The Aeromonas caviae AHA0618 gene modulates cell length and influences swimming and swarming motility.
Aeromonas caviae is motile via a polar flagellum in liquid culture, with a lateral flagella system used for swarming on solid surfaces. The polar flagellum also has a role in cellular adherence and biofilm formation. The two subunits of the polar flagellum, FlaA and FlaB, are posttranslationally modified by O-linked glycosylation with pseudaminic acid on 6-8 serine and threonine residues within the central region of these proteins. This modification is essential for the formation of the flagellum. Aeromonas caviae possesses the simplest set of genes required for bacterial glycosylation currently known, with the putative glycosyltransferase, Maf1, being described recently. Here, we investigated the role of the AHA0618 gene, which shares homology (37% at the amino acid level) with the central region of a putative deglycosylation enzyme (HP0518) from the human pathogen Helicobacter pylori, which also glycosylates its flagellin and is proposed to be part of a flagellin deglycosylation pathway. Phenotypic analysis of an AHA0618 A. caviae mutant revealed increased swimming and swarming motility compared to the wild-type strain but without any detectable effects on the glycosylation status of the polar flagellins when analyzed by western blot analysis or mass spectroscopy. Bioinformatic analysis of the protein AHA0618, demonstrated homology to a family of l,d-transpeptidases involved in cell wall biology and peptidoglycan cross-linking (YkuD-like). Scanning electron microscopy (SEM) and fluorescence microscopy analysis of the wild-type and AHA0618-mutant A. caviae strains revealed the mutant to be subtly but significantly shorter than wild-type cells; a phenomenon that could be recovered when either AHA0618 or H. pylori HP0518 were introduced. We can therefore conclude that AHA0618 does not affect A. caviae behavior by altering polar flagellin glycosylation levels but is likely to have a role in peptidoglycan processing at the bacterial cell wall, consequently altering cell length and hence influencing motility.


[Role of secondary lymphoid tissue chemokine in the pathogenesis of rat ulcerative colitis].
To investigate the effect of secondary lymphoid tissue chemokine (SLC) on experimental colon lesions in rats with ulcerative colitis. Sixty Sprague-Dawley rats were randomly divided into control group, model group and SLC intervention group. Colonic mucosal lesions of different groups were observed with HE staining for inflammation and lymphocyte homing situation. Cytokine IL-2 and IL-6 levels were measured by ABC-ELISA. Semi-quantitative RT-PCR was used to examine the colonic SLC expression. Intestinal inflammation score and colonic cytokine levels were significantly different among three groups (P<0.05, P<0.01). Abnormal lymphocyte homing phenomenon under colonic mucosa was found in the model group and the intervention group. SLC mRNA expression of the model and intervention groups increased significantly compared with the control group (0.846+/-0.047, 0.768+/-0.135 vs 0.312+/-0.112, P<0.01). However, there was no significant difference between model group and intervention group. SLC may play an important role in experimental colonic mucosal inflammation in rats with ulcerative colitis. Blockade of SLC may be one of effective ways in reducing colonic mucosal inflammation.


Human C3b- and C4b-regulatory proteins: a new multi-gene family.
The complement cascade is regulated to prevent inappropriate activation. This regulation is targeted not only at the initiation of the cascade but also at the amplification andjunctional (C3) steps. Five glycoproteins with both complement regulatory activity and binding affinity for C3b/C4b have been characterized. In plasma these molecules are factor H(H) and C4-binding protein (C4-bp) and, on cells, they are the C3b/C4b receptor (CR1), decay-accelerating factor (DAF), and gp45-70. Here Michael Holers and his colleagues review structural, functional and genetic studies of these proteins and discuss the evidence for a new multi-gene family with a common ancestral protein.


Comparative characterization of the HGF/Met and MSP/Ron systems in primary pancreatic adenocarcinoma.
Pancreatic cancer is an aggressive disease with a poor prognosis for which current standard chemotherapeutic treatments offer little survival benefit. Receptor tyrosine kinases (RTK)s have garnered interest as therapeutic targets to augment or replace standard chemotherapeutic treatments because of their ability to promote cell growth, migration, and survival in various cancers. Met and Ron, which are homologous RTKs activated by the ligands hepatocyte growth factor (HGF) and macrophage stimulating protein (MSP), respectively, are over-activated and display synergistic malignant effects in several cancers. Despite the homology between Met and Ron, studies that have directly compared the functional outcomes of these systems in any context are limited. To address this, we sought to determine if the HGF/Met and MSP/Ron systems produce overlapping or divergent contributions towards a malignant phenotype by performing a characterization of MSP and HGF driven signaling, behavioral, and transcriptomic responses in a primary pancreatic adenocarcinoma (PAAD) cell line in vitro. The impact of dual Met and Ron expression signatures on the overall survival of PAAD patients was also assessed. We found HGF and MSP both encouraged PAAD cell migration, but only HGF increased proliferation. RNA sequencing revealed that the transcriptomic effects of MSP mimicked a narrow subset of the responses induced by HGF. Analysis of clinical data indicated that the strong prognostic value of Met expression in primary PAAD does not appear to be modulated by Ron expression. The relatively reduced magnitude of MSP-dependent effects on primary PAAD cells are consistent with the limited prognostic value of Ron expression in this cancer when compared to Met. Although HGF and MSP produced a differing breadth of responses in vitro, overlapping pro-cancer signaling, behavioral, and transcriptional effects still point to a potential role for the MSP/Ron system in pancreatic cancer.


Presence of selected metabolic syndrome components in patients with psoriasis vulgaris.
Recent studies have suggested a strong association between psoriasis and obesity, dyslipidemia, hypertension, resistance to insulin and metabolic syndrome. To assess the prevalence of selected metabolic syndrome components in patients with psoriasis and the effect of the abnormalities on the disease activity. Two hundred and forty-six patients diagnosed with psoriasis and 75 healthy individuals as controls were included in the study. Psoriasis activity was evaluated by the Psoriasis Area and Severity Index (PASI). There was a statistically significant difference in triglyceride concentration between psoriasis patients and controls (p = 0.00001), which was not found for high-density lipoprotein (HDL) concentration. Mean values of serum glucose level in patients with psoriasis were significantly higher than in controls (p = 0.046). Further statistical analysis of the obtained results showed significantly higher systolic blood pressure in the psoriasis patients than in the controls (p = 0.0001), but there was no statistically significant difference in diastolic blood pressure between the investigated groups (p > 0.05). Higher prevalence of metabolic syndrome components was observed in patients with psoriasis than in the general population.


Genome-Wide Analysis and Expression Profiling of the Glutathione Peroxidase-like Enzyme Gene Family in Solanum tuberosum.
Glutathione peroxidase-like enzyme is an important enzymatic antioxidant in plants. It is involved in scavenging reactive oxygen species, which can effectively prevent oxidative damage and improve resistance. GPXL has been studied in many plants but has not been reported in potatoes, the world's fourth-largest food crop. This study identified eight StGPXL genes in potatoes for the first time through genome-wide bioinformatics analysis and further studied the expression patterns of these genes using qRT-PCR. The results showed that the expression of StGPXL1 was significantly upregulated under high-temperature stress, indicating its involvement in potato defense against high-temperature stress, while the expression levels of StGPXL4 and StGPXL5 were significantly downregulated. The expression of StGPXL1, StGPXL2, StGPXL3, and StGPXL6 was significantly upregulated under drought stress, indicating their involvement in potato defense against drought stress. After MeJA hormone treatment, the expression level of StGPXL6 was significantly upregulated, indicating its involvement in the chemical defense mechanism of potatoes. The expression of all StGPXL genes is inhibited under biotic stress, which indicates that GPXL is a multifunctional gene family, which may endow plants with resistance to various stresses. This study will help deepen the understanding of the function of the potato GPXL gene family, provide comprehensive information for the further analysis of the molecular function of the potato GPXL gene family as well as a theoretical basis for potato molecular breeding.


