Antitumor, hematostimulative and radioprotective action of water-soluble derivative of propolis (WSDP).
Several studies suggest that dietary supplementation with antioxidant can influence the response to chemotherapy as well as the development of adverse side effects caused by treatment with chemotherapeutic agents. Using CBA mouse model, we investigated a clinically potential use of a water-soluble derivative of propolis (WSDP) in the treatment of various cytopenias induced by radiation and/or chemotherapy. Also, the antimetastatic efficiency of WSDP given intraperitoneally alone or in combination with chemotherapeutic agents and their effects on the blood leukocytes count as well as on hematopoiesis were studied. Tumor was a transplantable mammary carcinoma (MCa) of CBA mouse. Metastases in the lung were generated by injecting viable tumor cells intravenously (iv). WSDP (50 or 150 mg/kg) exerted a significant antimetastatic effect (P < 0.001) when given either before or after tumor cell inoculation. In combined treatment WSDP and Epirubicin profoundly inhibited metastasis formation; this synergistic effect is maximal when Epirubicin and WSDP were administrated after tumor cell inoculation. Positive outcome of combined treatment with WSDP and Epirubicin was also found regarding the number of red and white blood cells in peripheral blood while in mice treated with Epirubicin alone the significant drop in all hematological parameters was noticed on day 13 after tumor cell inoculation. Furthermore, when WSDP (50 mg/kg) was given perorally (po) for 20 consecutive days an increased number of exogenous CFUs was found in treated mice. WSDP given either for 20 or 40 days increased cellularity of hematopoietic tissue and the number of leucocytes in peripheral blood; prolonged treatment with WSDP also elevated myeloid and megakaryocytic types of CFUs. To conclude, these findings indicate that the combination of WSDP with chemotherapeutics could increase the antimetastatic potential of chemotherapeutic agents; these findings suggest the benefits of potential clinical trials using WSDP combined with chemotherapeutic agents in order to maximize their antitumor activity and minimize postchemotherapeutic or radiotherapeutic deteriorated reactions.


Functional effects of chimeric antigen receptor co-receptor signaling domains in human regulatory T cells.
Antigen-specific regulatory T cells (Tregs) engineered with chimeric antigen receptors (CARs) are a potent immunosuppressive cellular therapy in multiple disease models and could overcome shortcomings of polyclonal Treg therapy. CAR therapy was initially developed with conventional T cells, which have different signaling requirements than do Tregs To date, most of the CAR Treg studies used second-generation CARs, encoding a CD28 or 4-1BB co-receptor signaling domain and CD3ζ, but it was not known if this CAR design was optimal for Tregs Using a human leukocyte antigen-A2-specific CAR platform and human Tregs, we compared 10 CARs with different co-receptor signaling domains and systematically tested their function and CAR-stimulated gene expression profile. Tregs expressing a CAR encoding CD28wt were markedly superior to all other CARs tested in an in vivo model of graft-versus-host disease. In vitro assays revealed stable expression of Helios and an ability to suppress CD80 expression on dendritic cells as key in vitro predictors of in vivo function. This comprehensive study of CAR signaling domain variants in Tregs can be leveraged to optimize CAR design for use in antigen-specific Treg therapy.


Growth and residual stresses of arterial walls.
Growth, residual stresses and mechanical responses of arterial walls under the inner pressure are investigated within the framework of a finite deformation hyper-elasticity theory. A biomechanical model for a two-layer thick-walled circular cylindrical tube is proposed to address the mechanical effects of finite volumetric growth and residual stresses of arterial walls. The active stress due to smooth muscle tone in the media and the dispersion of collagen fiber orientations in the adventitia are also considered. The fields of displacements and stress distributions of arterial walls with growth are solved analytically. Analysis of axial, radial and circumferential growth is considered and residual stress distributions of arterial walls in different cases of growth are compared.


Static and dynamic analysis of sulfamethoxazole using GO/ZnO modified glassy carbon electrode by differential pulse voltammetry and amperometry techniques.
Surface water contamination of sulfamethoxazole (SMX) has tremendously affected the ecosystem. A primary study was performed to develop an electrochemical sensor for the determination of SMX. Overcoming the demerit associated with the conventional techniques, an electrochemical method was developed using GO/ZnO nanocomposite modified electrode to detect SMX in 0.1 M phosphate buffer (pH-5.5) buffer solution. The GO, ZnO and GO/ZnO nanocomposite were prepared using modified Hummer's, precipitation and sonochemical methods, respectively. Physico-chemical properties of all the materials and its modified electrode were analysed. Comparison was made by studying the SMX sensing performance of electrodes modified with GO, ZnO and GO/ZnO nanocomposites. Out of which GO/ZnO nanocomposite exhibited excellent sensing performance with the concentration range from 0.10 × 10-6 to 1.5 × 10-6 M with the limit of detection (LOD) 28.9 nM. The parameters such as electrolyte, effect of pH, scan rate were optimized for effective sensing performance. From the optimized results 0.1 M phosphate buffer was found to be a suitable electrolyte and the pH 5.5 was found to be appropriate to sense SMX at the scan rate 50 mVs-1. Under optimized condition, the Differential Pulse Voltammetry (DPV) and Amperometry techniques were adopted for electrochemical sensing of SMX under static and hydrodynamic condition. The developed method was successfully tested for real time analysis for the samples collected from waste water treatment plant.


Opening wedge high tibial osteotomy: plate position and biomechanics of the medial tibial plateau.
To ascertain whether changing position and size of the spacer may modify the load and displacement of the tibial plateau when performing an opening wedge high tibial osteotomy. Fifteen sawbones tibia models were used. In the axial plane, the anterior, medial, and posterior thirds of the tibial plateau were marked, and the medial and posterior thirds were called "point 1" and "point 2", respectively. A 7.5-mm-stainless steel indenter was used to apply the load over these two points: the load applied to point 1 simulated the load to that site when the knee was extended, and the load to point 2 simulated the load to the same area when the knee was flexed. Maximum load (N) and displacement (mm) were calculated. The system was shown to withstand higher loads with less displacement when the plate was posterior than it could do with the plate in the middle position. Significant differences were also found when comparing the anterior and middle position of the plate with the greatest displacement when the plate was anterior. The differences were increased when comparing the anterior and posterior positions of the plate. No statistical differences (n.s.) were found when using different spacers. The maximum stiffness was achieved if the plate was posterior and in point 1 indenter position, in which the force vector stands on the points of the lateral and medial supports (Fμ = 198.8 ± 61.5 N). The lowest stiffness was observed when the plate was anterior, and the force was applied to point 2 (Fμ = 29.7 ± 5.1 N). Application of the plate in a more posterior position provides greater stability.


Boron-containing compounds on neurons: Actions and potential applications for treating neurodegenerative diseases.
Boron-containing compounds (BCC) exert effects on neurons. After the expanding of both the identification and synthesis of new BCC, novel effects in living systems have been reported, many of these involving neuronal action. In this review, the actions of BCC on neurons are described; the effects have been inferred by boron deprivation or addition. Also, the effects can be related to those mediated by interaction on ionic channels, G-protein coupled receptors, or other receptors exerting modification on neuronal behavior. Additionally, BCC have exhibited effects by the modulation of inflammation or oxidative processes. BCC are expanding as drugs. Deprivation of boron sources from the diet shows the role of some natural BCC. However, the observations of several new synthesized compounds suggest their ability to act with attractive potency, efficacy, and long-term action on neuronal receptors or processes related with the origin and evolution of neurodegenerative processes. The details of BCC-target interactions are currently being elucidated in progress, as those observed from BCC-protein crystal complexes. Taking all of the above into account, the expansion is presumably near to having studies on the application of BCC as drugs on specific targets for treating neurodegenerative diseases.


Dynapenic obesity and the effect on long-term physical function and quality of life: data from the osteoarthritis initiative.
Obesity is associated with functional impairment, institutionalization, and increased mortality risk in elders. Dynapenia is defined as reduced muscle strength and is a known independent predictor of adverse events and disability. The synergy between dynapenia and obesity leads to worse outcomes than either independently. We identified the impact of dynapenic obesity in a cohort at risk for and with knee osteoarthritis on function. We identified adults aged ≥ 60 years from the Osteoarthritis Initiative. Obesity was defined as a body mass index ≥ 30 kg/m(2). Dynapenia was classified using the lowest sex-specific tertile of knee extensor strength. Participants were grouped according to obesity and knee strength: dynapenic obesity; dynapenia without obesity; obesity without dynapenia; and no dynapenia nor obesity. Four-year data was available. Self-reported activities of daily living (ADL) were assessed at follow-up. Outcomes of gait speed, 400 m walk distance, Late-life Disability and Function Index (LLFDI), and Short-Form (SF)-12 were analyzed using mixed effects and logistic regression models. Of 2025 subjects (56.3 % female), mean age was 68.2 years and 182 (24.1 %) had dynapenic obesity. Dynapenic obesity was associated with reduced gait speed, LLFDI-limitations, and SF-12 physical score in both sexes and in the 400 m walk in men only (all p < 0.001). A time*group interaction was significant for dynapenic obese men in the 400 m walk distance only. Odds of ADL limitations in dynapenic obesity was OR 2.23 [1.42:3.50], in dynapenia 0.98 [0.66:1.46], and in obesity 1.98 [1.39:2.80] in males. In females, odds were 2.45 [1.63:3.68], 1.60 [1.15:2.22], and 1.47 [1.06:2.04] respectively. Dynapenic obesity may be a risk factor for functional decline suggesting the need to target subjects with low knee strength and obesity.


Effectiveness of statins in patients with stroke due to cervical artery dissection: A preliminary study.
Statin therapy has become one of the most important advances in stroke secondary prevention. Nevertheless, statin therapy in patients who present an ischemic stroke following cervical artery dissection (CAD) has not yet been supported by clinical evidence. This study aimed to investigate the effect of statins on neurological outcomes after a stroke due to CAD. We conducted a prospective cohort study including consecutive patients diagnosed with a stroke due to CAD. Subjects were classified into non-statin, simvastatin 20mg, simvastatin 40mg, and high-potency statin groups. After 2 years, the functional outcome, stroke recurrence, major cardiovascular events, and mortality were assessed. Among the 54 patients included in our cohort, there were 16 (29.6%) patients without statins, 22 (40.7%) with simvastatin 20mg, 12 (22.2%) with simvastatin 40mg and 4 (7.5%) with high-potency statins. Using simvastatin 40mg was associated with a significantly lower incidence of stroke recurrence. Patients with simvastatin 40mg and high-potency statins presented the best functional recovery throughout the follow-up (p<.01). The use of statins in patients with CAD-related stroke may improve functional outcomes in specific cases. Statins do not prevent stroke recurrence and major cardiovascular events in this type of stroke.


