and treated with specific inhibitors to evaluate signaling pathways regulating CXC ligand 1 expression. Western blot analyses of MAPK and Wnt members were performed, followed by analysis of spheroid interactions between human endometrial cells and extravillous trophoblast cells. By mimicking embryo contact using IL-1β, we showed less ERK and c-Jun activation by depletion of Syndecan-1 and less Frizzled 4 production as part of the canonical Wnt pathway. Additionally, more beta-catenin was phosphorylated and therefore degraded after depletion of Syndecan-1. Secretion of CXC motif ligand 1 depends on MEK-1 with respect to Syndecan-1. Regarding the interaction of endometrial and trophoblast cells, the spheroid center-to-center distances were smaller after depletion of Syndecan-1. Therefore, Syndecan-1 seems to affect signaling processes relevant to signaling and intercellular interaction at the trophoblast-decidual interface.


Molecular mass and antitumor activities of sulfated derivatives of alpha-glucan from Poria cocos mycelia.
Two kinds of water-insoluble (1-->3)-alpha-D-glucan samples, ab-PCM3-I and ac-PCM3-I, isolated from different Poria cocos mycelia were sulfated, to produce two series of water-soluble derivatives ab-PCM3-I-S1-S5 and ac-PCM3-I-S1-S5, respectively. The derivatives having different weight-average molecular mass (Mw) were produced by changing reaction temperature and time as well as molar ratios between chlorosulfonic acid and number of hydroxyl groups in the glucan. The degrees of substitution (DS) of the sulfated derivatives were analyzed by elemental analysis (EA) to be 0.39-0.67 for ab-PCM3-I-S and 0.73-0.96 for ac-PCM3-I-S, respectively. The Mw and the intrinsic viscosity ([eta]) of the samples ab-PCM3-I-S and the ac-PCM3-I-S were measured by size exclusion chromatography combined with laser light scattering (SEC-LLS) and viscometry in phosphate buffer solution (PBS) at 37 degrees C. The results indicated that their Mw ranged from 2.0 to 11.3 x 10(4) for the samples ab-PCM3-I-S, and 4.7 to 40.0 x 10(4) for the samples ac-PCM3-I-S. Moreover, the antitumor activities of the sulfated derivatives ab-PCM3-I-S and ac-PCM3-I-S against Sarcoma 180 tumor cell tested both in vitro and in vivo are significantly higher than those of the native alpha-D-glucans. Therefore, a moderate range of molecular mass from 2.0 x 10(4) to 40.0 x 10(4), relatively high chain stiffness and good water solubility of the sulfated derivatives are beneficial to the enhancement of their antitumor activities.


Cancer stem cell-like side population cells in clear cell renal cell carcinoma cell line 769P.
Although cancers are widely considered to be maintained by stem cells, the existence of stem cells in renal cell carcinoma (RCC) has seldom been reported, in part due to the lack of unique surface markers. We here identified cancer stem cell-like cells with side population (SP) phenotype in five human RCC cell lines. Flow cytometry analysis revealed that 769P, a human clear cell RCC cell line, contained the largest amount of SP cells as compared with other four cell lines. These 769P SP cells possessed characteristics of proliferation, self-renewal, and differentiation, as well as strong resistance to chemotherapy and radiotherapy that were possibly related to the ABCB1 transporter. In vivo experiments with serial tumor transplantation in mice also showed that 769P SP cells formed tumors in NOD/SCID mice. Taken together, these results indicate that 769P SP cells have the properties of cancer stem cells, which may play important roles in tumorigenesis and therapy-resistance of RCC.


Asymmetric Free-Space Light Transport at Nonlinear Metasurfaces.
Asymmetric light transport has significantly contributed to fundamental science and revolutionized advanced technology in various aspects such as unidirectional photonic devices, optical diodes, and isolators. While metasurfaces mold wave fronts at will with an ultrathin flat optical element, asymmetric transport of light cannot be fundamentally achieved by any linear system including linear metasurfaces. We report asymmetric transport of free-space light at nonlinear metasurfaces upon transmission and reflection. Moreover, we theoretically derive the nonlinear generalized Snell's laws that were experimentally confirmed by the anomalous nonlinear refraction and reflection. The asymmetric transport at optically thin nonlinear interfaces is revealed by the concept of a reversed propagation path. Such an asymmetric transport at metasurfaces opens a new paradigm for free-space ultrathin lightweight optical devices with one-way operation including unrivaled optical valves and diodes.