Granulocyte colony-stimulating factor administration for infertile women with thin endometrium in frozen embryo transfer program.
We aimed to evaluate the effectiveness of granulocyte colony-stimulating factor (G-CSF) administration for infertile women with thin endometrium in frozen embryo transfer program. Among 59 infertile patients with thin endometrium (≤7 mm), 34 patients received uterine infusion of recombinant human G-CSF (100 μg/0.6 mL) on the day of ovulation or administration of progesterone or human chorionic gonadotropin, with 40 cycles defined as G-CSF group and 49 previous cycles as self-controlled group, and 25 patients refused, with 80 cycles defined as the control group. Higher proportion of induced cycles and lower proportion of natural cycles were observed in the G-CSF group, when compared to the self-controlled group or control group (P < .05). The cycle cancellation rate was, in descending order, 69.39% in self-controlled group, 48.75% in control group, and 17.50% in G-CSF group, with significant difference (P < .05). The implantation rate and clinical pregnancy rate per embryo transfer were similar in all the groups (P > .05). Our study fails to demonstrate that G-CSF has the potential to improve embryo implantation and clinical pregnancy rate of the infertile women with thin endometrium.


Effect of one-stop hybrid coronary revascularization on postoperative renal function and bleeding: a comparison study with off-pump coronary artery bypass grafting surgery.
Although 1-stop hybrid coronary revascularization offers potential benefits for selected patients with multivessel coronary artery disease, the exposure to contrast dye and potent antiplatelet drugs could increase the risk of postoperative acute kidney injury and coagulopathy. The goal of the present study was to compare the measures of renal function, postoperative bleeding, and transfusion requirements in patients undergoing hybrid revascularization compared with off-pump coronary artery bypass grafting (CABG). We retrospectively analyzed the data from 141 consecutive patients who had undergone 1-stop hybrid coronary revascularization from June 2007 to January 2011. Propensity score matching with 141 off-pump CABG patients from our surgical database was performed for comparison. The change in renal function, cumulative chest tube drainage, and clinical outcome parameters were compared between the 2 groups. Compared with off-pump CABG, patients undergoing hybrid revascularization had significantly less chest tube drainage at 12 hours after surgery (P = .04) and for the total amount during the postoperative period (P < .001) and required fewer blood transfusions (P = .001). The hybrid group had a higher incidence of acute kidney injury, but this did not reach statistical significance (25.2% vs 17.6%, P = .13). The hybrid group required less inotropic and vasoactive support, had fewer respiratory complications, required a shorter time of mechanical support, and had a decreased length of intensive care unit stay. Compared with off-pump CABG, 1-stop hybrid coronary revascularization was associated with benefits such as less postoperative bleeding and blood transfusion requirements without significantly increasing the additional risk of acute kidney injury.


[Hybrid surgery for complex symptomatic intracranial fistulas: a technical note].
Objective: To explore the efficacy of hybrid management of complex symptomatic intracranial fistulas in neurovascular hybrid operating room. Methods: From March 2014 to January 2015, 2 complex dural arteriovenous fistulas and 1 carotid cavernous fistulas were managed by hybrid surgeries in the PLA Rocket Force General Hospital.With first attempts with endovascular treatment failed, all cases were finally managed by hybrid surgery.Dural arteriovenous fistulas were approached via meningeal artery followed craniotomy.The carotid cavernous fistulas were treated by direct puncture into the left cavernous sinus after craniotomy. Results: Post-operative angiography demonstrated complete occlusion for 2 cases and nearly complete occlusion for 1 case.All 3 cases had no complications.On discharge 2 patients presented no symptoms and 1 greatly improved.Within the follow-up (1-33 months), 1 patient had recurrence after 21 months and received re-embolization with complete occlusion. Conclusion: Hybrid surgery is a promising method to manage complex intracranial fistulas.


Thymoma: a clinicopathologic study based on the new World Health Organization classification.
This study explored the relationship between the histologic subtype of thymoma according to the new World Health Organization histologic classification and the clinical findings, as well as the prognostic significance of the classification. A total of 130 patients with thymoma, who underwent resection at the National Cancer Center Hospital, Tokyo, from 1962 to 2000, were studied retrospectively. The histologic subtype of thymoma was determined according to the new World Health Organization histologic classification. The stage was also determined according to a modified Masaoka's classification as stage I, II, III, IVa, or IVb. To determine the factors that may affect the prognosis of thymoma, a multivariate analysis with Cox's proportional hazards regression model was performed. The distribution of histologic subtype was type A (n = 18), type AB (n = 56), type B1 (n = 15), type B2 (n = 29), and type B3 (n = 12). A close correlation was seen between the histologic subtype and stage (P =.000). The overall survivals at 5 and 10 years were 92% and 91%, respectively. The 5- and 10-year survivals according to stage were 100% and 100% (stage I, n = 40; stage II, n = 54), 81% and 76% (stage III, n = 25), and 47% and 47% (stage IV, n = 11), respectively. The difference in survival between stage III and stage IV was significant (P =.000). Patients with type A or AB thymoma demonstrated a 100% survival at both 5 and 10 years. Recurrences were seen in 12 patients with complete resection. According to a multivariate analysis, tumor size (P =.001), completeness of resection (P =.002), histologic subtype (P =.011), and stage (P =.00) were significant prognostic factors. The World Health Organization histologic classification significantly correlated with the clinical stage. Tumor size, completeness of resection, histologic subtype, and stage predicted the prognosis of thymoma.


The immunohistochemical expression of E-cadherin in gastric cancer; correlations with clinicopathological factors and patients' survival.
The aim of our study is to investigate the immunohistochemical expression of E-cadherin in gastric carcinomas and in surrounding mucosa (normal or with lesions of chronic atrophic gastritis, intestinal metaplasia or dysplasia). We included 61 patients with gastric cancers operated in Emergency County Hospital Timisoara. We analyzed the E-cadherin immunohistochemical expression, the correlation with clinical and pathological factors and the outcome of the patients. The positive homogeneous pattern of staining for the cellular membranes is considered normal. The negative homogeneous or the heterogeneous pattern (of the cytoplasm and membrane) represented aberrant E-cadherin expression. Areas of chronic atrophic gastritis and intestinal metaplasia presented a normal pattern of immunostaining for the membranes. Aberrant E-cadherin expression was noticed in 30 cases of gastric carcinomas (49.2%) and in 11 cases (35.5%) of epithelial dysplasia in the surrounding tissue. Our results showed no correlation between E-cadherin expression and gender, age, tumor location, pT, pN, pTNM and lympho-vascular invasion. Aberrant E-cadherin immunostainings were significantly more frequent in diffuse-type carcinomas in comparison with the intestinal-type carcinomas (82.4% vs. 31.6%) (p = 0.000491 ES). Signet-ring carcinomas and anaplastic carcinomas presented a high-proportion of aberrant immunostainings (82.4% and 100%), as well as poor differentiated carcinomas (61.5%). Carcinomas with distant metastasis presented significantly more aberrant immunostainings than those without metastasis (71.4% vs. 42.6%). Five-year survival rate was significantly lower in patients with aberrant E-cadherin expression in comparison with the patients presenting normal staining (10% vs. 22.6%). In gastric carcinomas and areas of epithelial dysplasia, aberrant E-cadherin expression was significantly more frequent in comparison with the surrounding normal mucosa (p<0.001 ES). Our data suggest a strong correlation between Lauren's classification of gastric carcinomas and E-cadherin immunohistochemical expression. Assessment of the survival curve of the patients highlighted the role of prognostic factor for the aberrant immunohistochemical E-cadherin expression.


Comparison of microleakage under orthodontic brackets bonded with five different adhesive systems: in vitro study.
Orthodontic treatment is associated with numerous adverse side effects, such as enamel discoloration, demineralization or even caries. The presence of microleakage between the enamel and the adhesive and between the adhesive and the base of the orthodontic bracket allows penetration of the bacteria, molecules, and liquids into the enamel and can lead to unpleasant "white spot lesions" or secondary caries beneath and around the brackets. The aim of this in vitro study was to evaluate microleakage in five adhesive systems commonly used in orthodontic practice for bonding brackets. One hundred extracted premolars were divided into five groups of twenty teeth. Stainless steel Legend medium metal brackets were bonded to teeth using five adhesive systems: resin-reinforced glass ionomer cement GC Fuji Ortho LC (GCF) and composite materials Light Bond (LB), Transbond XT (TB), Trulock™ Light Activated Adhesive (TL), and GC Ortho Connect (GCO). The specimens were subjected to thermal cycling, stained with 2% methylene blue, sectioned with low-speed diamond saw Isomet and evaluated under a digital microscope. Microleakage was detected at the enamel-adhesive and adhesive-bracket interfaces from occlusal and gingival margins. Statistical analysis was performed using generalized linear mixed models with beta error distribution. Microleakage was observed in all materials, with GCF showing the highest amount of microleakage. Composite materials GCO, TB, and LB exhibited the lowest amount of microleakage with no statistical difference between them, while TL showed a statistically significantly higher amount of microleakage (p < 0.001). The enamel-adhesive interface had more microleakage in all composite materials (GCO, LB, TB, and TL) than the adhesive bracket-interface (p < 0.001). The highest amount of microleakage occurred in the gingival region in all materials. Composite materials showed better adhesive properties than a resin-reinforced glass ionomer cement. The presence of microleakage at the enamel-adhesive interface facilitates the penetration of various substances into enamel surfaces, causing enamel demineralization and the development of dental caries.