Novel TGF-β1 inhibitor antagonizes TGF-β1-induced epithelial-mesenchymal transition in human A549 lung cancer cells.
Transforming growth factor β1 (TGF-β1), a multifunctional cytokine, is known to promote tumor invasion and metastasis and induce epithelial-mesenchymal transition (EMT) in various cancer cells. Inhibition of TGF-β1 signaling is a new strategy for cancer therapy. Most cancer cells display altered or nonfunctional TGF-β1 signaling; hence, TGF-β1 inhibitors exert limited effects on these cells. Recent studies have suggested that developing a TGF-β1 inhibitor from natural compounds is a key step to create novel therapeutic agents. This study aimed to develop a new anti-TGF-β1 therapy for cancer. We found an improved analog of chalcones, compound 67, and investigated its effects in vitro. We demonstrated the inhibitory role of compound 67 through migration and invasion assays on TGF-β1-induced EMT of human A549 lung cancer cells. Compound 67 inhibited TGF-β1-induced smad2 phosphorylation, suppressed TGF-β1-induced EMT markers, matrix metalloproteinase-2 (MMP-2) and MMP-9, and inhibited migration and invasion of A549 cells. The study results showed that compound 67 is useful to prevent tumor growth and metastasis.


The US FDAs withdrawal of the breast cancer indication for Avastin (bevacizumab).
On November 18, 2011, the US Food and Drug Administration (US FDA) announced that breast cancer indication for Avastin (bevacizumab) had been withdrawn after concluding that the drug has not been shown to be safe and effective for the treatment of breast cancer. The specific indication that was withdrawn was for the use of bevacizumab in metastatic breast cancer, with paclitaxel for the treatment of patients who have not received chemotherapy for metastatic HER2-negative breast cancer. The US FDAs decision has been met with emotion and confusion among the public and health professionals. The purpose of this article is to review the regulatory history of bevacizumab for breast cancer and to examine the scientific evidence that led to the approval and subsequent withdrawal of this indication. Bevacizumab also provides the opportunity to illustrate the value of free publicly available US FDA reviews that may contain rigorously reviewed unpublished data and analyses and to contrast the decisions made in the US and Europe about bevacizumab and breast cancer.


Mediators involved in the cancer anorexia-cachexia syndrome: past, present, and future.
The cachectic syndrome, characterized by a marked weight loss, anorexia, asthenia, and anemia is invariably associated with the presence and growth of the tumor and leads to a malnutrition status due to the induction of anorexia or decreased food intake. In addition, the competition for nutrients between the tumor and the host leads to an accelerated starvation state, which promotes severe metabolic disturbances in the host, including hypermetabolism, which leads to an increased energetic inefficiency. Although the search for the cachectic factor(s) started a long time ago, and although many scientific and economic efforts have been devoted to its discovery, we are still a long way from knowing the whole truth. Present investigation is devoted to revealing the different signaling pathways, in particular transcriptional factors involved in muscle wasting. The main aim of the present review is to summarize and evaluate the different molecular mechanisms and catabolic mediators (both humoral and tumoral) involved in cancer cachexia since they may represent targets for future promising clinical investigations.


An Overview of Pharmacologic Management of Chronic Pain.
Patients with chronic pain can be challenging to manage and historically providers have relied on opiates to treat pain. Recent studies have brought into question the safety and efficacy of chronic opiate therapy in the noncancer population. There is a vast amount of literature to support the use of nonsteroidal anti-inflammatory medications, antidepressants, anticonvulsants, topical agents, cannabinoids, and botulinum toxin either in conjunction with or in lieu of opioids. Intrathecal drug delivery systems can deliver some of these medications directly to their primary site of action while minimizing the side effects seen with systemic administration.


N-acetyl-l-cysteine and alpha lipoic acid are protective supplement on human sperm parameters in cryopreservation of asthenoteratozoospermia patients.
The aim of this study is to evaluate the beneficial effects of N-acetyl-cysteine (NAC), alpha lipoic acid (ALA) and combination of NAC + ALA supplement in freezing medium on Sperm structural and functional in asthenoteratozoospermia patients. Thirty freshly ejaculated semen samples were cryopreserved with sperm freezing medium (SFM) as control group and three group that SFM supplemented with NAC, ALA and their combination NAC+ ALA. The sperm samples were analysed according to WHO. Mitochondrial membrane potential (MMP), acrosome reaction (AR), antioxidant enzymes and DNA fragmentation were assessed using by Rhodamine123, PSA- FITC ELISA and TUNEL staining respectively. Expression level of NRF2 was assessed by real-time PCR assay. NAC and ALA alone significantly improved sperm motility, viability and DNA fragmentation (p < 0.05). MMP increased in NAC and ALA separately (p < 0.05). While did not affect the amount of sperm morphology and AR (p > 0.05). Antioxidant enzymes significantly difference in NAC and ALA groups (p < 0.05). In addition, NAC and ALA groups showed a significantly higher expression of NRF2 gene compared with other groups (p < 0.05). Our results revealed that the ALA and NAC supplements had a protective effect in cryopreservation process on the structural and functional characteristics of sperm.


An improved objective slit-lamp fluorophotometer using tungsten-halogen lamp excitation and synchronous detection.
A new design of fluorophotometer is described. The instrument can measure lower concentrations of fluorescent dye with greater accuracy than previous models.


Acetylsalicylic acid induces programmed cell death in Arabidopsis cell cultures.
Acetylsalicylic acid (ASA), a derivative from the plant hormone salicylic acid (SA), is a commonly used drug that has a dual role in animal organisms as an anti-inflammatory and anticancer agent. It acts as an inhibitor of cyclooxygenases (COXs), which catalyze prostaglandins production. It is known that ASA serves as an apoptotic agent on cancer cells through the inhibition of the COX-2 enzyme. Here, we provide evidences that ASA also behaves as an agent inducing programmed cell death (PCD) in cell cultures of the model plant Arabidopsis thaliana, in a similar way than the well-established PCD-inducing agent H(2)O(2), although the induction of PCD by ASA requires much lower inducer concentrations. Moreover, ASA is herein shown to be a more efficient PCD-inducing agent than salicylic acid. ASA treatment of Arabidopsis cells induces typical PCD-linked morphological and biochemical changes, namely cell shrinkage, nuclear DNA degradation, loss of mitochondrial membrane potential, cytochrome c release from mitochondria and induction of caspase-like activity. However, the ASA effect can be partially reverted by jasmonic acid. Taking together, these results reveal the existence of common features in ASA-induced animal apoptosis and plant PCD, and also suggest that there are similarities between the pathways of synthesis and function of prostanoid-like lipid mediators in animal and plant organisms.


Children overclaim more knowledge than adults do, but for different reasons.
Overclaiming is the phenomenon whereby people claim more knowledge of a topic than they actually have. In adults, this behavior is related to the extent to which they consider themselves an expert on that topic and may be related to impression management. We investigated the emergence of this phenomenon by developing a child-friendly overclaiming questionnaire (OCQ)-the Child-OCQ. We measured the tendency of children (5-10 years of age old; N = 94) to claim knowledge of items that did not exist for a variety of topics (places, characters, animals, food, and musical instruments). We also examined the relationship between children's overclaiming of knowledge and their self-perceived liking of, and expertise in, the topics. To validate our scale, an adult sample (N = 51) completed both the Child-OCQ and a standardized adult OCQ, the OCQ-150, showing similar overclaiming patterns on both measures. Although overclaiming behaviors decreased throughout childhood, even children as old as 10 years were not adult-like and were more likely to overclaim knowledge than adults. In addition, we did not find strong evidence that children's perceived expertise on a topic influenced their tendency to overclaim knowledge, suggesting that the mechanisms behind the overclaiming phenomenon are different in children and do not reflect impression management until later during adolescence or adulthood.


Prediction of fetal anemia by different thresholds of MCA-PSV and Delta-OD in first and second intrauterine transfusions.
Our aim was to compare different thresholds of middle cerebral artery peak systolic velocity (MCA-PSV) and amniotic fluid delta optical density (Delta-OD) with fetal hemoglobin (Hb) during first and second intrauterine transfusions (IUT). We determined serial MCA-PSV and Delta-OD in 27 red blood cell alloimmunized fetuses who needed IUT. Before the second IUT, MCA-PSV was measured. The sensitivity and specificity of MCA-PSV and Delta-OD were calculated and compared with fetal hemoglobin levels. From 27 fetuses, first time IUT MCA-PSV with a normal median value (MOM) cutoff of > 1.29 detected 60% of the moderate and 100% of the severe anemia cases. MCA-PSV of MOM > 1.5 detected none of the moderate and 93% of severe anemia cases. Delta-OD detected 50% of moderate anemic and 80% of severe anemic cases. At the second IUT, 91% of severe anemia cases were confirmed by MCA-PSV with MOM > 1.5 whereas MCA-PSV with MOM > 1.29 confirmed all cases. One case of moderate anemia was de-tected by MCA-PSV of MOM > 1.29 and none were detected by MCA-PSV with MOM > 1.5. Different thresholds of MCA-PSV have higher sensitivity and specificity for detecting moderate and severe fetal anemia compared with Delta-OD. It also has a high sensitivity at the second IUT.


Modulation of connexon densities in gap junctions of horizontal cell perikarya and axon terminals in fish retina: effects of light/dark cycles, interruption of the optic nerve and application of dopamine.
In the fish retina, connexon densities of gap junctions in the outer horizontal cells are modulated in response to different light or dark adaptation times and wavelengths. We have examined whether the connexon density is a suitable parameter of gap junction coupling under in situ conditions. Short-term light adaptation evoked low connexon densities, regardless of whether white or red light was used. Short-term dark adaptation evoked high connexon densities; this was more pronounced in the axon terminal than in perikaryal gap junctions. Under a 12 h red light/12 h dark cycle, a significant difference in connexon densities between the light and the dark period could be established in the gap junctions of the perikarya and axon terminals. Under a white light/dark cycle, only the gap junctions of axon terminals showed a significant difference. Crushing of the optic nerve resulted in an increase in connexon densities; this was more pronounced in axon terminals than in perikarya. Dopamine injected into the right eye of white-light-adapted animals had no effect. However, dopamine prevented the effect of optic-nerve crushing on connexon density. The reaction of axon-terminal gap junctions to different conditions thus resembles that of perikaryal gap junctions, but is more intense. Axon terminals are therefore thought to play an important role in the adaptation process.