Development of food lists as a first step to develop a food frequency questionnaire for toddlers in a multi-ethnic population.
Toddlerhood is an important stage of growth, thus understanding the food intake of children in this age group is important. In Singapore, there is currently no simple tool, such as Food Frequency Questionnaire (FFQ), to collect dietary information from this ethnically diverse age group. Generating an appropriate food list is a crucial step in the development of a FFQ and this step is not clearly documented in the literature. The purpose of this study is to generate food lists and portion sizes for toddlers from three major ethnic groups in Singapore and document the processes involved in this first stage. A total of 30 mothers (equal number of Malays, Indians and Chinese) of 11-24-month-old children completed three-day food records and participated in the focus group discussion. The reported food items were then categorised into food groups. The food lists varied by ethnic groups with the longest list obtained from Chinese toddlers. There were also other foods that were then classified as common foods for all ethnicities. Commonly used utensils among the three ethnic groups were small-sized bowls, plates, cups and spoons. For portion sizes, these utensils were typically half-filled for the toddlers. As all Singaporeans have access to the same foods, the ethnic-specific food lists generated in this study could be combined into one list. Together with portion sizes, this information can be used for developing a semi-quantitative FFQ.


The use of advanced web-based survey design in Delphi research.
A discussion of the application of metadata, paradata and embedded data in web-based survey research, using two completed Delphi surveys as examples. Metadata, paradata and embedded data use in web-based Delphi surveys has not been described in the literature. The rapid evolution and widespread use of online survey methods imply that paper-based Delphi methods will likely become obsolete. Commercially available web-based survey tools offer a convenient and affordable means of conducting Delphi research. Researchers and ethics committees may be unaware of the benefits and risks of using metadata in web-based surveys. Discussion paper. Two web-based, three-round Delphi surveys were conducted sequentially between August 2014 - January 2015 and April - May 2016. Their aims were to validate the Australian nurse practitioner metaspecialties and their respective clinical practice standards. Our discussion paper is supported by researcher experience and data obtained from conducting both web-based Delphi surveys. Researchers and ethics committees should consider the benefits and risks of metadata use in web-based survey methods. Web-based Delphi research using paradata and embedded data may introduce efficiencies that improve individual participant survey experiences and reduce attrition across iterations. Use of embedded data allows the efficient conduct of multiple simultaneous Delphi surveys across a shorter timeframe than traditional survey methods. The use of metadata, paradata and embedded data appears to improve response rates, identify bias and give possible explanation for apparent outlier responses, providing an efficient method of conducting web-based Delphi surveys.


The use of stereotactic excisional biopsy in the management of invasive breast cancer.
Stereotactic breast biopsy techniques minimize the surgical trauma associated with conventional wire-guided open breast biopsy for non-palpable breast lesions (NPBLs). Advanced breast biopsy instrumentation (ABBI) allows for a 2-cm core of breast tissue to be excised under stereotactic guidance in an outpatient setting. We report our initial experience with ABBI. Hospital charts from 89 ABBI procedures between 10/1996 and 07/2002 were retrospectively reviewed for patient characteristics, ABBI parameters, radiographic appearance, pathology, complications, and clinical follow-up. Data are presented as percentage/median (range). Median age was 59 years (range: 39-80 years), mammographic lesions were classified as calcifications 49% (44/89), soft tissue 39% (35/89), or mixed 11% (10/89). Median radiographic size was 7 mm (1-60 mm). Final pathology revealed ductal carcinoma in situ (DCIS) in 7% (6/89) and invasive cancer in 22% (20/89). Microscopically clear margins were obtained in 55% (11/20) of patients with invasive cancer. Of these, 82% (9/11) chose not to undergo further local surgical therapy. Eight patients remain disease free at 56 months (range: 41-95 months) follow-up. The ninth patient was deceased at 6 months from an unrelated cause. The overall complication rate was 3% (3/89). A definitive diagnosis was obtained in 100% of malignant and 87% of benign cases. Median waiting time was 19 days (range: 0-90 days). Our experience demonstrates that ABBI is an effective diagnostic tool for NPBLs. It is associated with minimal complications, and provides negative margins in over half of malignant cases. In selected patients with invasive cancer and negative margins, ABBI may obviate the need for further local surgical treatment. ABBI merits additional investigation as a therapeutic modality for early breast cancer.