Role of central beta-adrenoceptors on stress-induced prolactin release in rats.
Adult Wistar male rats underwent immobilization stress (IS) during forty minutes. PRL secretion presented a remarkable increase after 5 minutes, and it was higher than pre-stress values during the entire duration of the experiment. The blockade of beta-1 adrenoceptors by icv injections of practolol did not modify IS-induced PRL release. IPS 339, a selective antagonist of beta-2 adrenoceptors, also injected icv, reduced PRL secretion during stress in a dose dependent fashion. The blockade of PRL secretion due to IPS 339 was reverted by a previous icv administration of salbutamol, a classical beta-2 agonist. The data presented here suggest that central beta-2 adrenoceptors activation is an important step in the control of stress-induced PRL secretion.


Quantitative phosphoproteomics to characterize signaling networks.
Reversible protein phosphorylation is involved in the regulation of most, if not all, major cellular processes via dynamic signal transduction pathways. During the last decade quantitative phosphoproteomics have evolved from a highly specialized area to a powerful and versatile platform for analyzing protein phosphorylation at a system-wide scale and has become the intuitive strategy for comprehensive characterization of signaling networks. Contemporary phosphoproteomics use highly optimized procedures for sample preparation, mass spectrometry and data analysis algorithms to identify and quantify thousands of phosphorylations, thus providing extensive overviews of the cellular signaling networks. As a result of these developments quantitative phosphoproteomics have been applied to study processes as diverse as immunology, stem cell biology and DNA damage. Here we review the developments in phosphoproteomics technology that have facilitated the application of phosphoproteomics to signaling networks and introduce examples of recent system-wide applications of quantitative phosphoproteomics. Despite the great advances in phosphoproteomics technology there are still several outstanding issues and we provide here our outlook on the current limitations and challenges in the field.


A thoracoscopically resected case of mediastinal parathyroid cyst.
A 67-year-old male visited his physician because of a 2-month history of cough and sputum. An abnormal shadow at the left upper mediastinum on chest x-ray film was detected, and the patient was referred to our department for further examination. Chest x-ray film revealed a round shadow at the left upper posterior mediastinum. Computed tomography(CT)revealed a uniform iso density mass about 4 cm in diameter, with a well-defined border. After the intravenous contrast administration, a slight peripheral enhancement was seen around the mass. On magnetic resonance imaging, the mass was hypointense in T1-weighting and hyperintense in T2-weighting. The contrast pattern was the same as that observed in the CT scan. On sagittal and coronal sections, the mass was adjacent to the aortic arch. Although a benign tumor was mostly suspected based on imaging findings, a malignant tumor was also possible. Accordingly, we resected this mass with video-assisted thoracoscopy. Findings at operation were a cystic mass. The pathological findings were compatible with benign parathyroid cyst, which was suspected to be the cystic degeneration of a parathyroid adenoma.


Disposition of xenobiotics: species differences.
Species differences are a major obstacle in predicting toxicity of xenobiotics from one species to another. Species differences in toxicity of drugs and other chemicals may be due to differences in pharmacokinetics or pharmacodynamics. This paper illustrates the point that species differences in pharmacokinetics of xenobiotics may be the result of differences in any of the processes contributing to the disposition of a xenobiotic. This is an important point because biotransformation as a cause of species differences for the disposition of xenobiotics has been overemphasized in the past, whereas only scant attention has been paid to the other 3 major contributing processes to disposition, viz. absorption, distribution, and excretion. This brief overview presents a balanced examination of all 4 major processes (absorption, distribution, biotransformation and excretion) as they affect the pharmacokinetics of xenobiotics in various species.


First Report of Rose Apple Leaf Spot Caused by Colletotrichum siamense in Thailand.
The rose apple (Syzygium samarangense (Blume) Merr. & L.M.Perry) plant has been commonly cultivated in Thailand. In May of 2022, leaf spot disease of rose apple was discovered in Chiang Mai Province, Thailand, with approximately 30% disease incidence. The typical symptoms initially showed brown spots (0.1 to 0.5 mm in diameter) with a yellow halo surrounding. These spots then expanded with black edges and the infected leaves appear blighted and desiccated. In humid conditions, pale yellow conidiomata formed on the lesions. Small pieces (5 × 5 mm2) of the margins between lesions and the healthy tissue were surface disinfected with 1% NaClO for 1 min, 70% ethanol for 30 s, and washed three times with sterile distilled water. Tissues were placed on potato dextrose agar (PDA) and incubated at 25 ºC for three days. Three fungal isolates (SDBR-CMU419, SDBR-CMU420, and SDBR-CMU421) were obtained that exhibited similar morphology. Fungal colonies appeared white to gray with cottony mycelia after incubation on PDA at 25 ºC for one week. All fungal isolates produced asexual morph on PDA. Setae were 5590 × 2.53.5 µm, brown with 13-septa, cylindrical base, and tip rounded. Conidiophores were hyaline to pale brown, septate, and branched. Conidiogenous cells were hyaline to pale brown, cylindrical to ampulliform, 2050 µm long (n = 50). Conidia were one-celled, hyaline, smooth-walled, aseptate, straight, cylindrical, end round, guttulate, 1017 × 35 µm (n = 50). Appressoria were mostly formed from mycelia, oval to irregular, brown to dark brown, smooth-walled, 610 × 57 µm (n = 50). Morphologically, all fungal isolates resembled to Colletotrichum (Weir et al. 2012; Jayawardena et al. 2021). The internal transcribed spacer (ITS) region of the ribosomal DNA, actin (act), β-tubulin (tub2), calmodulin (CAL), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were amplified using primer pairs ITS5/ITS4 (White et al. 1990), ACT-512F/ACT-783R (Carbone and Kohn 1999), T1/T22 (O'Donnell and Cigelnik 1997), CL1C/CL2C (Weir et al. 2012), and GDF1/GDR1 (Templeton et al. 1992), respectively. The ITS (ON740892 to ON740894), act (ON759242 to ON759244), tub2 (ON759245 to ON759247), CAL (ON759248 to ON759250), and GAPDH (ON759251 to ON759253) sequences were deposited in GenBank. Multi-gene (combined data set of ITS, GAPDH, CAL, act, and tub2) maximum phylogenetic analyses indicated that all fungal isolates clustered with C. siamense ICMP 18578 (type strain) with strong statistical (99% ML) support. For pathogenicity test, asymptomatic leaves, stems and fruits detached from healthy plants were surface disinfected using 0.1% NaClO for 3 min, washed three times with sterile distilled water, and air-dried. A uniform wound (3 pores, 1 mm in width) was made at the equator of each leaf, stem and fruit using aseptic needles. Mycelial plugs (5 mm in diameter) and conidia suspensions (1 × 106 conidia/ml) of each fungal isolate grown on PDA at 25 ºC for one week were used to inoculate both wounded and unwounded samples by the detached method (Huda‑Shakirah et al. 2022; Suwannarach et al. 2022). Plugs of PDA and sterile distilled water were used as controls. Ten replications were performed for each treatment and the experiment was repeated twice. All inoculated samples were incubated in a moist chamber at 25 ºC with 90% relative humidity. The disease severity index was used to evaluate the specimens (Acar et al. 2008; Ngegba et al. 2017). After one week, both wounded and unwounded leaves that inoculated with mycelial plugs and conidia suspensions showed brown leaf spots and a weak infection. Mycelial plugs inoculated on both wounded and unwounded fruits revealed a moderate infection, but inoculation of conidia suspensions showed a weak infection. No symptoms of disease were observed on the inoculated stems. Control leaves, stems and fruits remained asymptomatic. The pathogen C. siamense was re-isolated from spot and rot lesions on PDA in order to fulfill Koch's postulates. Phoulivong et al. (2012) reported that C. siamense is a causal agent of fruit rot in rose apples cultivated in Lao and Thailand. To our knowledge, this is the first report of C. siamense causing leaf spots on rose apple plants in Thailand. Importantly, these findings will provide crucial information for epidemiologic studies and in the development of appropriate management strategies for this newly emerging disease.