Prospective evaluation of the pancreatic secretion of immunoreactive carcinoembryonic antigen, enzyme, and bicarbonate in patients suspected of having pancreatic cancer.
We undertook to test the recent suggestion that measurement of immunoreactive carcinoembryonic antigen (CEA) in pancreatic secretion may be useful in diagnosis of pancreatic cancer. Using duodenal intubation and a perfusion method in 57 cases, we measured the rate of pancreatic CEA secretion into the duodenum under basal saline perfusion, alone and with continuous intravenous infusion of secretin (2 clinical units per kg per hr) and of cholecystokinin-pancreozymin (CCK, 15 Crick-Harper-Raper units per kg per hr); and we compared the CEA output with secretion of trypsin, lipase, and bicarbonate under the same conditions. Subsequent laparotomy revealed pancreatic carcinoma in 25 patients, pancreatitis in 7, other intraabdominal malignancies in 6, and benign nonpancreatic disorders in 19. CEA output rates did not differentiate all pancreatic-cancer patients from other patients in any test condition. However, pancreatic enzyme outputs were abnormal with almost 90% of cancers of the pancreatic head and with 75% of cancers of the pancreatic body and tail. For detection of pancreatic cancer, enzyme and bicarbonate outputs in response to CCK are more accurate than pancreatic CEA or bicarbonate outputs in response to secretin. Since CCK-stimulated enzyme outputs can be related accurately to malabsorption (not reported here), we prefer them to bicarbonate output for assessment of pancreatic function.


Slower nutrient stream suppresses Subarctic Atlantic Ocean biological productivity in global warming.
Earth system models (ESMs) project that global warming suppresses biological productivity in the Subarctic Atlantic Ocean as increasing ocean surface buoyancy suppresses two physical drivers of nutrient supply: vertical mixing and meridional circulation. However, the quantitative sensitivity of productivity to surface buoyancy is uncertain and the relative importance of the physical drivers is unknown. Here, we present a simple predictive theory of how mixing, circulation, and productivity respond to increasing surface buoyancy in 21st-century global warming scenarios. With parameters constrained by observations, the theory suggests that the reduced northward nutrient transport, owing to a slower ocean circulation, explains the majority of the reduced productivity in a warmer climate. The theory also informs present-day biases in a set of ESM simulations as well as the physical underpinnings of their 21st-century projections. Hence, this theoretical understanding can facilitate the development of improved 21st-century projections of marine biogeochemistry and ecosystems.


Multiline chemical-shift (MULCH) imaging.
A fast chemical-shift imaging technique is presented. The method involves saturating all spins outside a plane, selectively exciting individual lines, phase encoding along each line, sampling the FID without gradients, and interleaving interrogation of multiple lines. A 64 X 64 array of spectra with 5 Hz resolution can be obtained in 17 min.


PET/CT in nuclear endocrinology: Results of the survey diffused through different social networks of the SEMNIM in Spain.
To know the current use of the PET/CT technology applied in the field of endocrinology, the Endocrinology Working Group of SEMNIM proposed conducting a survey. The objective was to obtain a snapshot of the use of PET/CT in nuclear endocrinology, to know if it is being used properly and detect possible needs. During the first quarter of 2022, we analyzed the data obtained from a survey that was distributed through different social networks throughout the second half of 2021. The survey asked for the use of the different PET/CT techniques available in Spain in different endocrinological pathologies like differentiated thyroid carcinoma, medullary thyroid carcinoma, neuroendocrine tumors and hyperparathyroidism. A total of 15 centers responded to the survey. A percentage of 79 of hospitals used 18F-FDG PET/CT in the diagnosis and/or follow-up of differentiated thyroid carcinoma (mean annual studies: 36.9; range 10-100); 85% used 18F-DOPA PET/CT for the study of biochemical recurrence of medullary thyroid carcinoma (mean annual studies: 7.8; range 2-20); 77% used 18F-DOPA PET/CT for the study of neuroendocrine tumors: 77% used 18F-DOPA PET/CT (mean of 10 scans per year; range 2-30) and 69% used 68Ga-DOTA-SA (mean of 24.7 studies per year; range 2-127); 79% used 18F-choline PET/CT for the study of hyperparathyroidism (mean of 30.1 annual studies; range 10-120). We detected that the use of the PET/CT technique in endocrinology is not yet widespread, however, we saw that the indications in which it is used are, in general, those reported in the different consensus.


Fractional order implementation of Integral Resonant Control - A nanopositioning application.
By exploiting the co-located sensor-actuator arrangement in typical flexure-based piezoelectric stack actuated nanopositioners, the polezero interlacing exhibited by their axial frequency response can be transformed to a zero-pole interlacing by adding a constant feed-through term. The Integral Resonant Control (IRC) utilizes this unique property to add substantial damping to the dominant resonant mode by the use of a simple integrator implemented in closed loop. IRC used in conjunction with an integral tracking scheme, effectively reduces positioning errors introduced by modelling inaccuracies or parameter uncertainties. Over the past few years, successful application of the IRC control technique to nanopositioning systems has demonstrated performance robustness, easy tunability and versatility. The main drawback has been the relatively small positioning bandwidth achievable. This paper proposes a fractional order implementation of the classical integral tracking scheme employed in tandem with the IRC scheme to deliver damping and tracking. The fractional order integrator introduces an additional design parameter which allows desired pole-placement, resulting in superior closed loop bandwidth. Simulations and experimental results are presented to validate the theory. A 250% improvement in the achievable positioning bandwidth is observed with proposed fractional order scheme.


Changes of NOx in urban air detected with monitoring VIS-NIR field spectrometer during the coronavirus pandemic: A case study in Germany.
The global outbreak of the coronavirus pandemic has led to a significant reduction of traffic and traffic-related urban air pollution. One important pollutant in this context is NO2. Sudden change in NO2 emissions related to reduction of urban traffic due to infection protection measures can be detected in Düsseldorf, Germany with continuous measurements of down-welling light with a RoX automated field-spectrometer. In comparison to a nearby reference instrument, a waveband around 590 nm was identified as significant for the retrieval in the VIS-NIR spectral range. A decision tree based on principal components which were decomposed from down-welling radiance spectra has been the most robust approach to retrieved NO2 values. Better differentiation of the NO2 value-range is achieved with a partial least square regression model. The results suggest that traffic-related changes of NOx pollution in urban air can be detected through continuous down-welling radiance measurements with inexpensive automated field-spectrometer systems.


Draft Genome Sequences of Vibrio cholerae O1 ElTor Strains 2011EL-301 and P-18785, Isolated in Russia.
We report the draft whole-genome sequences of two Vibrio cholerae O1 strains, the environmental toxigenic strain 2011EL-301 and the clinical nontoxigenic strain P-18785, both isolated in Russia. Some basic data comparing the two against the GenBank repository are provided.


Impact of blocking and detection chemistries on antibody performance for reverse phase protein arrays.
Careful selection of well-qualified antibodies is critical for accurate data collection from reverse phase protein arrays (RPPA). The most common way to qualify antibodies for RPPA analysis is by Western blotting because the detection mechanism is based on the same immunodetection principles. Western blots of tissue or cell lysates that result in single bands and low cross-reactivity indicate appropriate antibodies for RPPA detection. Western blot conditions used to validate antibodies for RPPA experiments, including blocking and detection reagents, have significant effects on aspects of antibody performance such as cross-reactivity against other proteins in the sample. We have found that there can be a dramatic impact on antibody behavior with changes in blocking reagent and detection method, and offer an alternative method that allows detection reagents and conditions to be held constant in both antibody validation and RPPA experiments.


Controlled Cyclophotocoagulation with diode laser in refractory glaucoma and long term follow up at King Abdulaziz University Hospital, Riyadh.
To evaluate the clinical efficacy and safety of controlled contact transscleral diode laser Cyclophotocoagulation (COCO) procedure in reducing the Intraocular Pressure (IOP) among patients with refractory glaucoma. Thirty two patients (35 eyes) with refractory glaucoma in prospective clinical studies were treated with trans-sclera diode laser in a controlled manner. The energy power used was 5 W in adults and 3 W in children, exposure time was 0.5 s, a total of 16 shots were applied over ciliary body and four shots in each quadrant. Pre and postoperative IOP were measured at different postoperative visits. Snellen visual acuity, the number of anti-glaucoma medications and associated complications were also recorded. Student T test was used to compare the pre and post intervention IOPs, while Wilcoxon Signed Ranks test was used, to detect significance change in medication dependency. The mean (SD) follow up time was 80.2(±9.6) months, range (36-84) m, where the mean IOP was significantly reduced from 35.1 mm Hg (±10.7) before intervention to 18.8 mm Hg (±7.3) after intervention, in the final visit (P < 0.0001). Complete success was achieved in seven eyes (20%), 22 eyes (62.8%) showed qualified successes and complete failure was reported in six eyes (17.1%). The overall success rate was 82.8% (95% CI: 70.4-95.3). Visual acuity improved in three eyes (8.5%), no change took place in 27 eyes (77.1%) and decreased in five eyes (14.2%). The number of anti-glaucoma medications has significantly changed between pre and post intervention (P < 0.0001). No cases of hypotony, phthisis bulbi or sympathetic ophthalmia were reported. Controlled COCO is a simple procedure, safe with minimal complications and fewer side effects.


MOSAICS: A software suite for analysis of membrane structure and dynamics in simulated trajectories.
Molecular dynamics (MD) simulations have become the predominant computational analysis method in membrane biophysics, as this technique is uniquely suited for investigations of complex molecular systems through the relevant physical principles. Owing to continued improvements in scope and performance, the trajectories generated through this approach contain ever-increasing amounts of information, which must be synthesized and simplified in post-analysis using tools that are not only mechanistically insightful but also computationally efficient and highly scalable. Here, we introduce MOSAICS, a self-contained high-performance suite of C++ software tools designed for advanced analyses of lipid bilayer structure and dynamics from MD trajectories. MOSAICS is to our knowledge the most comprehensive software suite of this kind, enabling analysis of a wide array of morphological and kinetic properties, for both simple and complex membranes, irrespective of system size or resolution. Importantly, MOSAICS is designed to provide spatial distributions of all computed quantities, with built-in masking tools, noise filtering, and statistical significance metrics to facilitate quantitative interpretations of the trajectory data; it is also fully parallelized and can therefore leverage the capabilities of supercomputing facilities. Despite its technical sophistication, MOSAICS is user-friendly and requires minimal computational expertise, making it accessible to researchers of all skill levels. This sofware suite can be freely downloaded at https://github.com/MOSAICS-NIH/.