Characterization of the interactions between Escherichia coli receptors, LPS and OmpC, and bacteriophage T4 long tail fibers.
Bacteriophages have strict host specificity and the step of adsorption is one of key factors for determining host specificity. Here, we systematically examined the interaction between the Escherichia coli receptors lipopolysaccharide (LPS) and outer membrane protein C (OmpC), and the long tail fibers of bacteriophage T4. Using a variety of LPS mutants, we demonstrated that T4 has no specificity for the sugar sequence of the outer core (one of three LPS regions) in the presence of OmpC but, in the absence of OmpC, can adsorb to a specific LPS which has only one or two glucose residues without a branch. These results strengthen the idea that T4 adsorbs to E. coli via two distinct modes, OmpC-dependent and OmpC-independent, suggested by previous reports (Prehm et al. 1976; Yu and Mizushima 1982). Isolation and characterization of the T4 mutants Nik (No infection to K-12 strain), Nib (No infection to B strain), and Arl (altered recognition of LPS) identified amino acids of the long tail fiber that play important roles in the interaction with OmpC or LPS, suggesting that the top surface of the distal tip head domain of T4 long tail fibers interacts with LPS and its lateral surface interacts with OmpC.


Insights From the National Diabetes Education Program National Diabetes Survey: Opportunities for Diabetes Self-Management Education and Support.
IN BRIEF Diabetes self-management education and support (DSMES) provides the foundation to help people with diabetes (PWD) navigate the numerous self-management decisions and complex care activities they face daily and has been shown to improve outcomes. Without DSMES, PWD often lack the skills and knowledge necessary to handle the demands of managing this chronic disease. Understanding self-management behaviors and responses to DSMES is essential for improving DSMES processes and diabetes outcomes. This article provides the most recent findings from questions regarding self-management behaviors and DSMES practices obtained through the National Diabetes Education Program National Diabetes Survey. Insights and gaps in self-management behaviors and DSMES delivery are examined to identify challenges and offer opportunities for improvement.


Random sources generating ring-shaped beams.
Two classes of scalar, stochastic sources are introduced, each capable of producing far fields with intensities forming rings. Although the Bessel-Gaussian and the Laguerre-Gaussian Schell-model sources are described by two different math models, the behavior of their degrees of coherence and, hence, the shapes of their far fields are qualitatively similar. The new beams are of importance for optical methods of particle manipulation.


Identification of a New Pathogenicity Island Within the Large pAH187_270 Plasmid Involved in Bacillus cereus Virulence.
Bacillus cereus is responsible for food poisoning and rare but severe clinical infections. The pathogenicity of B. cereus strains varies from harmless to lethal strains. The objective of this study was to characterize three B. cereus isolates isolated from the same patient and identify their virulence potentials. Three isolates of B. cereus were isolated from various blood samples from a patient who developed sepsis following a central venous catheter infection. The three isolates were compared by WGS, genotyping and SNP analysis. Furthermore, the isolates were compared by phenotypical analysis including bacterial growth, morphology, germination efficacy, toxin production, antibiotic susceptibility and virulence in an insect model of infection. According to WGS and genotyping, the 3 isolates were shown to be identical strains. However, the last recovered strain had lost the mega pAH187_270 plasmid. This last strain showed different phenotypes compared to the first isolated strain, such as germination delay, different antibiotic susceptibility and a decreased virulence capacity towards insects. A 50- kbp region of pAH187_270 plasmid was involved in the virulence potential and could thus be defined as a new pathogenicity island of B. cereus. These new findings help in the understanding of B. cereus pathogenic potential and complexity and provide further hints into the role of large plasmids in the virulence of B. cereus strains. This may provide tools for a better assessment of the risks associated with B. cereus hospital contamination to improve hygiene procedure and patient health.