[Results of treatment of congenital hip dislocation by extensionrepositioning and Hanausek-retention].
In the past 4 years all our patients below the age of three years, suffering from luxation or dysplasia of the hipjoint, were treated only conservatively. For repositioning we used a modified overhead-extension (Extensionsreposition). The "Hanausek-Apparat" was used only for retention. By this method all luxations could be reponed. Because of the low rate of re-dislocations and femur-head-nekroses, which decreased significantly from 23 per cent to 3.9 per cent, our method proved to be superior to manual repositioning under general anaesthesia, plaster-extension or early operation.


It is time to revisit current dietary recommendations for saturated fat.
The extent to which a high intake of saturated fat (SFA) increases the risk of cardiovascular disease (CVD) has become a highly controversial topic. Dietary SFA primarily raises low-density lipoprotein cholesterol, while having a relatively neutral impact on other key CVD risk factors. Recent epidemiological data also challenge the concept that SFA increases the risk of CVD. This short review provides arguments for the urgency to re-assess the association between dietary SFA and CVD risk in light of recent data on the subject.


Selective elimination of the delayed-type hypersensitivity response by extracorporeal thoracic duct filtration.
Calves were sensitized to tuberculin and histoplasmin. The delayed-type hypersensitivity skin response to these antigens was produced and the diameter of induration measured. Repeated skin tests prior to filtration demonstrated that the amount of induration produced by these skin tests was closely reproducible. Histoplasmin or tuberculin-coated columns were then introduced into a closed circuit extracorporeal thoracic duct circulation. A significant (P is less than 0.01) reduction or ablation of the delayed-type hypersensitivity response was obtained to the antigen used to coat the column. In contrast, no significant reduction occurred in the skin test response to the other antigen. Repeated skin tests to both antigens after the cessation of filtration showed a gradual rise toward prefiltration levels in the skin test to the filtered antigen. The results of these experiments indicate that a selective population of T lymphocytes can be removed from an in vivo system. The removal of these cells can selectively reduce a delayed-type hypersensitivity skin test response to a particular antigen. These results are consistent with the hypothesis that a type of in vivo selective immunosuppression can be produced by antigen-coated columns when they are placed in an extracorporeal thoracic duct lymph circulation system.


Dynamic studies with radionuclides.
Scintigraphy, the visual display of radioactivity, shows the size, shape and structure of the organ being studied. This information should be complemented with dynamic studies which will indicate the distribution of the radioactivity in the organ in relation to time. Dynamic studies must be performed with external detectors and the gamma camera. Circulation (systemic, pulmonary or cerebrospinal fluid) can be studied depending on the method of administration and the radionuclide used. The indicators are the same as for arteriography. Regional distribution of ventilation can be studied using radioactive gases. Regional distribution of ventilation of the lungs and mucociliary clearance can also be studied using inhaled particles. Dynamic studies do not replace but only supplement scintigraphy. They should be quantitated to obtain objective information.


Saccharomyces cerevisiae cells with defective spindle pole body outer plaques accomplish nuclear migration via half-bridge-organized microtubules.
Cnm67p, a novel yeast protein, localizes to the microtubule organizing center, the spindle pole body (SPB). Deletion of CNM67 (YNL225c) frequently results in spindle misorientation and impaired nuclear migration, leading to the generation of bi- and multinucleated cells (40%). Electron microscopy indicated that CNM67 is required for proper formation of the SPB outer plaque, a structure that nucleates cytoplasmic (astral) microtubules. Interestingly, cytoplasmic microtubules that are essential for spindle orientation and nuclear migration are still present in cnm67Delta1 cells that lack a detectable outer plaque. These microtubules are attached to the SPB half- bridge throughout the cell cycle. This interaction presumably allows for low-efficiency nuclear migration and thus provides a rescue mechanism in the absence of a functional outer plaque. Although CNM67 is not strictly required for mitosis, it is essential for sporulation. Time-lapse microscopy of cnm67Delta1 cells with green fluorescent protein (GFP)-labeled nuclei indicated that CNM67 is dispensable for nuclear migration (congression) and nuclear fusion during conjugation. This is in agreement with previous data, indicating that cytoplasmic microtubules are organized by the half-bridge during mating.


Dynamic induction of enantiomeric excess from a prochiral azobenzene dimer under circularly polarized light.
The ability to photoinduce enantiomeric excess from the chirality of circularly polarized light (CPL) is pertinent to the study of the origin of homochirality in biomolecules. Such CPL-induced reactions, including both chirality generation and formation of partial enantiomeric imbalance, from nonchiral starting compounds have been known, however, only for the conversion of diarylolefins into chiral helicenes. In this study we synthesized three different prochiral molecules, each featuring a pair of photoisomerizable phenylazo moieties arranged symmetrically upon the phenyl rings of an sp3-hybridized carbon atom (1), the phenyl rings of [2.2]paracyclophane (2), and the ortho positions of a phenyl ring bearing a naphthyl unit (3), and then investigated the possibility of photoinducing enantiomeric excess under CPL. Irradiation of 1-3 with light induced E ↔ Z photoisomerizations of their azobenzene moieties, giving mixtures of their EE, EZ, and ZZ isomers in the photostationary state (PSS). Among these regioisomers, the EZ forms are chiral and existed as racemic mixtures of R and S stereoisomers. Upon CPL irradiation of 3, circular dichroism (CD) revealed enantiomeric enrichment of one of the EZ stereoisomers; furthermore, irradiation with r- or l-CPL gave CD signals opposite in sign, but with equal intensity, in the PSS. In contrast, 1 and 2 did not give any detectable induced CD upon CPL irradiation. These experimental results can be explained by considering the different Kuhn anisotropy factors (g) of the (R)-EZ and (S)-EZ stereoisomers of 1-3, assuming that the origin of the enantiomeric excess is the enantio-differentiating photoisomerization from EZ stereoisomers to nonchiral EE or ZZ regioisomers by r- or l-CPL. In short, we demonstrate the simultaneous induction of chirality and enantiomeric excess from a prochiral azobenzene dimer via a chiral regioisomer formed in situ upon CPL irradiation.


Two-dimensional separation of alpha-naphthyl acetate esterases in human leucocytes and platelets.
Normal human leucocytes and platelets contain esterases which hydrolyse alpha-naphthyl acetate (alpha NA). Purified preparations from these cells were investigated by isoelectric focusing and subsequent polyacrylamide gradient gel electrophoresis at pH 9.0. Extractable alpha NA esterases were separated according to isoelectric point (pI) and molecular weight (MW). Monocytes, lymphocytes, granulocytes and platelets contain a unique pattern of alpha NA esterases, most of which can be inhibited by diisopropyl fluorophosphate (DFP; 0.1 mM). Their activity, however, is not affected by eserine (0.1 mM) or p-hydroxymercuribenzoate (1 mM). No protease activity of these enzymes was detected; it is likely that the majority constitute carboxylesterases (EC 188.8.131.52). Monocytes contain five alpha NA esterases which are additionally inhibited by bis(4-nitrophenyl)-phosphate (0.1 mM) and sodium fluoride (40 mM). PIs are in the range 5.7-6.2 and MWs are 145 000, 155 000, 250 000, 290 000 and 340 000. These enzymes are specific for monocytes. Platelets are characterized by a group of alpha NA esterases having pIs between 6.5 and 8.0, these corresponding to MWs ranging from 15 000 to 400 000.


pH-Sensitive carboxymethyl chitosan-modified cationic liposomes for sorafenib and siRNA co-delivery.
Combination of chemotherapeutic drug and small interfering RNA (siRNA) can affect multiple disease pathways and has been proven effective in suppressing tumor progression. Co-delivery of drug and siRNA within a same nanocarrier is a vital means in this field. The present study aimed at the development of a pH-sensitive liposome to co-deliver drug and siRNA to tumor region. Driven by the electrostatic interaction, the pH-sensitive material, carboxymethyl chitosan (CMCS), was coated onto the surface of the cationic liposome (CL) preloaded with sorafenib (Sf) and siRNA (Si). To evaluate whether the resulting CMCS-modified Sf and siRNA co-delivery cationic liposome (CMCS-SiSf-CL) enhanced antitumor efficiency after systematic administration, in vitro and in vivo experiments were evaluated in HepG2 cells and the H22 cells-bearing Kunming mice model. The experimental results demonstrated that CMCS-SiSf-CL was able to condense siRNA efficiently and protect siRNA from being degraded by serum and RNase. The release rate of Sf from CMCS-modified liposome exhibited pH-sensitive release behavior. Furthermore, in vitro cellular uptake results showed that CMCS-SiSf-CL yielded higher fluorescence intensity at pH 6.5 than at pH 7.4, and that siRNA could be delivered to tumor site by CMCS-SiSf-CL in vivo. The in vivo antitumor efficacy showed that CMCS-Sf-CL inhibits tumor growth effectively when compared with free Sf solution. In current experimental conditions, this liposomal formulation did not show significant toxicity both in vitro and in vivo. Therefore, co-delivering Sf with siRNA by CMCS-SiSf-CL might provide a promising approach for tumor therapy.