Calcifying aponeurotic fibroma: a clinicopathologic study of 22 cases arising in uncommon sites.
Calcifying aponeurotic fibroma is a rare soft tissue tumor that primarily occurs in children and adolescents and has a strong predilection for the distal portion of the extremities, especially the hands and feet. This report describes 22 previously unpublished cases arising in uncommon sites. Fifteen patients were male, and seven were female (age range, 2 to 43 years; median age, 9 years). The process typically presented as a painless mass and was present from 2 weeks to 11 years before resection. Sites of involvement were the back (n=8), knee region (n=5), thigh (n=3), forearm (n=3), elbow (n=2), and arm, not otherwise specified (n=1). The lesions were often adherent to dense fibrous connective tissue (eg, tendon, fascia, or periosteum) and ranged from 1.0 to 5.0 cm in maximum dimension. The process typically had an irregular contour and a firm, fibrous consistency. Sometimes minute foci with a calcific appearance were evident grossly. Microscopic examination showed spindled fibroblasts with a fascicular growth pattern and scattered epithelioid cells bordering chondroid foci with or without mineralization. Immunoreactivity was present for vimentin (six of six), muscle-specific actin (three of six), smooth muscle actin (three of six), CD99 (five of five), CD34 (one of six), CD57 (one of six, trace), EMA (two of six, trace), S100 protein (five of six), CD68 (five of five), and progesterone receptor (one of six). The tumors were managed by local excision (n=20), incomplete local excision (n=1) and biopsy only (n=1). Follow-up information was available for 10 patients with a median follow-up interval of 94 months. Five patients (50%) developed one or more recurrences. Familiarity with this entity should help to avoid confusion with other processes, including infantile and extraabdominal fibromatoses, a chondroma of soft parts, and a fibrous hamartoma of infancy.


Regulation of PCNA-protein interactions for genome stability.
Proliferating cell nuclear antigen (PCNA) has a central role in promoting faithful DNA replication, providing a molecular platform that facilitates the myriad protein-protein and protein-DNA interactions that occur at the replication fork. Numerous PCNA-associated proteins compete for binding to a common surface on PCNA; hence these interactions need to be tightly regulated and coordinated to ensure proper chromosome replication and integrity. Control of PCNA-protein interactions is multilayered and involves post-translational modifications, in particular ubiquitylation, accessory factors and regulated degradation of PCNA-associated proteins. This regulatory framework allows cells to maintain a fine-tuned balance between replication fidelity and processivity in response to DNA damage.


Nitric oxide in gastroprotection by sucralfate, mild irritant, and nocloprost. Role of mucosal blood flow.
Pretreatment with sucralfate is known to protect gastric mucosa against the damaging effect of strong irritants, and this protection is accompanied by an increase in mucosal blood flow but the mechanisms underlying these effects have not been elucidated. Similar gastroprotective and hyperemic effects can be obtained with exogenous prostaglandins (PG), mild irritants such as dilute ethanol, and by capsaicin. In this study we investigated the role of nitric oxide (NO) in the prevention of ethanol-induced gastric damage and gastric blood flow by sucralfate, mild irritant such as 20% ethanol, capsaicin, and nocloprost, a stable PGE2 analog. Pretreatment with NG-nitro-L-arginine (L-NNA), an inhibitor of NO synthase, enhanced ethanol-induced mucosal damage and reduced dose-dependently the gastroprotective and hyperemic effects of sucralfate, dilute ethanol, and capsaicin. The doses of L-NNA attenuating significantly the protective effects of sucralfate or 20% ethanol were 25-50 mg/kg, while those reducing the protection by capsaicin were 6.2-12.5 mg/kg. The attenuating effect of L-NNA on gastroprotection was reversed by L-arginine but not D-arginine. For comparison, the gastroprotective (but not hyperemic) effect of nocloprost was not affected by the pretreatment with L-NNA and/or arginine. We conclude that sucralfate, mild irritant, and capsaicin activate the NO system that may contribute to their gastroprotective effect through enhancing mucosal circulation but that NO is not essential for the mucosal protection by PGE2 analog.


Visemic processing in audiovisual discrimination of natural speech: a simultaneous fMRI-EEG study.
In a noisy environment, visual perception of articulatory movements improves natural speech intelligibility. Parallel to phonemic processing based on auditory signal, visemic processing constitutes a counterpart based on "visemes", the distinctive visual units of speech. Aiming at investigating the neural substrates of visemic processing in a disturbed environment, we carried out a simultaneous fMRI-EEG experiment based on discriminating syllabic minimal pairs involving three phonological contrasts, each bearing on a single phonetic feature characterised by different degrees of visual distinctiveness. The contrasts involved either labialisation of the vowels, or place of articulation or voicing of the consonants. Audiovisual consonant-vowel syllable pairs were presented either with a static facial configuration or with a dynamic display of articulatory movements related to speech production. In the sound-disturbed MRI environment, the significant improvement of syllabic discrimination achieved in the dynamic audiovisual modality, compared to the static audiovisual modality was associated with activation of the occipito-temporal cortex (MT+V5) bilaterally, and of the left premotor cortex. While the former was activated in response to facial movements independently of their relation to speech, the latter was specifically activated by phonological discrimination. During fMRI, significant evoked potential responses to syllabic discrimination were recorded around 150 and 250 ms following the onset of the second stimulus of the pairs, whose amplitude was greater in the dynamic compared to the static audiovisual modality. Our results provide arguments for the involvement of the speech motor cortex in phonological discrimination, and suggest a multimodal representation of speech units.


Dietary patterns associated with stroke among West Africans: A case-control study.
The relationship of diet with stroke risk among Africans is not well understood. The aim of this study was to investigate the association between dietary patterns and stroke risk among West Africans. In this multi-center case-control study, 3684 stroke patients matched (for age and sex) with 3684 healthy controls were recruited from Nigeria and Ghana. Food consumption was assessed using a food frequency questionnaire, and dietary patterns were summarized using principal component analysis. Stroke was defined using predefined criteria primarily on clinical evaluation following standard guidelines. Conditional logistic regression was applied to compute odds ratio (OR) and 95% confidence interval (CI) for stroke risk by tertiles of dietary patterns adjusting for relevant confounders. Overall, mean age was 59.0 ± 13.9 years, and 3992 (54.2%) were males. Seven dietary patterns were identified. Multivariable-adjusted OR (95% CI) for risk of stroke by second and third tertiles (using the lowest and first tertile as reference) of dietary patterns was 1.65 (1.43, 1.90) and 1.74 (1.51, 2.02), for "poultry product and organ meat"; 1.69 (1.47, 1.96) and 1.51 (1.31, 1.75) for "red meat"; 1.07 (0.92, 1.23) and 1.21 (1.04, 1.40) for "fried foods and sweetened drinks"; 0.69 (0.60, 0.80) and 0.45 (0.39, 0.53) for "vegetables"; 0.84 (0.72, 0.97) and 0.81 (0.70, 0.93) for "whole-grain and fruit drinks"; and 0.97 (0.84, 1.12) and 0.85 (0.73, 0.98) for "fruits" respectively (p < 0.05). These data suggest that plant-based diets are associated with a lower risk of stroke and might be a beneficial dietary recommendation for the primary prevention of stroke among Africans.


Hepatic hemangiomas: evaluation by magnetic resonance imaging and technetium-99m red blood cell scintigraphy.
A study was performed to evaluate and compare the sensitivity of magnetic resonance imaging (MRI) and radionuclide blood-pool scanning in the detection of hepatic hemangiomas. All patients had known hemangiomas which were first detected on either ultrasound or computed tomography. Sixteen patients with a total of 23 lesions were investigated. Eleven patients had both MRI and blood-pool scans performed. In the group studied by both modalities, 18 lesions were detected ranging in size from 1 to 11 cm. All lesions were detected by both techniques. However, two of the 18 lesions had an atypical appearance on MRI. Our experience to date indicates that the anatomic location and specific diagnosis of hemangiomas can be made with a high degree of certainty when both MRI and blood-pool scanning techniques are utilized.


Necitumumab plus gemcitabine and cisplatin in previously treated lung squamous cell carcinoma.
The efficacy and safety of the anti-EGFR antibody necitumumab combined with gemcitabine and cisplatin (N + GC) in the first-line treatment of advanced lung squamous cell carcinoma (LSCC) have been proven. However, the efficacy and safety of N + GC in the second line or later treatment remain unclear. Eleven patients who received N + GC for advanced-stage or recurrent LSCC were enrolled. We retrospectively assessed the patients' clinical characteristics and efficacy and safety of treatment. The median patient age was 73 years (range, 63-77 years). The cohort included nine (81.8%) men and two (18.2%) women. Two (18.2%) patients had postoperative recurrence, and one (9.1%), three (27.3%), one (9.1%), and four (36.4%) patients were diagnosed with stage IIIA, IIIB, IVA, and IVB disease, respectively. Concerning the best overall response, partial response was achieved in five (45.5%) patients, four (36.4%) patients displayed stable disease, and two (18.2%) patients were not evaluable. Median progression-free survival was 6.8 months (range, 1.4-10.3 months). The grade 3 or higher neutropenia, thrombocytopenia, and anemia occurred in six (54.5%), three (27.3%), and two (18.2%) patients, respectively. Additionally, grade 3 skin reaction, rash, lung infection, duodenal ulcer, and febrile neutropenia were observed in one (9.1%) patient each. Two (18.2%) patients required treatment interruption because of adverse events. N + GC displayed good efficacy in the second line or later treatment among patients with LSCC. This study suggested that N + GC is a useful option even after second-line treatment of advanced-stage or recurrent LSCC, although the management of adverse events is essential.


Apolipoprotein A-1 in cholestatic liver diseases.
The apolipoprotein A-1 in cholestatic liver diseases was determined by rocket immunoelectrophoresis. A decrease in the serum apo A-1 was generally observed in LP-X positive liver disease, particularly in the patients with extrahepatic biliary obstruction. With reference to LP-X levels and LCAT activity, the results indicated that not only hepatocellular damage but also cholestasis contribute to the decrease of apo A-1 concentration in patients with liver disease.


Multimorbidity and use of hypnotic and anxiolytic drugs: cross-sectional and follow-up study in primary healthcare in Iceland.
The prevalence of multimorbidity is increasing worldwide, presumably leading to an increased use of medicines. During the last decades the use of hypnotic and anxiolytic benzodiazepine derivatives and related drugs has increased dramatically. These drugs are frequently prescribed for people with a sleep disorder often merely designated as "insomnia" in the medical records and lacking a clear connection with the roots of the patients' problems. Our aim was to analyse the prevalence of multimorbidity in primary healthcare in Iceland, while concurrently investigating a possible association with the prevalence and incidence of hypnotic/anxiolytic prescriptions, short-term versus chronic use. Data were retrieved from a comprehensive database of medical records from primary healthcare in Iceland to find multimorbid patients and prescriptions for hypnotics and anxiolytics, linking diagnoses (ICD-10) and prescriptions (2009-2012) to examine a possible association. Nearly 222,000 patients, 83 % being local residents in the capital area, who contacted 16 healthcare centres served in total by 140 general practitioners, were set as a reference to find the prevalence of multimorbidity as well as the prevalence and incidence of hypnotic/anxiolytic prescriptions. The prevalence of multimorbidity in the primary care population was 35 %, lowest in the young, increasing with age up to the 80+ group where it dropped somewhat. The prevalence of hypnotic/anxiolytic prescriptions was 13.9 %. The incidence rate was 19.4 per 1000 persons per year in 2011, and 85 % of the patients prescribed hypnotics/anxiolytics were multimorbid. Compared to patients without multimorbidity, multimorbid patients were far more likely to be prescribed a hypnotic and/or an anxiolytic, OR = 14.9 (95 % CI = 14.4-15.4). Patients with multiple chronic conditions are common in the primary care setting, and prevalence and incidence of hypnotic/anxiolytic prescriptions are high. Solely explaining use of these drugs by linear thinking, i.e. that "insomnia" leads to their prescription is probably simplistic, since the majority of patients prescribed these drugs are multimorbid having several chronic conditions which could lead to sleeping problems. However, multimorbidity as such is not an indication for hypnotics, and doctors should be urged to greater caution in their prescribing, bearing in mind non-pharmacological therapy options.