Double-Stranded Structure of the Polyinosinic-Polycytidylic Acid Molecule to Elicit TLR3 Signaling and Adjuvant Activity in Murine Intranasal A(H1N1)pdm09 Influenza Vaccination.
Polyinosinic-polycytidylic acid (PIC) is a potent double-stranded RNA (dsRNA) adjuvant useful in intranasal influenza vaccination. In mice, the intensity and duration of immune responses to PIC correlated with the double-stranded chain length. A rational method to avoid PIC chain extension in PIC production is to use multiple short poly(I) molecules and one long poly(C) molecule for PIC assembly. In this study, we elucidate that a newly developed uPIC100-400 molecule comprising multiple 0.1 kb poly(I) molecules and one 0.4 kb poly(C) molecule effectively enhanced the immune responses in mice, by preventing the challenged viral propagation and inducing hemagglutinin-specific IgA, after intranasal A(H1N1)pdm09 influenza vaccination. Reduced intraperitoneal toxicity of PIC prepared with multiple short poly(I) molecules in mice indicates the widened effective range of uPIC100-400 as an adjuvant. In contrast to uPIC100-400, the PIC molecule comprising multiple 0.05 kb poly(I) molecules failed to elicit mouse mucosal immunity. These results were consistent with TLR3 response but not retinoic acid inducible gene I (RIG-I)-like receptor response in the cell assays, which suggests that the adjuvant effect of PIC in mouse intranasal immunization depends on TLR3 signaling. In conclusion, the double-stranded PIC with reduced toxicity developed in this study would contribute to the development of PIC-adjuvanted vaccines.


Pilonidal disease--a surgical enigma.
A retrospective review of 72 patients with pilonidal disease was conducted in order to examine current methods of treatment and establish certain guiding principles for success. The criteria for diagnosis included a pit of variable depth lined by epithelium or granulation tissue containing hair or from which hair had been extracted. A study of these patients suggested the possibility of a dual etiology for pilonidal disease, either congenital or acquired, acting singly or in combination. Management will be influenced by the surgeon's concept of origin in each case. These 72 patients who underwent a total of 116 operations were divided into two groups: (1) unifected sinuses and cysts, (2) infected and recurring cysts. The results of various operative procedures in both these groups indicate a higher probability of success when wide excision and open healing is employed.


[Occupational cancers in urology].
Cancers can be triggered by occupational causes. In the field of urology, bladder cancer is by far the most frequent occupationally induced tumor disease. Causes are particularly carcinogenic aromatic amines and carcinogenic polycyclic aromatic hydrocarbons. The frequency of this disease has shifted over the last decades from the classical hazard in the chemical industry to the users. Among a variety of hazardous occupations, hairdressers and painters are the best known. Rarely, renal cell carcinoma can be triggered by high trichloroethylene exposure and mesothelioma of the tunica vaginalis testis by asbestos. If a disease that can be caused by occupational activities has been confirmed (e.g. urinary bladder cancer), the risk factors must be recorded by a complete occupational history from the first employment on in order to be able to report a suspected occupational disease. In addition, spinal cord injury due to occupational and commuting accidents can lead to urinary bladder cancer over the long term.


[Studies of fibromuscular hyperplasia of vascular anastomosis].
The aim of this study was to present a retrospective analysis of occurrence, diagnosis, methods and treatment results in patients treated because of thrombosis of vascular anastomosis. Authors have tried to make and experimental model of hyperplasia of vascular anastomosis and verify a possibility of stop hyperplasia application by an optimal dose of dexamethasone. They also have evaluated an efficacy of Doppler color ultrasonography to make an early diagnosis of stenosis of vascular anastomosis.