The Ki-67 Proliferation Index as a Marker of Time to Recurrence in Intracranial Meningioma.
There are examples of incongruence between the WHO grade and clinical course in meningioma patients. This incongruence between WHO grade and recurrence has led to search for other prognostic histological markers. To study the correlation between the Ki-67 proliferative index (PI), risk of recurrence, and recurrence rates in meningioma patients. We prospectively collected pathological diagnosis of de novo consecutive meningiomas. In total, we followed 159 patients with clinical controls until recurrence, death, or emigration. We estimated the correlation between risk of recurrence and Ki-67 PI when adjusted for age at diagnosis, sex, WHO grade, extent of surgical resection, and tumor location. We estimated the cumulative incidence of recurrence when considering death without recurrence a competing risk. We report recurrence rates per 100 person-years. A 1%-point increase of Ki-67 PI yielded a hazard ratio of 1.12 (95% CI: 1.01-1.24) in a multivariate analysis. The cumulative incidence of recurrence was 3% for Ki-67 0% to 4% vs 19% for Ki-67 > 4% meningiomas after 1 yr, but 24% vs 35%, respectively, after 10 yr. There was no significant difference in mean Ki-67 PI between nonrecurrent and recurrent meningioma in a 2-sample t-test (P = .08). The strongest relationship was detected between Ki-67 PI and time to recurrence: Ki-67 < 4% meningiomas recurred after median 4.8 yr, compared to 0.60 to 0.75 yr for patients with higher Ki-67 PI. Ki-67 PI was a marker for time to recurrence rather than a predictor of recurrence. Ki-67 PI may be utilized for patient tailored follow-up.


Interaction of probenecid with methotrexate transport and release in the isolated rat hepatocyte in suspension.
Probenecid has been shown to delay the plasma clearance of methotrexate in the rat and to reduce both hepatic and renal excretion of methotrexate in this animal model. In order to probe the mechanism by which probenecid alters hepatic excretion of the antifolate, studies assessed the effects of probenecid on transport, accumulation, distribution, and release of methotrexate in the rat hepatocyte in suspension. Probenecid was found to effectively inhibit methotrexate influx with a Ki of approximately 100 microM. Inhibition of methotrexate influx was accompanied by a reduction in methotrexate accumulation; with 200 microM probenecid, the levels of exchangeable and nonexchangeable intracellular methotrexate were reduced by 43.4 +/- 2.4 (S.E.) and 41.8 +/- 7.7%, respectively. As a consequence of reduced accumulation of the methotrexate substrate, the formation of cellular polyglutamate derivatives of methotrexate was likewise reduced. Concentrations of probenecid which inhibited methotrexate influx and accumulation by 70 to 80% did not markedly alter methotrexate efflux under conditions where efflux was effected by a washout procedure or by the presence of inducing agents, such as N6,O2'-dibutyryl cyclic adenosine 3':5'-monophosphate or alpha-agonists. These studies suggest that the inhibition of hepatic methotrexate secretion by probenecid in vivo is likely to be a consequence of interference with hepatic uptake of the antifolate rather than an interaction of probenecid and methotrexate at a hepatic "secretory" site.


Photoperiod and androgens act independently to induce spinal nucleus of the bulbocavernosus neuromuscular plasticity in the Siberian hamster, Phodopus sungorus.
In the Siberian hamster, Phodopus sungorus, short-day photoperiods induce the winter phenotype, which in males includes a decrease in the production of androgens and changes in physiology to inhibit reproduction. Motoneurones of the spinal nucleus of the bulbocavernosus (SNB) and their target muscles, the bulbocavernosus and the levator ani, a neuromuscular system involved in male copulation, also display seasonal plasticity in P. sungorus. It is not known whether the plasticity seen in the SNB system of gonadally intact hamsters is due to the effects of photoperiod per se, or to the photoperiod-induced changes in androgen production. To answer this question, we castrated adult male hamsters from long days and then implanted them with capsules containing either testosterone or blanks. Half of the hamsters from each hormone condition were moved into short photoperiod (8 : 16 h light/dark cycle) while the rest were maintained under long-day conditions (15 : 9 h light/dark cycle). After 15 weeks, many measures of the SNB system, such as somata size and weight of target muscles, responded only to androgen, not to photoperiod. However, there were effects of photoperiod on the neuromuscular junctions (NMJs) that were independent of androgen status. For example, the number of synaptic zones per NMJ and the area of the NMJs were significantly increased by short days and/or testosterone treatment. The two factors exerted an additive, rather than an interactive, effect on these measures. Another striated muscle, the extensor digitorum longus, which is present in both sexes and plays no specialized role in reproduction, displayed neither an effect of androgen nor of photoperiod on fibre size or NMJ structure. These results suggest that, in addition to androgenic effects on SNB plasticity, there is also an androgen-independent effect of photoperiod on the SNB neuromuscular system.


New thinking needed for emergency services.
Recent events in London and Manchester have highlighted the difficult and challenging role played by the emergency services. Their swift and professional response has drawn universal praise, but also raised concerns about reduced funding levels and job cuts against a heightened security threat. Transformational reforms are needed to improve our emergency services in a time of austerity.


Functional UDP-xylose transport across the endoplasmic reticulum/Golgi membrane in a Chinese hamster ovary cell mutant defective in UDP-xylose Synthase.
In mammals, xylose is found as the first sugar residue of the tetrasaccharide GlcAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-Ser, initiating the formation of the glycosaminoglycans heparin/heparan sulfate and chondroitin/dermatan sulfate. It is also found in the trisaccharide Xylalpha1-3Xylalpha1-3Glcbeta1-O-Ser on epidermal growth factor repeats of proteins, such as Notch. UDP-xylose synthase (UXS), which catalyzes the formation of the UDP-xylose substrate for the different xylosyltransferases through decarboxylation of UDP-glucuronic acid, resides in the endoplasmic reticulum and/or Golgi lumen. Since xylosylation takes place in these organelles, no obvious requirement exists for membrane transport of UDP-xylose. However, UDP-xylose transport across isolated Golgi membranes has been documented, and we recently succeeded with the cloning of a human UDP-xylose transporter (SLC25B4). Here we provide new evidence for a functional role of UDP-xylose transport by characterization of a new Chinese hamster ovary cell mutant, designated pgsI-208, that lacks UXS activity. The mutant fails to initiate glycosaminoglycan synthesis and is not capable of xylosylating Notch. Complementation was achieved by expression of a cytoplasmic variant of UXS, which proves the existence of a functional Golgi UDP-xylose transporter. A approximately 200 fold increase of UDP-glucuronic acid occurred in pgsI-208 cells, demonstrating a lack of UDP-xylose-mediated control of the cytoplasmically localized UDP-glucose dehydrogenase in the mutant. The data presented in this study suggest the bidirectional transport of UDP-xylose across endoplasmic reticulum/Golgi membranes and its role in controlling homeostasis of UDP-glucuronic acid and UDP-xylose production.


Repair of potentially lethal damage in rat mammary clonogens following irradiation in organoid culture.
In the course of investigations of radiogenic neoplasia in mammary cells in vivo, post-irradiation repair of potentially lethal damage (PLDR) was previously observed in mammary epithelial clonogens when they were irradiated and left in their tissue environment for 4-24 h after exposure. This type of PLDR increases the initial shoulder of the survival curve without significantly affecting its terminal slope. It has since been described in similarly treated thyroid and hepatic clonogens, and significantly exceeds that generally seen in most mammalian cells in culture. In this study, a ten-fold increase in the concentration of mammary clonogens which could be assayed was achieved by the isolation and short term culture (2-4 days) of mammary organoids (ductal and end-bud fragments). Assays of clonogen concentrations were carried out with cell suspensions prepared immediately following irradiation of 4-day organoid cultures or 24 h after irradiation of such organoid cultures. A near four-fold increase in clonogen survival was observed with the delay in assay after irradiation; this is comparable to the PLDR seen in mammary clonogens irradiated and left in situ for 4-24 h after exposure.