Aneurysms of the pulmonary arteries--a case report.
A fifty-five-year-old male demonstrated over a three-year period marked enlargement of pulmonary aneurysms. This can be a fatal condition owing to rupture of the aneurysms.


Selection and validation of differentially expressed metabolic and immune genes in weaned Ghurrah versus crossbred piglets.
In the present investigation, differentially expressed genes (DEGs) were studied using RNA sequencing (RNA-seq) technique in porcine peripheral blood mononuclear cells (PBMC) of weaned Ghurrah and crossbred piglets at 3-month age. Transcriptomic analysis was done using three different packages, namely, EBSeq, DESeq2, and edgeR, to identify the DEGs between Ghurrah and crossbred piglets. Total 7717 DEGs were commonly identified by all three packages, out of which 4151 genes found to be up-regulated, and 3566 genes were down-regulated. Functional annotation of these DEGs indicated metabolism as the most commonly enriched category followed by the immune response. Genes related to metabolism and growth were up-regulated in crossbred piglets as compared with Ghurrah piglets, whereas immunity-related genes were up-regulated in Ghurrah piglets elucidating the disease resistance nature of this indigenous breed over crossbred counterparts. Further, eight DEGs, namely, LRP-1, ADCY4, ERRFI1, LDHD, ARG1, OASL, MGARP, and S100A8, were validated by qRT-PCR in a separate set of biological samples and found to be in concordance with RNA-seq results. Finding in the present study provides insight into genes and their molecular mechanisms governing difference in growth performance between Ghurrah and crossbred pigs.


An atypical presentation of a strangulated bochdalek hernia in a 60-year-old woman.
Bochdalek hernia (BH), resulting from the failure of posterolateral diaphragmatic foramina to fuse, is the most common congenital diaphragmatic hernia and usually manifests in pediatric age with life-threatening complications. Here, we report the case of a 60-year-old female with a left-sided Bochdalek diaphragmatic hernia, who presented with abdominal pain and dyspnea. The patient was successfully treated by open surgery approach but the patient died due to the lung doesnt expand after atelectasis in the third day after surgery. We know that a few cases of bochdalek hernia have been reported in the elderly by the medical literature, but what distinguishes our case is that the hernia was strangulated and the patient died as a result of non-expansion of the lung after its atelectasis following surgical repair.


Do all patients with advanced non-small-cell lung cancer benefit from cisplatin-based combination therapy?
Platinum-based chemotherapy has been shown to be effective in improving survival and quality of life in advanced non-small-cell lung cancer (NSCLC) patients. The objective of this study was to identify patients more likely to benefit from chemotherapy in order to avoid the indiscriminate treatment of all patients. A multivariate analysis of survival was performed using the database of the European randomized phase III trial that compared vinorelbine (navelbine) (NVB), vinorelbine-cisplatin (NVB-P) and vindesine-cisplatin (VDS-P) in 612 patients with inoperable NSCLC (stage III or IV). Interactions between treatment and the prognostic factors singled out by the Cox procedure were specifically tested. The performance status (PS) was the only significant interaction among the selected prognostic factors and treatment. Subgroup analysis showed that the advantage obtained with NVB-P predominantly concerned PS 0-1 patients, whose median survival lasted 43 weeks (95% confidence interval (95% CI): 39-50 weeks) with a one-year survival rate of 38% (95% CI: 31%-46%) versus 36 weeks (95%, CI: 30-40 weeks) and 34% (95% CI: 27%-42%) for NVB alone, and 33 weeks (95% CI: 30-39 weeks) and 29% (95% CI: 22%-36%) for VDS-P. In sharp contrast, survival in PS 2 patients was similar (median 18 weeks) (NVB-P 95% CI: 11-34 weeks; NVB 95% CI: 11-35 weeks; VDS-P 95% CI: 14-32 weeks) whatever the treatment. PS 2 patients with advanced NSCLC might not benefit from cisplatin combination therapy.


Progression of fatigue in Parkinson's disease - a 9-year follow-up.
Although highly disabling, the pathogenesis and evolution of fatigue in Parkinson's disease (PD) is largely unknown, and no sufficiently documented treatment currently exists. The aim of the present study was to investigate the evolution of fatigue during the first 9 years after diagnosis. This study is part of the Norwegian ParkWest collaboration, a prospective population-based longitudinal cohort study. The present study comprised 191 newly diagnosed patients and 170 control participants. Fatigue was assessed by the Fatigue Severity Scale, with examinations at baseline and then every other year up to 9 years of follow-up. Linear mixed models were applied to investigate possible variables associated with fatigue. It was found that there was a statistically significant increase in the proportion of PD patients with fatigue during the first 9 years after diagnosis. A large proportion of patients had a significant increase or decrease in fatigue score between consecutive visits. In addition, the relative risk of persistent fatigue and ever having fatigue was higher than for controls. There were statistically significant longitudinal associations between higher levels of fatigue and female gender, comorbidity at baseline, depressive symptoms, dependency in activities of daily living and better cognitive functioning. Lower levels of fatigue were associated with the use of dopamine agonists. Fatigue is a common, severely limiting symptom in PD. This study demonstrates associations with other factors that could yield a better understanding of the symptom and thus possible treatment strategies, although further investigations are necessary to establish causal relationships.


Ubiquitin e3 ligase itch negatively regulates osteoblast differentiation from mesenchymal progenitor cells.
Itch, a HECT family E3 ligase, affects numerous cell functions by regulating ubiquitination and proteasomal degradation of target proteins. However, the role of Itch in osteoblasts has not been investigated. We report that Itch(-/-) mice have significantly increased bone volume, osteoblast numbers, and bone formation rate. Using bone marrow stromal cells from Itch(-/-) mice and wild-type (WT) littermates as bone marrow mesenchymal precursor cells (BM-MPCs), we found that BM-MPCs from Itch(-/-) mice have compatible numbers of cells expressing mesenchymal stem cell markers. However, Itch(-/-) BM-MPCs grew faster in an in vitro culture, formed more CFU-F mesenchymal colonies, and exhibited increased osteoblast differentiation and decreased adipogenesis. Importantly, Itch(-/-) mesenchymal colony cells formed significantly more new bone in a tibial defect of recipient mice compared with WT cells. The expression levels of JunB, an AP-1 transcription factor that positively regulate osteoblast differentiation, were significantly increased in Itch(-/-) BM-MPCs when proteasome function is intact. In contrast, the amount of ubiquitinated JunB protein was markedly decreased in Itch(-/-) cells when proteasome function was blocked. Overexpression of WT Itch, but not an Itch ligase-inactive mutant, rescued differentiation defects of Itch(-/-) BM-MPCs. Itch(-/-) BM-MPCs had a similar role in immune modulation as WT cells. Thus, Itch negatively controls osteoblast differentiation from BM-MPCs through the regulation of proteasomal degradation of positive osteoblast regulator JunB protein. Itch is a potential new target for bone anabolic drug development to treat patients with bone loss.


An angiotensin-converting enzyme (ACE) polymorphism may mitigate the effects of angiotensin-pathway medications on posttraumatic stress symptoms.
Angiotensin, which regulates blood pressure may also act within the brain to mediate stress and fear responses. Common antihypertensive medication classes of angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) have been associated with lower PTSD symptoms. Here we examine the rs4311 SNP in the ACE gene, previously implicated in panic attacks, in the relationship between ACE-I/ARB medications and PTSD symptoms. Participants were recruited from outpatient wait rooms between 2006 and March 2014 (n= 803). We examined the interaction between rs4311 genotype and the presence of blood pressure medication on PTSD symptoms and diagnosis. PTSD symptoms were lower in individuals taking ACE-Is or ARBs (N = 776). The rs4311 was associated with PTSD symptoms and diagnosis (N = 3803), as the T-carriers at the rs4311 SNP had significantly greater likelihood of a PTSD diagnosis. Lastly, the rs4311 genotype modified the effect of ACE-Is or ARBs on PTSD symptoms (N = 443; F1,443 = 4.41, P < 0.05). Individuals with the CC rs4311 genotype showed lower PTSD symptoms in the presence of ACE-Is or ARBs. In contrast, T- carriers showed the opposite, such that the presence of ACE-Is or ARBs was associated with higher PTSD symptoms. These data suggest that the renin-angiotensin system may be important in PTSD, as ACE-I/ARB usage associates with lower symptoms. Furthermore, we provide genetic evidence that some individuals are comparatively more benefitted by ACE-Is/ARBs in PTSD treatment. Future research should examine the mechanisms by which ACE-Is/ARBs affect PTSD symptoms such that pharmaco-genetically informed interventions may be used to treat PTSD.


N-Ras or K-Ras inhibition increases the number and enhances the function of Foxp3 regulatory T cells.
Naturally occurring regulatory T cells (Treg) driven by their transcriptional controller Foxp3 are compromised in immune-mediated disorders and confer protection when adoptively transferred. We examined the Ras-inhibitory effect on functional determinants of Treg in vivo and in vitro. Ras was inhibited in Jurkat T cells by transfection with a dominant-negative form of Ras, or by shRNA for N-Ras, K-Ras, and H-Ras, or by farnesylthiosalycylic acid, a small-molecule inhibitor. Except for H-Ras transduction with shRNA, each inhibitory mode increased expression of Foxp3 and nuclear factor of activated T cell proteins, and surface expression of CD25. Ras inhibition in PBMC and spleen-derived lymphocytes reproduced these findings. The heightened Foxp3 expression reflected both increased basal cellular protein and peripheral conversion of non-Treg to Treg. Ras inhibition enhanced Treg-induced suppression; thus, when adoptively transferred to mice, Ras-inhibited Treg reduced the incidence of diabetes. Inhibition of Foxp3 by respective siRNA reversed the enhancement. Thus, inhibition of the N- or K-Ras isoform triggers an anti-inflammatory effect by up-regulating, via Foxp3 elevation, the numbers and functional suppressive properties of Treg.