Transgenic expression of protein phosphatase 2A regulatory subunit B56gamma disrupts distal lung differentiation.
The distal epithelium of the developing lung exhibits high-level expression of protein phosphatase 2A (PP2A), a vital signaling enzyme. Here we report the discovery that in the lung, the PP2A regulatory subunit B56gamma is expressed in a discrete developmental period, with the highest protein levels at embryonic day (e) 17, but no detectable protein in the newborn or adult. By in situ hybridization, B56gamma was highly expressed in the distal epithelium of newly forming airways and in mesenchymal cells. In contrast, expression of B56gamma was quite low in the bronchial epithelium and vascular smooth muscle. Transgenic expression of B56gamma using the lung-specific promoter for surfactant protein C (SP-C) resulted in neonatal death. Examination of lungs from SP-C-B56gamma transgenic e18 fetuses revealed proximal airways and normal blood vessels, but the tissue was densely populated with epithelial-type cells and was devoid of normal peripheral lung structure. A component of the Wnt signaling pathway, beta-catenin, was developmentally regulated in the normal lung and was absent in lung tissue from B-56gamma transgenic fetuses. We propose that B56gamma is expressed at a particular stage of lung development to modulate PP2A action on the Wnt/beta-catenin signaling pathway during lung airway morphogenesis.


Knowledge of hypertensive disorders of pregnancy among pregnant women attending antenatal clinic at a tertiary hospital in Ghana.
Hypertensive disorders of pregnancy contribute significantly to maternal and neonatal morbidity and mortality globally. Health-seeking behaviour is influenced by adequate knowledge of the condition. However, current data on pregnant women's knowledge of the condition and health-seeking behaviour are relatively scant in Ghana and has not been previously studied in the Central Region where hypertensive disorders of pregnancy was the leading cause of maternal mortality from 2016 to 2018. The study sought to generate data to fill this knowledge gap. A cross-sectional study was conducted among 404 pregnant women attending antenatal clinic at the Cape Coast Teaching Hospital from 1 April to 30 September 2020. Data on sociodemographic characteristics, including age, level of education and parity, and knowledge of hypertensive disorders of pregnancy, including its risk factors, clinical presentations and complications, were collected using structured questionnaires. The outcome variable, knowledge of hypertensive disorders of pregnancy, was a composite variable categorized as adequate and inadequate knowledge. Descriptive statistics were generated and association between independent and outcome variables were explored using chi-square and Fisher's exact tests and logistic regression methods. Sixty-two participants (15.4%) showed adequate knowledge of hypertensive disorders of pregnancy. About 62% (251/404) of respondents had heard about hypertensive disorders of pregnancy. Of those who had heard of hypertensive disorders of pregnancy, 29.4% (72/245) correctly indicated the condition was underlined by hypertension in pregnancy ⩾ 20 weeks gestation. Women with tertiary education were six times more likely to have adequate hypertensive disorders of pregnancy knowledge than those with basic education. Women with parity 1-4 were 52% less likely to have adequate knowledge compared to nulliparous women. The remarkably low proportion of pregnant women with adequate knowledge of hypertensive disorders of pregnancy in the study is worrisome because of its potential adverse implication for the health of mothers and their babies. Re-packaging the antenatal health education programme and its delivery is needed for greater impact as far as hypertensive disorders of pregnancy morbidity/mortality is concerned.


8-Ketodeoxycoformycin and 8-ketocoformycin as intermediates in the biosynthesis of 2'-deoxycoformycin and coformycin.
An enzyme has been isolated from cell-free extracts of Streptomyces antibioticus that can catalyze the reduction of 8-ketodeoxycoformycin (8-KetodCF) and 8-ketocoformycin (8-ketoCoF) to the naturally occurring nucleoside analogues 2'-deoxycoformycin (dCF) and coformycin (CoF), respectively. The partially purified reductase requires NADPH as the cofactor and stereospecifically reduces the 8-keto group of both ketonucleoside substrates to a hydroxyl group with the R configuration at C-8. This is the same configuration of the hydroxyl group as that of the dCF and CoF isolated from S. antibioticus. The reduction proceeds at the nucleoside level, and ATP is not required. The reductase is stereospecific for the NADPH cofactor in that it transfers the pro-S but not the pro-R hydrogen from C-4 of NADPH to the 8-keto group. The apparent Km for 8-ketodCF and 8-ketoCoF were 250 and 150 microM, respectively. These in vitro results, which show that 8-ketodCF and 8-ketoCoF may be intermediates in the biosynthesis of dCF and CoF, support and extend our earlier results from in vivo studies which established that adenosine and C-1 of D-ribose are the carbon-nitrogen precursors of dCF. A possible mechanism for the formation of dCF is presented.