The comparative performance of for-profit and nonprofit home health care services in the US.
To determine, by way of an exhaustive, systematic, and comprehensive review and summary of all scientific published studies, whether or not there are any performance differences between private for-profit and private nonprofit home health care providers. The second objective is to discover the proportion of all research on this topic that is devoted to home health care services compared to all other health services providers. Computerized bibliographic searches of relevant databases and published indexes and abstracts were undertaken. They included Medline (Ovid and Pubmed versions), Web of Science (Social Sciences Citation Index and Science Citation Index), ABI/Inform, and Sociological Abstracts. Follow-up searches of reference lists in each article obtained from the computerized search were then completed. This systematic review retained for analysis all published studies that compared the performance of for-profit and nonprofit health care providers on access, quality, cost/efficiency, and/or amount of charity care, based on data collected after 1980. As a quality control measure only studies published in peer reviewed journals were included. Studies were coded according to the article's stated conclusions: for-profit superiority, nonprofit superiority, or no difference/mixed results. The comparative performance of for-profit and nonprofit home health service organizations is one of the most understudied areas of health care provider services in the US today. Only 6 of the over 1030 comparisons of the two concerned home health care. No data on this topic have been collected since 1991, and no articles about it have been published in a peer-reviewed journal since 1995. Research on the relative performance of for-profit and nonprofit home health care services is a research priority urgently in need of attention.


Recurrent Methotrexate-related Lymphoproliferative Disorder of the Lumbar Spine Origin: A Case Report.
Previously, we reported a relatively rare case of methotrexate-related lymphoproliferative disorder (MTX-LPD) that developed in the lumbar spine. At present, we report the follow-up of that case, presenting with relapse of MTX-LPD. The participant was a 75-year-old woman who was diagnosed with MTX-LPD of the lumbar spine and in whom remission was obtained 6 months after discontinuing methotrexate (MTX). At 12 months after remission, elevated levels of soluble interleukin-2 receptor, lymph node swelling on plain computed tomography (CT), and fluorodeoxyglucose uptake on positron emission tomography CT were observed, and recurrent MTX-LPD was diagnosed. Doxorubicin, bleomycin, vinblastine, and dacarbazine therapy was initiated, and partial remission was obtained 6 months later. In MTX-LPD, remission is often achieved following discontinuation of MTX alone; however, some patients do not improve, and some patients relapse, as seen in the present case. Such cases are treated using the standard regimen for the observed histologic subtype. Even after remission has been achieved, strict follow-up observation is needed for MTX-LPD. Furthermore, when signs of recurrence are observed during follow-up, practitioners should endeavor to cooperate with other specialists and act without delay.


Boosting Lithium-Ion Transport Kinetics by Increasing the Local Lithium-Ion Concentration Gradient in Composite Anodes of Lithium-Ion Batteries.
Constructing composite electrodes is considered to be a feasible way to realize high-specific-capacity Li-ion batteries. The core-double-shell-structured Si@C@TiO2 would be an ideal design for such batteries, considering that carbon (C) can buffer the volume change and TiO2 can constrain the structural deformation of Si. Although the electrochemical performance of the shells themselves is relatively clear, the complexity of the multishell heterointerface always results in an ambiguous understanding about the influence of the heterointerface on the electrochemical properties of the core material. In this work, a multilayer film model that can simplify and simultaneously expand the area of the heterointerface is used to study the heterointerfacial behavior. First, a multilayer film TiO2/C with different numbers of TiO2/C heterointerfaces is studied. It shows that the electrochemical performance is enhanced apparently by increasing the number of TiO2/C heterointerfaces. On the one hand, the TiO2/C heterointerface exhibits a strong lithium-ion storage capacity. On the other hand, the TiO2/C heterointerface appears to effectively promote the local Li-ion concentration gradient and thus boost the Li-ion transport kinetics. Then, TiO2/C is combined with Si to construct a composite anode Si/C/TiO2. An obvious advantage of TiO2/C over single TiO2 and C is observed. The utilization rate of Si is greatly improved in the first cycle and reaches up to 98% in Si/C/TiO2. The results suggest that the electrochemical performance of Si can be greatly manipulated by the heterointerface between the multishells.


Neoadjuvant chemotherapy affects molecular classification of colorectal tumors.
The recent discovery of 'molecular subtypes' in human primary colorectal cancer has revealed correlations between subtype, propensity to metastasize and response to therapy. It is currently not known whether the molecular tumor subtype is maintained after distant spread. If this is the case, molecular subtyping of the primary tumor could guide subtype-targeted therapy of metastatic disease. In this study, we classified paired samples of primary colorectal carcinomas and their corresponding liver metastases (n=129) as epithelial-like or mesenchymal-like, using a recently developed immunohistochemistry-based classification tool. We observed considerable discordance (45%) in the classification of primary tumors and their liver metastases. Discordant classification was significantly associated with the use of neoadjuvant chemotherapy. Furthermore, gene expression analysis of chemotherapy-exposed versus chemotherapy naive liver metastases revealed expression of a mesenchymal program in pre-treated tumors. To explore whether chemotherapy could cause gene expression changes influencing molecular subtyping, we exposed patient-derived colonospheres to six short cycles of 5-fluorouracil. Gene expression profiling and signature enrichment analysis subsequently revealed that the expression of signatures identifying mesenchymal-like tumors was strongly increased in chemotherapy-exposed tumor cultures. Unsupervised clustering of large cohorts of human colon tumors with the chemotherapy-induced gene expression program identified a poor prognosis mesenchymal-like subgroup. We conclude that neoadjuvant chemotherapy induces a mesenchymal phenotype in residual tumor cells and that this may influence the molecular classification of colorectal tumors.


A new pragmatic design for dose escalation in phase 1 clinical trials using an adaptive continual reassessment method.
A key challenge in phase I trials is maintaining rapid escalation in order to avoid exposing too many patients to sub-therapeutic doses, while preserving safety by limiting the frequency of toxic events. Traditional rule-based designs require temporarily stopping recruitment whilst waiting to see whether enrolled patients develop toxicity. This can be both inefficient and introduces logistic challenges to recruitment in the clinic. We describe a novel two-stage dose assignment procedure designed for a phase I clinical trial (STARPAC), where a good estimation of prior was possible. The STARPAC design uses rule-based design until the first patient has a dose limiting toxicity (DLT) and then switches to a modified CRM, with rules to handle patient recruitment during follow-up of earlier patients. STARPAC design is compared via simulations with the TITE-CRM and 3 + 3 methods in various toxicity estimate (T1-5), rate of recruitment (R1-2), and DLT events timing (DT1-4), scenarios using several metrics: accuracy of maximum tolerated dose (MTD), numbers of DLTs, number of patients enrolled and those missed; duration of trial; and proportion of patients treated at the therapeutic dose or MTD. The simulations suggest that STARPAC design performed well in MTD estimation and in treating patients at the highest possible therapeutic levels. STARPAC and TITE-CRM were comparable in the number of patients required and DLTs incurred. The 3 + 3 design often had fewer patients and DLTs although this is due to its low escalation rate leading to poor MTD estimation. For the numbers of declined patients and MTD estimation 3 + 3 is uniformly worse, with STARPAC being better in those metrics for high toxicity scenarios and TITE-CRM better with low toxicity. In situations including doses with toxicities both above and below 30%, the STARPAC design outperformed TITE-CRM with respect to every metric. When considering doses with toxicities both above and below the target of 30% toxicities, the two-stage STARPAC dose escalation design provides a more efficient phase I trial design than either the traditional 3 + 3 or the TITE-CRM design. Trialists should model various designs via simulation to adopt the most efficient design for their clinical scenario. Clinical Trials NCT03307148 (11 October 2017).