Neurodevelopmental outcome of infants with congenital diaphragmatic hernia prospectively enrolled in an interdisciplinary follow-up program.
The purpose of the study was to evaluate the neurodevelopmental outcome in infants with congenital diaphragmatic hernia (CDH). Between June 2004 and September 2007, 41 CDH survivors were prospectively enrolled in an interdisciplinary follow-up program. Neurodevelopmental status was evaluated using the Bayley Scales of Infant Development II (prior 2006, n = 9), the Bayley Scales of Infant Development III (after 2006, n = 27), or the Wechsler Preschool and Primary Scale of Intelligence III (children older than 4 years, n = 5). Scores were grouped as average, mildly delayed, and severely delayed by standard deviation intervals (115-85, 71-84, <70), and mixed if average and mildly delayed in either cognitive or language. Median age at last assessment was 24 months (range, 6-62). Average, mixed, mildly delayed, and severely delayed scores for neurocognitive and language skills were found in 49%, 19%, 17%, and 15%, respectively. Psychomotor scores were normal, mildly delayed, and severely delayed in 46%, 23%, and 31%, respectively. Autism was present in 7%. Abnormal muscle tonicity was found in 51% (49% hypotonic, 2% hypertonic). Multivariate risk factors for borderline or delayed neurodevelopmental, neurocognitive, and/or psychomotor outcome were intrathoracic liver position (P = .02), presence of a right-sided CDH (P = .02), extracorporeal membrane oxygenation need (P < .001), Gore-Tex patch repair (P = .02), O(2) requirement at 30 days of life (P < .01), and hypotonicity (P < .01). The prospective evaluation in an interdisciplinary follow-up program uncovered striking morbidities in neurodevelopmental status in approximately half of the CDH infants. The most common neurologic sequelae are neuromuscular hypotonicity and psychomotor dysfunction. Patient-specific factors are important determinants of adverse neurologic outcome.


Enhancement of curcumin oral absorption and pharmacokinetics of curcuminoids and curcumin metabolites in mice.
Curcumin has shown a variety of biological activity for various human diseases including cancer in preclinical setting. Its poor oral bioavailability poses significant pharmacological barriers to its clinical application. Here, we established a practical nano-emulsion curcumin (NEC) containing up to 20% curcumin (w/w) and conducted the pharmacokinetics of curcuminoids and curcumin metabolites in mice. This high loading NEC was formulated based on the high solubility of curcumin in polyethylene glycols (PEGs) and the synergistic enhancement of curcumin absorption by PEGs and Cremophor EL. The pharmacokinetics of curcuminoids and curcumin metabolites was characterized in mice using a LC-MS/MS method, and the pharmacokinetic parameters were determined using WinNonlin computer software. A tenfold increase in the AUC (0→24h) and more than 40-fold increase in the C (max) in mice were observed after an oral dose of NEC compared with suspension curcumin in 1% methylcellulose. The plasma pharmacokinetics of its two natural congeners, demethoxycurcumin and bisdemethoxycurcumin, and three metabolites, tetrahydrocurcumin (THC), curcumin-O-glucuronide, and curcumin-O-sulfate, was characterized for the first time in mice after an oral dose of NEC. This oral absorption enhanced NEC may provide a practical formulation to conduct the correlative study of the PK of curcuminoids and their pharmacodynamics, e.g., hypomethylation activity in vivo.


Characteristics and Postoperative Outcomes for High Cervical versus Subaxial Cervical Intradural Extramedullary Tumors: A Multicenter Study.
High cervical intradural extramedullary tumors are uncommon. Their relationship to surrounding neural structures and vertebral arteries makes surgical excision challenging. No previous studies have compared high cervical to subaxial cervical intradural extramedullary spinal tumors to elucidate their unique characteristics and surgical outcomes. We performed a retrospective study in which patients who underwent excision of a cervical intradural extramedullary tumor were divided into a high cervical group and a subaxial cervical group. Variables included sex, age, Charlson Comorbidity Index, volume, laterality, preoperative weakness, use of neuromonitoring and drains, instrumented fusion, complications, length of stay, histology, discharge location, recurrence, and duration of follow-up. Variables were compared between the 2 groups. Limb power and Nurick classification were charted preoperatively, at discharge, and at 6 months to plot their recovery trajectory. Eighty-four patients with a total of 90 tumors were enrolled, including 40 patients in the high cervical group and 44 patients in the subaxial spine group. More patients with neurofibromas (P = 0.011) and bilateral tumors (P = 0.044) were in the high cervical group. A greater prevalence of neurofibromatosis type 1 was significant for bilateral high cervical tumors (P = 0.033). More patients in the subaxial group had instrumented fusion (P = 0.045). More patients in the high cervical group had improvement in limb power (P = 0.025) and Nurick classification (P = 0.0001) postoperatively before discharge. By 6 months, both groups had similar recovery. No mortality was attributable to surgery in either group. High cervical intradural extramedullary spine tumors have more bilateral tumors associated with neurofibromatosis type 1. Despite the challenging anatomy, surgical resection is safe with good outcomes in this group.


Characterization of epitopes of human monoclonal antibodies against cytomegalovirus glycoprotein B for neutralization and antibody-dependent phagocytosis.
As congenital cytomegalovirus (CMV) infections are the leading non-genetic cause of sensorineural hearing loss and significant neurological disabilities in children, the development of CMV vaccines should be given the highest public health priority. Although MF59-adjuvanted glycoprotein B (gB) vaccine (gB/MF59) is safe and immunogenic, its efficacy in terms of protection from natural infection was around 50 % in clinical trials. Although gB/MF59 induced high antibody titers, anti-gB antibodies contributed little to the neutralization of infection. Recent studies have found that non-neutralizing functions, including antibody-dependent phagocytosis of virions and virus-infected cells, are likely to play important roles in pathogenesis and vaccine design. Previously, we isolated human monoclonal antibodies (MAbs) that reacted with the trimeric form of gB ectodomain and found that preferential epitopes for neutralization were present on Domains (Doms) I and II of gB, while there were abundant non-neutralizing antibodies targeting Dom IV. In this study, we analyzed the phagocytosis activities of these MAbs and found the following: 1) MAbs effective for phagocytosis of the virions targeted Doms I and II, 2) the MAbs effective for phagocytosis of the virions and those of virus-infected cells were generally distinct, and 3) the antibody-dependent phagocytosis showed little correlation with neutralizing activities. Taking account of the frequency and levels of neutralization and phagocytosis, incorporation of the epitopes on Doms I and II into developing vaccines is considered desirable for the prevention of viremia.


Pegylated liposomal doxorubicin in stage IVB mycosis fungoides.
Previous studies have shown that pegylated liposomal doxorubicin (LD) is effective in the treatment of relapsing or recalcitrant cutaneous T-cell lymphoma. To evaluate the activity and toxicity of LD in patients with stage IVB mycosis fungoides (MF). In this retrospective study, we evaluated outcomes and recorded adverse effects in 10 patients with MF (seven men and three women) with extracutaneous involvement. Patients were treated with LD 20 mg m(-2) administered intravenously every 4 weeks. All patients received at least two cycles of LD, three patients received four cycles and one patient received six cycles. Three patients (30%) had a partial response and two patients had stable disease. Grade 1-2 leucopenia occurred in three of the 10 patients, and grade 4 leucopenia in one. Three patients had grade 2 palmoplantar erythrodysaesthesia. This study demonstrates that LD is beneficial in terms of activity and toxicity in stage IVB MF. These observations should be verified in larger studies.


Osteogenically-induced exosomes stimulate osteogenesis of human adipose-derived stem cells.
Exosomes exhibit great therapeutic potential in bone tissue engineering. The study aimed to investigate whether the exosomes derived from human adipose-derived stem cells (hADSCs-Exos) during different time-span of osteogenic differentiation could promote osteogenesis. The appropriate concentrations of hADSCs-Exos to enhance the proliferation, migration and osteogenesis of hADSCs-Exos were also examined. PKH67 labelled hADSCs-Exos was used to detect the internalization ability of hADSCs. The osteogenic differentiation abilities of hADSCs after treatment with hADSCs-Exos was evaluated by Alizarin red staining (ARS). The proliferation and migration of hADSCs was examined by cell counting kit-8 and wound healing assay, respectively. The expression of exosomal surface markers and osteoblast-related protein of hADSCs was assessed by Western blot. PKH67-labelled exosomes were internalized by hADSCs after 4 h incubation. ARS showed that the amount of mineralized nodules in Exo1-14d group was significantly higher than that in Exo15-28d group. hADSCs-Exos could promote the proliferation and migration capacity of hADSCs. Western blot analysis showed that after hADSCs-Exos treatment, ALP and RUNX2 were significantly enhanced. Specially, the Exo1-14d group of 15 μg/mL significantly upregulated the expression of RUNX2 than the other exosomes treated groups. Our findings suggest that exosomes secreted by hADSCs during osteogenic induction for 1-14 days could be efficiently internalized by hADSCs and could induce osteogenic differentiation of hADSCs. Moreover, administration of Exo1-14d at 15 μg/mL promoted the proliferation and migration of hADSCs. In conclusion, our research confirmed that comprised of hADSCs-Exos and hADSCs may provide a new therapeutic paradigm for bone tissue engineering.


BMI as a moderator of perceived stress and emotional eating in adolescents.
Emotional eating has often been linked to overweight and/or obesity. Multiple group SEM analyses were conducted using cross-sectional data from 517 minority students in Los Angeles County. Results showed no differences in emotional eating between normal weight and overweight students. Perceived stress was indeed a significant correlate of emotional eating, independent of BMI status, as indicated by the lack of a modifying effect of BMI status. Findings highlight the fact that emotional eating is not an issue only for overweight and obese persons. This study shows that some children in this population at increased risk for obesity and related chronic disease have already incorporated emotional eating as a learned response to stress by the time that they enter adolescence.


Dimerization of bisphenol A by hyper lignin-degrading fungus Phanerochaete sordida YK-624 under ligninolytic condition.
Bisphenol A (BPA) was treated with hyper lignin-degrading fungus Phanerochaete sordida YK-624 under ligninolytic condition. After preculturing P. sordida YK-624 for 4 days, BPA (final concentration, 1 and 0.1 mM) was added to cultures. Both 1- and 0.1-mM BPA were effectively decreased within a 24-h treatment and two metabolites were detected. Two metabolites (5,5'-bis-[1-(4-hydroxy-phenyl)1-methyl-ethyl]-biphenyl-2,2'-diol and 4-(2-(4-hydroxy-phenyl) propan-2-yl)-2-(4-(2-(4-hydroxyphenyl) propan-2-yl) phenoxy)phenol) were identified by ESI-MS and NMR analysis. These results indicated that BPA was oxidized to BPA phenoxy radicals by ligninolytic enzymes and then dimerized at extracellular region.