Occlusal traits and perception of orthodontic need in eighth grade students.
In 1994, 1155 eight-grade students in Alachua County, Fla., were asked about self-perception of and level of concern for their occlusal status. Clinical assessments of orthodontic parameters were also recorded. Twenty-five percent of the students had a history of orthodontic treatment. Of the remaining students who had no history of orthodontic treatment, 74% reported satisfaction with the way their teeth looked, 64% expressed no perceived need for braces, and 57% were judged clinically to have optional or no orthodontic needs. Sex, soft tissue profile, overjet, anterior crowding, and molar classification were significantly associated with the perception of need for braces while race and overbite were not. Clinical judgment of orthodontic need differed significantly among levels of satisfaction with teeth. Eighth graders with no history of orthodontic treatment were generally satisfied with the appearance of their teeth and perceived less need for braces than clinicians.


Optogenetic and chemogenetic strategies for sustained inhibition of pain.
Spatially targeted, genetically-specific strategies for sustained inhibition of nociceptors may help transform pain science and clinical management. Previous optogenetic strategies to inhibit pain have required constant illumination, and chemogenetic approaches in the periphery have not been shown to inhibit pain. Here, we show that the step-function inhibitory channelrhodopsin, SwiChR, can be used to persistently inhibit pain for long periods of time through infrequent transdermally delivered light pulses, reducing required light exposure by >98% and resolving a long-standing limitation in optogenetic inhibition. We demonstrate that the viral expression of the hM4D receptor in small-diameter primary afferent nociceptor enables chemogenetic inhibition of mechanical and thermal nociception thresholds. Finally, we develop optoPAIN, an optogenetic platform to non-invasively assess changes in pain sensitivity, and use this technique to examine pharmacological and chemogenetic inhibition of pain.


The non-invasive evaluation technique of patellofemoral joint stress: a systematic literature review.
Introduction: Patellofemoral joint stress (PFJS) is an important parameter for understanding the mechanism of patellofemoral joint pain, preventing patellofemoral joint injury, and evaluating the therapeutic efficacy of PFP rehabilitation programs. The purpose of this systematic review was to identify and categorize the non-invasive technique to evaluate the PFJS. Methods: Literature searches were conducted from January 2000 to October 2022 in electronic databases, namely, PubMed, Web of Science, and EBSCO (Medline, SPORTDiscus). This review includes studies that evaluated the patellofemoral joint reaction force (PJRF) or PFJS, with participants including both healthy individuals and those with patellofemoral joint pain, as well as cadavers with no organic changes. The study design includes cross-sectional studies, case-control studies, and randomized controlled trials. The JBI quality appraisal criteria tool was used to assess the risk of bias in the included studies. Results: In total, 5016 articles were identified in the database research and the citation network, and 69 studies were included in the review. Discussion: Researchers are still working to improve the accuracy of evaluation for PFJS by using a personalized model and optimizing quadriceps muscle strength calculations. In theory, the evaluation method of combining advanced computational and biplane fluoroscopy techniques has high accuracy in evaluating PFJS. The method should be further developed to establish the "gold standard" for PFJS evaluation. In practical applications, selecting appropriate methods and approaches based on theoretical considerations and ecological validity is essential.