Blockade of telomerase reverse transcriptase enhances chemosensitivity in head and neck cancers through inhibition of AKT/ERK signaling pathways.
Head and Neck squamous cell carcinomas (HNSCC), characterized by the high frequency of local recurrence and distant metastases, is mostly related to highly malignant and resistant to apoptosis, resulting in significant insensitivity to chemotherapy. Telomerase reverse transcriptase (TERT), as the catalytic subunit of telomerase, was implicated in the telomerase-mediated cellular transformation, proliferation, stemness and cell survival. Moreover, overexpression of human TERT (hTERT) is reported to be correlated with advanced invasive stage of the tumor progression and poor prognosis. Here, we show that hTERT potentially mediated the apoptotic resistance and blockade of telomerase reverse transcriptase could enhance chemosensitivity in head and neck cancers. Mechanistically, hTERT interacts with the phosphorylation of AKT and ERK to suppress the expression of p53, ultimately, leading to modulation of the cellular sensitivity to chemotherapy. Thus, these findings suggest that hTERT targeting could be an attractive approach in combination with conventional chemotherapies for patients suffering from chemoinsensitivity or refractory HNSCC.


[Treatment of viral hepatitis (II). Treatment of chronic hepatitis C].
Hepatitis C virus infection is the principal cause of chronic liver disease, cirrhosis and hepatocellular carcinoma in the Western World. Chronic hepatitis C is often silent, most of the times discovered only by routine serologic or biochemical testing and the interval between infection and the development of cirrhosis exceed 30 years. Interestingly the complications of chronic hepatitis C virus infection can be prevented by antiviral therapy. At present, the combination of pegylated interferon-alfa and ribavirina has become the standard treatment of chronic hepatitis C. The management of HCV infection in "special populations" (HIV coinfection and HCV therapy-experienced patient) has improved significantly over the past few years, through a better knowledge of the disease and the publication of several clinical trials performed in these patients. At presents, a number of new anti-HCV therapies are in development. Future drugs for HCV infection might make possible to eradicate HCV in future.


Differences in virus prevalence and load in the hearts of patients with idiopathic dilated cardiomyopathy with and without immune-mediated inflammatory diseases.
Infections with cardiotrophic viruses and immune-mediated responses against the heart have been suggested to play a dominant role in the pathogenesis of idiopathic dilated cardiomyopathy (DCM). Furthermore, immune-mediated inflammatory diseases (IMIDs) may result in DCM. It has not previously been assessed whether DCM patients with and without an IMID have different prevalences and quantities of cardiotrophic viruses in the heart. Therefore, we compared the profiles of cardiotrophic viruses in heart tissue of DCM patients with and without an IMID. Serum and myocardial tissue samples were obtained from 159 consecutive patients with DCM and 20 controls. Patients were subdivided into three groups, the first two based on the presence (n = 34) or absence (n = 125) of an IMID and the third being a control group. The parvovirus B19 virus genome was detected in equal quantities in the non-IMID DCM patients (100/125) and the control group (15/20) but in lower quantities in the IMID patients (21/34, P = 0.02). Both the non-IMID and IMID DCM patients demonstrated increased myocardial inflammation compared to controls: 12.5 ± 1.8 and 14.0 ± 3.2 CD45-positive inflammatory cells, respectively, versus 5.1 ± 0.7 for the controls (P < 0.05 for both). Importantly, significantly higher parvovirus B19 copy numbers could be amplified in non-IMID than in IMID patients (561 ± 97 versus 191 ± 92 copies/μg DNA, P < 0.001) and control subjects (103 ± 47 copies/μg DNA, P < 0.001). The present study shows decreased parvovirus B19 prevalence and copy numbers in hearts of DCM patients with an IMID compared to those without an IMID. These findings may suggest that DCM patients with an IMID have a different pathophysiologic mechanism from that which is present in the virus-induced form of DCM.


Efficacy of the Combined Administration of Systemic and Intra-Articular Tranexamic Acid in Total Hip Arthroplasty Secondary to Femoral Neck Fracture: A Retrospective Study.
Total hip arthroplasty (THA) is associated with substantial blood loss in the postoperative course. Tranexamic acid (TXA) is a potent antifibrinolytic agent, routinely administered by intravenous (IV) and topical (intra-articular, IA) route, which can possibly interrupt the cascade of events due to hemostatic irregularities close to the source of bleeding. However, scientific evidence of combined administration of TXA in THA secondary to a femoral neck fracture is still meagre. The present study aims to compare the patients who were administered combined IV and topical TXA with a control group in terms of blood loss, transfusion rate, and incidence of deep vein thrombosis (DVT) and thromboembolism (TE). Patients and Methods. 195 patients with femoral neck fracture underwent THA and were placed into two groups: (1) IV and IA TXA group which had 58 patients and (2) no TXA control group which had 137 patients. In the TXA group, 1 g IV TXA was administered 30 minutes before incision, and 1 g IA TXA was administered intraoperatively after fascia closure. No drains were placed, and soft spica was applied to the hip. Combined usage of IV and IA TXA showed better results when compared to the control group in terms of blood transfusion rate (31%) and hemoglobin drop (28%). No cases of DVT or TE were noted among the two study groups. Combined use of IV and IA TXA provided significantly better results compared to no TXA use with respect to all variables related to postoperative blood loss in THA. Moreover, TXA use is safe in terms of incidence of symptomatic DVT and TE.


An overlap of granulomatosis with polyangiitis and eosinophilic granulomatosis with polyangiitis.
We present a case report of overlap of granulomatosis with polyangiitis (GPA; formerly known as Wegener's granulomatosis) and eosinophilic granulomatosis with polyangiitis (EGPA; formerly known as Churg-Strauss syndrome). We report a 45-year-old female who presented with rapidly progressive renal failure associated with fever, polyarthralgia, and respiratory symptoms with cytoplasmic antineutrophilic cytoplasmic antibody (ANCA) and proteinase (PR-3) antigen positivity. Computerized tomography scan of the chest showed diffuse alveolar hemorrhage with renal biopsy revealing pauci-immune necrotizing crescentic glomerulonephritis with intense eosinophilic infiltration suggestive of eosinophilic GPA (EGPA). Our patient had ANCA-associated vasculitis (AAV) with features suggestive of both GPA and EGPA. She was treated with methylprednisolone and cyclophosphamide and attained remission after 2 weeks of therapy. This is a rare report of a patient with AAV having features of both EGPA and GPA.


Regulation in Escherichia coli of the porin protein gene encoded by lambdoid bacteriophages.
Specialized lambda transducing phages carrying the cloned lc porin gene from the lambdoid bacteriophage PA-2, including various amounts of a sequence 5' to the start of transcription, were used to study the regulation of the porin gene. It was found that a cyclic AMP receptor protein consensus binding site 65 base pairs 5' to the start of transcription was required for catabolite repression of lc but was not sufficient for maximum expression under derepressing conditions. A sequence located more than 209 base pairs 5' to the start of transcription was necessary for maximum expression. By manipulating the copy number of the lc gene and the temperature and by measuring both the rate of synthesis of mRNA and the amount of Lc protein in the outer membrane, it was determined that the expression of lc is regulated primarily at the level of transcription and that expression is not autoregulated. Evidence is also presented that the silent phage porin gene nmpC of Escherichia coli K-12 is transcribed to the same extent as lc even though it does not give rise to a stable pool of mRNA. The structure of the 5' end of lc and nmpC is similar to that of ompF, and a model for transcriptional regulation is presented which may apply to all of these porin genes.


Chitosan-Based Nano Systems for Natural Antioxidants in Breast Cancer Therapy.
Breast cancer is a major cause of death globally, accounting for around 13% of all deaths. Chemotherapy, the common treatment for cancer, can have side effects that lead to the production of reactive oxygen species (ROS) and an increase in oxidative stress in the body. Antioxidants are important for maintaining the health of cells and helping the immune system function properly. They play a crucial role in balancing the body's internal environment. Using natural antioxidants is an alternative to mitigate the harmful effects of oxidative stress. However, around 80% of natural antioxidants have limited effectiveness when taken orally because they do not dissolve well in water or other solvents. This poor solubility affects their ability to be absorbed by the body and limits their bioavailability. One strategy that has been considered is to increase their water solubility to increase their oral bioavailability. Chitosan-based nanoparticle (CSNP) systems have been extensively explored due to their reliability and simpler synthesis routes. This review focuses on the various methods of chitosan-based nanoformulation for developing effective oral dosage forms for natural antioxidants based on the pharmacokinetics and pharmacodynamics properties. Chitosan (CS) could be a model, because of its wide use in polymeric NPs research, thus providing a better understanding of the role of vehicles that carry natural antioxidants in maintaining the stability and enhancing the performance of cancer drugs.