TRAF6 promotes the invasion and metastasis and predicts a poor prognosis in gastric cancer.
This study investigated the relationships of TRAF6 expression with clinical pathologic parameters and the prognosis of patients with gastric cancer. This study also explored the roles of TRAF6 in cell apoptosis and invasiveness, as well as underlying molecular mechanism of gastric cancer cell line in vitro. A total of 90 cases of tissue microarrays were immunohistochemically analyzed for TRAF6 expression. Cell proliferation was measured by MTT assay. Flow cytometry was used for analyzing cell apoptosis and cell invasion ability was detected by a Transwell invasion assay. Protein expression was assessed by Western blotting. TRAF6 was expressed in 53 of 90 (58.9%) cases of gastric cancer. TRAF6 expression was significantly positively correlated with advanced N stage, pathological stage and a poor prognosis, but not an independent predictor of a poor prognosis in gastric cancer (p=0.083). The knockdown of TRAF6 increased cell apoptosis and reduced invasive ability of BGC-823 cell. Moreover, TRAF6 down-regulation decreased protein levels of phosphor-Akt, Bcl-2 and MMP9 and up-regulation of Bax in BGC-823 cell. Inversely, overexpression of TRAF6 in SGC-7901 cells increased protein levels of phosphor-Akt, Bcl-2 and MMP9 and down-regulation of Bax. The expression of TRAF6 was positively correlated with an advanced N stage and acted as a predictor of a poor prognosis in patients with gastric cancer. Moreover, TRAF6 regulating cell apoptosis and invasive ability of gastric cancer cells might be associated with Akt activation and alterations of protein expression of Bcl2, Bax and MMP9.


Invasion of brain tissue by primary glioma: evidence for the involvement of urokinase-type plasminogen activator as an activator of type IV collagenase.
The immunocharacterization of a metalloproteinase isolated from rat glioma cell conditioned medium is described and confirms that the enzyme is identical to type IV collagenase. Free, active plasminogen activator (PA) and PA-PAI complexes were identified as being secreted by the same cells. Using affinity-purified metalloproteinase we demonstrate that the enzyme can be partially activated by u-PA but not by plasmin in vitro. On the basis of these findings and previous published work we propose a scheme for the proteolytic degradation of normal brain tissue during tumour invasion.


Optimal bond issuance with cost and liquidity constraints for Chinese local governments: a multi-period stochastic programming approach.
In recent years, China's local governments have issued numerous bonds to support the country's economic development. However, as total debt accumulates, the pressure on debt repayments is gradually increasing. To increase the sustainability of local government debt, we propose a multi-period stochastic optimization-based approach to determining the portfolio composition of issued bonds, with the goal of minimizing the expected cost under the constraints of liquidity risk and cost deviation risk. Liquidity risk is measured by conditional payment-at-risk ( CPaR ), and cost deviation risk is measured by conditional value-at-risk ( CVaR ). By bounding CVaR and CPaR , local governments can control the levels of cost deviation risk and liquidity risk. To alleviate future liquidity risk, which is caused by the issuance of a large number of long-term bonds to deliberately reduce repayment pressure within a debt planning horizon, we consider an extended liquidity planning horizon to manage both current and future liquidity risk. Based on this, we analyze the efficient frontier and portfolio compositions of issued bond under the constraints of different CVaR and CPaR levels. Compared with actual Chinese local government bond portfolios, the efficient frontier performs better for different issuance strategies.


Pattern of Uveitis in a Referral Hospital in Bangladesh.
To report the pattern of uveitis in a tertiary eye care center in Bangladesh. Retrospective analysis of all uveitis cases visiting uveitis clinic of Bangladesh Eye Hospital between January, 2009 and April, 2015. In total, 652 patients (mean age 32.3 years, female 47.8%) were included in the study. Uveitis was bilateral in 42.6% of cases. Anterior uveitis was the most common (39.2%) case, closely followed by intermediate uveitis (22.2%), posterior uveitis (22%), and panuveitis (16.4%). Specific diagnosis was established in 53.3% of patients. The three most common specific diagnoses were ocular tuberculosis (10.7%), followed by HLA-B27-related uveitis (10.1%) and Vogt-Koyanagi-Harada disease (VKHD; 8.4%). Ocular tuberculosis remained an important cause of uveitis in Bangladesh while HLA-B27 and VKHD were found to be the most common non-infectious uveitic entity.


Inhibition of anammox by sludge thermal hydrolysis and metagenomic insights.
Anaerobic ammonium oxidation (anammox) would be a feasible treatment method for thermal hydrolysis processed sidestream (THPS). Short-term study revealed that the 1/20 diluted THPS caused a 28% decrease of specific anammox activity. The MBR achieved a volumetric nitrogen loading rate of 3.64 kg/(m3·d) with undiluted regular sidestream (RS) fed, while the reactor crashed with 70% diluted THPS as feed. The ratio of produced NO3--N to consumed NH4+-N also decreased compared with RS feeding. Candidatus brocadia was the major anammox bacteria species with the average abundance of 33.3% (synthetic wastewater), 6.42% (RS) and 2.51% (THPS). The abundances of metagenome bins for dissimilatory nitrate reduction to ammonium (DNRA) increased in the system with THPS compared with RS. The reason for the inhibition of anammox by THPS could be the high content of organic carbon in THPS, which caused the over-population of heterotrophic bacteria, i.e. DNRA bacteria, leading to anammox bacteria washout.


A review on organophosphate esters: Physiochemical properties, applications, and toxicities as well as occurrence and human exposure in dust environment.
Organophosphate esters (OPEs) are widely used as flame retardants and plasticizers in the world. The use of OPEs has increased rapidly due to the prohibition of polybrominated diphenyl ethers. However, OPEs are mainly added to various materials by physical mixing, they are therefore easy to be released into the environment through volatilization, leaching, and abrasion during their production, use, transportation, and after disposal. Dust, as an important medium for human exposure to OPEs, has attracted extensive attention. Here, this article reviewed the current knowledge on the physiochemical properties, consumptions and applications, and ecotoxicities of OPEs, also synthesized the available data on the occurrence of 13 OPEs in outdoor and indoor dust environments around the world over the past decade. The results showed that the sum of OPEs (ΣOPEs) was the highest in outdoor dust from an e-waste disposal area in Tianjin of China (range: 1390-42700 ng/g dw; mean: 11500 ng/g dw). The highest ΣOPEs was found in Japan for home dust (range: 9300-11000000 ng/g dw; mean: 266543 ng/g dw), Sweden for office dust (range: 14000-1600000 ng/g dw; mean: 360100 ng/g dw) and daycare center dust (range: 40000-4600000 ng/g dw; mean: 1990800 ng/g dw), and Brazil for car dust (range: 108000-2050000 ng/g dw; mean: 541000 ng/g dw). The use pattern of OPEs differed in different regions and countries. The exposure and risk assessment based on the data of OPEs in home dust indicated that the average daily intakes of OPEs via dust ingestion for children and adults were lower than the corresponding reference doses; and that the current human exposure to OPEs through indoor dust ingestion were not likely to pose risks to human health. Finally, the review pointed out the gaps of current research and provided the directions for further study on OPEs in dust environment.


Photic- and pattern-induced seizures: expert consensus of the Epilepsy Foundation of America Working Group.
In August, 2004, the Epilepsy Foundation of America convened a workshop to begin to develop an expert consensus on photosensitive seizures. Literature and data were reviewed, and consensus was derived from discussion. A flash is a potential hazard if it has luminance >or=20 cd/m2, occurs at a frequency of >or=3 Hz, and occupies a solid visual angle of >or=0.006 steradians (approximately 10% of the central visual field or 25% of screen area at typical viewing distances). A transition to or from saturated red also is considered a risk. A pattern with the potential for provoking seizures contains clearly discernible stripes, numbering more than five light-dark pairs of stripes in any orientation. When the light-dark stripes of any pattern collectively subtend at the eye from the minimal-expected viewing distance a solid angle of >0.006 steradians, the luminance of the lightest stripe is >50 cd/m2, and the pattern is presented for >or=0.5 s, then the pattern should display no more than five light-dark pairs of stripes, if the stripes change direction, oscillate, flash, or reverse in contrast; if the pattern is unchanging or smoothly drifting in one direction, no more than eight stripes. These principles are easier to apply in the case of fixed media, for example, a prerecorded TV show, which can be analyzed frame-by-frame, as compared with interactive media. A consensus view of stimuli likely to provoke visually evoked seizures can be developed.


The efficacy of an ACLS training program for resuscitation from cardiac arrest in a rural community.
To determine whether an advanced cardiac life support (ACLS) course in a rural hospital will improve resuscitation success from cardiac arrest. A retrospective case review of all patients in cardiac arrest during a 13-month period before and after the institution of an ACLS training program. Emergency department of a 42-bed rural, community hospital in a community with no prehospital advanced life support or early defibrillation. All patients in cardiac arrest were entered into the data base. Twenty-nine patients were included in the pre-ACLS period and 35 in the post-ACLS period. There were no significant differences in age, gender, initial rhythm, comorbid diseases, witnessed versus unwitnessed arrest, or total arrest time in the patients in the pre-ACLS period compared with those in the post-ACLS period. ACLS provider training. Patients in cardiac arrest who had ventricular fibrillation/tachycardia as their initial rhythm had significant improvement in resuscitation success compared with patients in ventricular fibrillation/tachycardia in the pre-ACLS period (six of 15 versus none of nine, P < .05). Out-of-hospital cardiac arrest resuscitation was more successful in the post-ACLS period than in the pre-ACLS period (five of 30 versus none of 25, P < .05). Overall, seven of 35 patients (20%) were resuscitated successfully in the post-ACLS period, with two patients surviving to hospital discharge. This was not significantly different than the two of 29 patients (7%) resuscitated in the pre-ACLS period, with one patient surviving to discharge. The institution of an ACLS-provider course in a rural community hospital was associated with improvement in initial resuscitation for patients with ventricular fibrillation/tachycardia and out-of-hospital arrest.


Cystoid macular edema in gyrate atrophy of the choroid and retina: a fluorescein angiography and optical coherence tomography evaluation.
To analyze the importance f optical coherence tomography (OCT) to diagnose the cystoid macular edema in a case of gyrate atrophy. Observational case report. A 12-year-old boy presenting with gyrate atrophy of the choroid and retina underwent ophthalmologic, clinical, and laboratory tests. Plasma ornithine level was 735 mumol/l. Fluorescein angiography showed bilateral hyperfluorescence involving the central region of the macula. Optical coherence tomography (OCT) disclosed bilateral intraretinal cysts areas of low reflectivity with occasional high-signal elements bridging the retinal layers and intraretinal thickening. Both fluorescein angiography and OCT were helpful to confirm the diagnosis of macular involvement as a complication of gyrate atrophy of the choroid and retina in a patient who presented without any clinical evidence of cystoid macular edema, except a decrease in visual acuity.