The biochemical and histological analysis of subcutaneous calcitonin and intramedullary methylprednisolone on bone repair after bone marrow ablation: an experimental comparative study in rats.
Although, glucocorticoid (GC) and calcitonin-induced changes in bone repair have been studied previously, the exact effects of these on fracture healing remain controversial. Hence, the purpose of this experimental study is to determine biochemical and histological effects of locally administrated GC and systemically administrated calcitonin on the kinetics of healing response after bone marrow ablation in rats. After having undergone marrow ablation, a steroid-treated group of rats (n = 24) received a single dose of intramedullary methylprednisolone (2 mg/kg), a calcitonin-treated group (n = 24) received intermittently administrated subcutaneous salmon calcitonin (16 IU/kg), and a control group (n = 24) received intramedullary saline (25 μl). Blood samples taken on days 1, 3, 7, 9, and 15 after ablation showed an increase in serum calcium, alkaline phosphatase (ALP), and phosphate levels in the Calcitonin and Control groups. Levels of calcium and ALP peaked on day 7 after ablation. However, an increase in phosphate levels indicated a biphasic reaction that peaked on the third and ninth day after ablation. Hypercalcemia was not observed in Steroid group because of the inhibition of osteoclastic bone resorption. In that group, the serum levels of ALP and phosphate were lower than baseline levels. The levels of urinary calcium excretion peaked 3 to 7 days after marrow ablation in the control group and 7 to 9 days after that procedure in the steroid group. Histologic evaluation showed that the rats in the control group demonstrated the expected healing period according to the histological grades and that a delay in healing occurred in the calcitonin group after day 9 because of the inhibition of osteoclastic bone resorption. All rats in the steroid group exhibited a decrease and delayed healing response. Total serum calcium, phosphate, and ALP levels increased after bilateral tibial bone marrow ablation and urine calcium and hydroxyproline excretion also increased as a factor of bone resorption. Subcutaneously administrated salmon calcitonin did not affect biochemical changes after marrow ablation. Single-dose intramedullary methylprednisolone inhibited extra-tibial bone resorption induced by cytokines after bone marrow ablation.


The xeroderma pigmentosum group C gene polymorphisms and genetic susceptibility of nasopharyngeal carcinoma.
Nasopharyngeal cancer (NPC) is a multi-factorial disease, and the genetic background may be a crucial etiologic factor. The xeroderma pigmentosum complementation group C (XPC) is mainly involved in DNA damage repair, and the sequence variants in XPC gene may modulate DNA repair capacity and consequently lead to an individual's susceptibility to NPC. The aims of this study were to examine the association between XPC Val499Ala, Lys939Gln, PAT polymorphisms and the genetic susceptibility of nasopharyngeal carcinoma (NPC) in Chinese population. We analyzed the three XPC gene polymorphisms in 153 patients with NPC and 168 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) procedure. There were significant differences in the genotype and allele distribution of XPC Val499Ala among cases and controls. The 499Val allele carriers were associated with a significantly increased risk of NPC compared with the non-carriers (OR=1.603; 95%CI,1.160 approximately 2.216, p=0.005). Consistent with the results of the genotype analysis, the 499Val/939Lys/PAT haplotype was associated with a significantly increased risk of NPC as compared with the 499Ala/939Lys/PAT haplotype (OR=1.901;95% CI, 1.284 approximately 2.814, p=0.002). The interaction between the Val499Ala polymorphism and gender or smoking status did not been found in NPC risk. Our data demonstrated that XPC 499Val allele and its haplotype were strongly associated with NPC, which indicated that Val499Ala polymorphism may be a contributing factor in the NPC development.


Transcriptome Analysis of the Melon-Fusarium oxysporum f. sp. melonis Race 1.2 Pathosystem in Susceptible and Resistant Plants.
Fusarium oxysporum f. sp. melonis Snyd. & Hans race 1.2 (FOM1.2) is the most virulent and yield-limiting pathogen of melon (Cucumis melo L.) worldwide. Current information suggest that the resistance to race 1.2 is controlled by multiple recessive genes and strongly affected by the environment. RNA-Seq analysis was used to identify candidate resistance genes and to dissect the early molecular processes deployed during melon-FOM1.2 interaction in the resistant doubled haploid line NAD and in the susceptible genotype Charentais-T (CHT) at 24 and 48 h post-inoculation (hpi). The transcriptome analysis of the NAD-FOM1.2 interaction identified 2,461 and 821 differentially expressed genes (DEGs) at 24 hpi and at 48 hpi, respectively, while in susceptible combination CHT-FOM1.2, 882 and 2,237 DEGs were recovered at 24 hpi and at 48 hpi, respectively. The overall expression profile suggests a prompt activation of the defense responses in NAD due to its basal defense-related machinery that allows an early pathogen recognition. Gene Ontology (GO) enrichment analyses revealed a total of 57 GO terms shared by both genotypes and consistent with response to fungal infection. GO classes named "chitinase activity," "cellulase activity," "defense response, incompatible interaction," "auxin polar transport" emerged as major factors of resistance to FOM1.2. The data indicated that NAD reacts to FOM1.2 with a fine regulation of Ca2+-mediated signaling pathways, cell wall reorganization, and hormone crosstalk (jasmonate and ethylene, auxin and abscissic acid). Several unannotated transcripts were recovered providing a basis for a further exploration of the melon resistance genes. DEGs belonging to the FOM1.2 genome were also detected in planta as a resource for the identification of potential pathogenicity factors. This work provides a broader view of the dynamic changes of the melon transcriptome triggered by FOM1.2 and highlights that the resistance response of NAD is mainly signaled by jasmonic acid and ethylene pathways mediated by ABA and auxin. The role of candidate plant and fungal responsive genes involved in the resistance is discussed.


Birth weight and body fat mass in adults assessed by bioimpedance in the ELSA-Brasil study.
Intrauterine life is a critical period for the development of body fat and metabolic risk. This study investigated associations between birth weight and total and truncal body fat in adults. To do so, we analyzed data on 10,011 adults participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who self-reported birth weight as < 2.5kg, 2.5-4.0kg, or > 4.0kg at baseline (2008-2010) and underwent bioimpedance in the next follow-up visit (2012-2014). Greater mean total and truncal fat mass were seen in those with high birth weight compared with adequate birth weight (p < 0.001) in both sexes (total fat: 25.2 vs. 23.1kg in men and 31.4 vs. 27.7kg in women, and truncal fat: 13.5 vs. 12.4kg in men and 15.9 vs. 14.2kg in women). U-shaped patterns were observed in restricted cubic-spline analyses in the subset of 5,212 individuals reporting exact birth weights, although statistically significant only for those with high birth weight. In the whole sample, in comparing high to adequate birth weight, the latter predicted having a large (> 85 percentile) total and truncal fat mass, respectively: OR = 1.76, 95%CI: 1.37-2.25 (men) and OR = 1.86, 95%CI: 1.42-2.44 (women); OR = 1.68, 95% CI: 1.31-2.16 (men) and OR = 1.73, 95%CI: 1.31-2.28 (women). However, low birth weight predicted having a large (> 85 percentile) % truncal fat only in women (OR = 1.40, 95%CI: 1.03-1.91). In conclusion, in these men and women born in a period in which fetal malnutrition was prevalent, birth weight showed complex, frequently non-linear associations with adult body fat, highlighting the need for interventions to prevent low and high birth weight during pregnancy.


Photocatalytic Nanosheet Lithography: Photolithography based on Organically Modified Photoactive 2D Nanosheets.
Harvesting the properties of nanosheets is not only crucial from a fundamental perspective, but also for the development of novel functional devices based on 2D nanosheets. Herein, we demonstrate the processing of organically modified TBAx H1-x Ca2 Nb3 O10 nanosheets into photonic thin films and study their colorimetric sensing properties in response to various aqueous and organic solvent vapors. Building on the enhanced solvent accessibility of TBA-containing nanosheets and their photocatalytic activity under UV irradiation, we develop a new concept for photocatalytic lithography using TBAx H1-x Ca2 Nb3 O10 nanosheets as a negative photoresist to obtain high-fidelity micron-scale patterns of robust inorganic nanosheets. Photocatalytic nanosheet lithography (PNL) therefore adds a new resist-free, resource efficient direct patterning technique to the toolbox of photolithography.