Comparison of immunoglobulin and complement deposition in multiple biopsies from the uninvolved skin in dermatitis herpetiformis.
The distribution of immunoglobulins and C3 component of complement (C3) in the skin of twenty-four patients with dermatitis herpetiformis was studied. Skin biopsies were taken from three sites, the extensor surface of the elbow, the flexor surface of the forearm and from the thigh. Twenty-two (90%) patients showed variation in deposits of immunoglobulins and C3 at the three sites. IgA was present in all patients, but differed in quantities deposited at the three sites in nineteen (80%) patients. Similar variation between sites was observed with IgG, IgM and C3. There was variation within three biopsies, IgA being absent from some sections and present in others. Three patients had a continuous pattern of IgA deposition. One had both continuous and papillary deposits within a single section. There was no difference in the incidence or quantity of immunoglobulin and C3 between the elbow, forearm and thigh. There was observed to be a diminution in quantity of IgA and incidence of C3 in patients taking a gluten-free diet. Deposition of IgA, IgM, IgG and C3 is not uniform throughout the skin and conclusions drawn from the quantity of immunoglobulin and C3 in a single biopsy may not be reliable.


Production optimization and characterization of recombinant cutinases from Thermobifida fusca sp. NRRL B-8184.
Two genes, cut1 and cut2, of Thermobifida fusca NRRL B-8184 with cutin-hydrolyzing activity were cloned and expressed in Escherichia coli BL21 (DE3) separately. Enhanced expression was achieved after screening of six different media, optimization of the culture conditions and medium components. Among the screened media, modified Terrific Broth was found to be the best for maximum production of recombinant cutinases in E. coli BL21 (DE3). Under optimal conditions, the production of recombinant Cut1 and Cut2 (cutinases) were found to be 318±0.73 and 316±0.90 U/ml, respectively. The production of recombinant cutinases was increased by 11-fold as compared with T. fusca NRRL B-8184 wild-type strain. Both the recombinant cutinases were purified to homogeneity. They were found to be thermostable, organic solvent, and surfactant tolerant. Both the cutinase were active in a broad range of temperature (40-80 °C) and pH (6.8-9) with optimum activity at pH 8.0 and 55 °C.


Spermine Protects Cardiomyocytes from High Glucose-Induced Energy Disturbance by Targeting the CaSR-gp78-Ubiquitin Proteasome System.
To determine the mediation of spermine on energy metabolism disorder and diabetic cardiomyopathy (DCM) development as well as the underlying mechanisms. An in vitro model of DCM was established by incubating primary cultured neonatal rat cardiomyocytes with high glucose (HG). Spermine content was assessed by RP-HPLC. The protein levels were detected by western blot. Mitochondrial functions were analyzed using the respiratory chain complex assay kit and immunofluorescence staining. The endogenous content of spermine was decreased in the HG group, and the protein levels of ornithine decarboxylase, respiratory chain complex (I-V), mitochondrial fusion-related protein (Mfn1, Mfn2), Cx43, N-cadherin, CaSR, and β-catenin (in cytomembrane) were also down-regulated by HG. In contrast, the protein levels of spermine-N1-acetyltransferase, gp78, Fis1, Drp1, and β-catenin were up-regulated by HG. Meanwhile, we observed that HG increased ubiquitination levels of Mfn1, Mfn2, and Cx43, decreased membrane potential (ΔΨm), and the opening of mitochondrial permeability transport pore (mPTP) followed by intracellular ATP leakage. The supplement of spermine or siRNA-mediated knockdown of gp78 significantly alleviated the detrimental effects of HG, while downregulation of CaSR aggravated the development of DCM. We further confirmed that the lower level of spermine by HG activates the gp78-ubiquitin-proteasome pathway via downregulation of CaSR protein level, which in turn damages mitochondrial gap junction intercellular communication and leads to reduced ATP level. The protective role of spermine on energy metabolism disorder is based on higher CaSR protein level and lower gp78 activation, pointing to the possibility that spermine can be a target for the prevention and treatment of DCM.


Studies on steroids. CCXXVII. Separation and determination of bile acid 7- and 12-sulphates in urine by high-performance liquid chromatography with fluorescence labelling.
A method for the characterization and determination of bile acid 7- and 12-sulphates in urine without prior deconjugation is described. The sulphate fraction was obtained from an urine specimen by passing it through a Sep-Pak C18 cartridge, followed by group separation by ion-exchange chromatography on a lipophilic gel, piperidinohydroxypropyl Sephadex LH-20. Bile acid 7- and 12-sulphates were derivatized quantitatively into the fluorescent compounds through the hydroxyl group at C-3 by treatment with 1-anthroyl nitrile in the presence of quinuclidine in acetonitrile. Subsequent resolution into individual 7- and 12-sulphates was attained by high-performance liquid chromatography (HPLC) on a Cosmosil 5C18 column using 0.3% potassium phosphate buffer (pH 4.0)-methanol (1:3) as a mobile phase. The 3-(1-anthroyl) derivatives of 7- and 12-sulphates were monitored by fluorescence detection. Taurochenodeoxycholate 7-sulphate in human urine was unequivocally identified on the basis of behaviour in HPLC using mobile phases of different pH values. The present method has proved to be applicable to the characterization and quantification of bile acid 7- and 12-sulphates in human urine.


Addition of zeolite and superphosphate to windrow composting of chicken manure improves fertilizer efficiency and reduces greenhouse gas emission.
This study investigated the impact of adding zeolite (F), superphosphate (G), and ferrous sulfate (L) in various combinations on reducing greenhouse gas (GHG) emission and improving nitrogen conservation during factory-scale chicken manure composting, aimed to identify the combination that optimizes the performance of the process. Chicken manure was mixed with F, G, FL, or FGL and subjected to windrow composting for 46 days. Results showed that global warming potential (GWP) was reduced by 21.9% (F), 22.8% (FL), 36.1% (G), and 39.3% (FGL). Further, the nitrogen content in the final composting product increased by 27.25%, 9.45%, and 21.86% in G, FL, and FGL amendments, respectively. The fertilizer efficiency of the compost product was assessed by measuring the biomass of plants grown in it, and it was consistent with the nitrogen content. N2O emission was negligible during composting, and 98% of the released GHGs comprised CO2 and CH4. Reduction in GHG emission was mainly achieved by reducing CH4 emission. The addition of FL, G, and FGL caused a clear shift in the abundance of dominant methanogens; particularly, the abundance of Methanobrevibacter decreased and that of Methanobacterium and Methanocella increased, which was correlated with CH4 emissions. Meanwhile, the changes in moisture content, NH4+-N content, and pH level also played an important role in the reduction of GHG emission. Based on the effects of nitrogen conservation, fertilizer efficiency improvement, and GHG emission reduction, we conclude that G and FGL are more beneficial than F or FL and suggest these additives for efficient chicken manure composting.


Cloning and generation of a genetic map of bacteriophage N4 DNA.
Analysis of coliphage N4 development has been hindered by the lack of a genetic map. Conventional methods of complementation and recombination have been inadequate because N4 shows very high levels of recombination, which are independent of the host recombination system. We have cloned restriction fragments of the 72-kb genome of N4 and have used these clones to rescue a collection of suppressor-sensitive and temperature-sensitive mutants. After mutations were localized to a small region by marker rescue, complementation groups were defined. In this way several functions essential for transcription and replication have been mapped. Finally, a nonessential 6-kb region of the N4 genome has been identified by characterizing phage deletions isolated after heat and citrate treatment of virions.


Sphingolipids in human lens membranes: an update on their composition and possible biological implications.
The unique nature of the most abundant phospholipids in human lens membranes remained overlooked until the 1990s when it was possible to discern dihydrosphingomyelins (DHSMs) from the more common sphingomyelins (SMs). Unlike in other mammalian membranes, DHSMs comprise nearly half of the phospholipids in adult human lenses. Compared to SMs with a trans double bond between carbons 4 and 5 of the sphingoid backbone, the absence of this unsaturation site in DHSMs allows the participation of the OH group on C3 in intermolecular H-bonds and leads to stronger interlipid interactions with both neighboring DHSMs and cholesterol. Phospholipid compositional changes with age and lens region observed in mammals with various life spans and lens growth rates, suggest that the highest levels of DHSMs along with the lowest amounts of phosphatidylcholines and SMs are found in lenses with the lowest growth rate, namely human lenses. The participation of phospholipid metabolites in the control of mitosis and elongation of lens cells is plausible and deserves investigation.


Helicobacter pylori strain ATCC700392 encodes a methyl-accepting chemotaxis receptor protein (MCP) for arginine and sodium bicarbonate.
Helicobacter pylori ATCC43504 responds chemotactically to aspartic acid and serine, but not to arginine, nor to sodium bicarbonate. In contrast, H. pylori ATCC700392 (strain 26695) shows chemotaxis to all four attractants. Open reading frame HP0099 from H. pylori 26695 is predicted to encode one of three methyl-accepting chemotaxis receptor proteins (MCPs). When Escherichia coli is transformed with a plasmid carrying HP0099 from strain 26695, the recombinants acquire chemotaxis to arginine, bicarbonate, and urea. In H. pylori 43504, the HP0099 gene is interrupted with a mini-IS605 insertion, which accounts for its inability to recognize arginine and bicarbonate as attractants. Together, these results argue that the H. pylori HP0099 gene encodes an MCP for arginine and bicarbonate.


Therapeutic arthroscopy of the knee.
This paper describes transcutaneous therapeutic procedures performed during arthroscopy. Sixty-six patients were treated. Small loose bodies were flushed out through the arthroscope in 7 cases. In 19 of 24 knees a loose body 0.5-2 cm in size was extracted either with a Dormia stone-dislodger or a pituitary rongeur. In 5 patients we failed to remove the loose body transcutaneously and arthrotomy was performed. A meniscus was resected in 17 patients using a pituitary rongeur alone or in combination with some other instrument. The late result was good in 14, but 3 subsequently underwent arthrotomy. Various procedures such as lateral release of the patella by a special technique, removal of intra-articular sutures and other measures were also undertaken. No complications occurred and the duration of sick leave was usually short. Before arthrotomy for removal of loose bodies or resection of ruptured menisci is performed, we feel that an attempt at transcutaneous therapy under arthroscopy should be made.


An overview on human serum lectins.
An extensive literature survey done on the various naturally occurring lectins in human serum upon its salient features such as methods of detection, level and sites of synthesis, binding specificity, cation dependency, modes of isolation, molecular and functional characterization way back from 1930s to till date was presented in a tabulated section. In addition, the generation of lectin and other immune molecules in vertebrates upon treatment with exogenous elicitors has also been framed in a tabular form. Furthermore, ANEW lectin induced in human serum for the very first time by an exogenous elicitor was detected, isolated and characterized by us whose features are also tabulated explicitly.