[Bladder pheochromocytoma and pregnancy. A case report].
The authors report the case of a 31-year old patient who successfully completed a pregnancy despite unsuspected bladder pheochromocytoma. After delivery, the patient required care post-partum due to serious hemodynamic problems. Hypertension had been attributed to toxemia of pregnancy. The authors recall the diagnostic difficulties of tumors of this type, and the means which can be used for topographical diagnosis and the precautions to be taken before this tumor can be treated surgically.


Pharmacokinetics of mycophenolate mofetil in renal transplant recipients on peritoneal dialysis.
Little is known about the pharmacokinetics of mycophenolatic acid (MPA) in the early posttransplant period after renal transplantation. We studied the impact of peritoneal dialysis on the pharmacokinetics of MPA in 5 patients following renal transplantation (3-6 weeks after transplantation). Three patients had a glomerular filtration rate (GFR) of less than 10 ml/min, 1 patient had a GFR of 32, and 1 of 58 ml/min. Pharmacokinetics of MPA and its main metabolite mycophenolic acid glucuronide (MPAG) were studied on 2 consecutive days (12-hour intervals: with and without peritoneal dialysis). Dosing of MPA was 2 x 1 g/day. MPA and MPAG concentrations were determined by HPLC methods. After initiation of peritoneal dialysis in patients with severe renal impairment (GFR < 10 ml/min) MPA area under the concentration curve (AUC) decreased substantially (15-59%). The calculated clearance of MPA was higher (14.6 vs 8.1 ml/min/kg) on the day of peritoneal dialysis than during the dwell-free day. MPAG-AUC decreased up to 26% in these patients. In both patients with a GFR > 30 ml/min we observed an increase of MPA-AUC on the day of peritoneal dialysis and a decreased MPA clearance. MPAG-AUCs remained stable. Patients with a reduced GFR had much higher MPAG values than patients with a GFR 30 ml/l, however, we did not observe any differences for the MPA levels. We found a significant inverse correlation between GFR and MPAG-AUC (r = 0.91, p < 0.05). While MPA was found only in traces in the peritoneal ultrafiltrate, the cumulative amount of MPAG removed by peritoneal dialysis reached up to 2 g per 12 hours, representing up to 1.2 g of MPA. This is the first report describing a reduction of MPA- and MPAG-AUC during peritoneal dialysis. Further studies are needed to better understand the pharmacokinetics of mycophenolat mofetil during peritoneal dialysis.


Tin, The Enabler-Hydrogen Diffusion into Ruthenium.
Hydrogen interaction with ruthenium is of particular importance for the ruthenium-capped multilayer reflectors used in extreme ultraviolet (EUV) lithography. Hydrogen causes blistering, which leads to a loss of reflectivity. This problem is aggravated by tin. This study aims to uncover the mechanism via which tin affects the hydrogen uptake, with a view to mitigation. We report here the results of a study of hydrogen interaction with the ruthenium surface in the presence of tin using Density Functional Theory and charge density analyses. Our calculations show a significant drop in the energy barrier to hydrogen penetration when a tin atom or a tin hydride molecule (SnHx) is adsorbed on the ruthenium surface; the barrier has been found to drop in all tested cases with tin, from 1.06 eV to as low as 0.28 eV in the case of stannane (SnH₄). Analyses show that, due to charge transfer from the less electronegative tin to hydrogen and ruthenium, charge accumulates around the diffusing hydrogen atom and near the ruthenium surface atoms. The reduced atomic volume of hydrogen, together with the effect of electron⁻electron repulsion from the ruthenium surface charge, facilitates subsurface penetration. Understanding the nature of tin's influence on hydrogen penetration will guide efforts to mitigate blistering damage of EUV optics. It also holds great interest for applications where hydrogen penetration is desirable, such as hydrogen storage.


An unusual case of aorta-right atrial tunnel with windsock aneurysm: imaging, diagnosis and treatment.
The first successfully diagnosed and treated case of aorta-right atrial tunnel was reported by Coto et al. in 1980. The most common cause of aorta-right atrial tunnel is a ruptured aneurysm of the sinus of Valsalva. Sinus of Valsalva aneurysms had been reported as early as 1840 by Thurnam; these were diagnosed at autopsy. With the advances in radiology, many cases of aorta-right atrial tunnel have been reported since then, each with its own subtle variations. We report on a unique case of aorta-right atrial tunnel with a windsock aneurysm in the right atrium. A 55-year-old male presented with abdominal pain and the chest X-ray revealed cardiomegaly. On further investigation with echocardiography and computed tomography angiography, there was an incidental aorta-right atrial tunnel with a windsock aneurysm in the right atrium. He was treated successfully with surgery. A similar case has been reported only once before by Iyisoy et al. in 2014.


Incidence of isoniazid acetylation phenotypes in North Indians.
Isoniazid acetylation phenotypes were determined in 110 cases (55 of pulmonary tuberculosis and 55 of nontubercular chest diseases) by sulphadimidine acetylation test (Bratton and Marshall method). Cases with more than 65% of acetylated sulphadimidine in urine at 6th h were classified as fast acetylators, those with less than 50% as slow acetylators and others with values between 50-65% as intermediate acetylators. There were 39.09% fast, 46.36% intermediate and 14.55% slow acetylators. Possible factors for difference in results from other Indian studies have been discussed. Sulphadimidine acetylation showed no variation due to presence of disease, age, sex, religion, place of origin, height, weight and smoking habits. However, 79% of those who took alcohol regularly turned out to be fast acetylators.


PDK4 Inhibition Ameliorates Melatonin Therapy by Modulating Cerebral Metabolism and Remyelination in an EAE Demyelinating Mouse Model of Multiple Sclerosis.
We recently showed that melatonin ameliorates the severity of experimental autoimmune encephalomyelitis (EAE), an animal model of MS. However, efficiency of melatonin therapy was associated with side effects, manifested by slowing down of remyelination, through increasing the inhibitory effects of brain pyruvate dehydrogenase kinase-4 (PDK-4) on pyruvate dehydrogenase complex (PDC), a key enzyme in fatty acid (FA) synthesis during remyelination. In this study, we investigated the metabolic profile of FA synthesis using combination therapy of melatonin and diisopropylamine dichloroacetate (DADA), a PDK4 inhibitor, in EAE mice. Disease progression was monitored by recording the disability scores. Immunological, oligodendrogenesis and metabolic factors were also evaluated. Results showed that combination therapy of melatonin and DADA significantly reduced EAE disability scores, compared to melatonin, whereas DADA alone did not have any effect. In addition, co-therapy inhibited pro-inflammatory while increasing anti-inflammatory cytokines, significantly better than melatonin alone. Moreover, administration of combination drugs recovered the declined expression of oligodendrocytic markers in EAE, more potently than melatonin. Furthermore, co-therapy affected cerebral energy metabolism by significantly reducing lactate levels while increasing N-acetylaspartate (NAA) and 3-hydroxy-3-methyl-glutaryl-coenzyme-A reductase (HMGCR) levels. Finally, while melatonin increased lactate and PDK4 expression levels and greatly reduced PDC activity, co-therapy significantly restored PDC function while reducing the lactate levels. In summary, administration of melatonin with DADA increased the efficiency of melatonin treatment by eliminating the inhibitory effects of PDK4 on PDC's function, a critical step for proper FA synthesis during remyelination.


Status of marine biomedical research.
A meeting on Marine Biomedical Research, sponsored by the National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health and the Smithsonian Institution Museum of Natural History, was attended by approximately 125 scientists, directors and representatives from many of the country's marine biological laboratories, and government agencies whose interests and responsibilites are in the marine biology and health areas. The purpose of the meeting was to explore the undeveloped research opportunities in the area of marine biology for the advancement of our understanding of human health problems and to provide information on the current status of marine biology laboratories. The meeting was devoted to presentations and discussions in four general areas: (1)Marine Species as Models for Human Disease; (2)Environmental Carcinogenesis and Mutagenesis; (3)Human Health and the Marine Environment--infectious agents and naturally occurring and foreign toxins; and (4)Drugs from the seas. Representatives from twelve of the country's approximatley 40 marine laboratories discussed their organization, developmental history, scientific programs, facilities, and present status of their support. The presentations served as a background and stimulated very lively analytical and constructive discussions of the undeveloped research and education potential residing in the marine environment and biological laboratories for a better understanding of many human health problems; some scientific areas that should be developed to realize this potential; and the needs and problems of marine laboratories that require attention and support if they are to survive and realize their possibilities.


Pharmacokinetics of indomethacin in the premature infant.
Indomethacin (I) pharmacokinetics was evaluated in 6 premature infants who received the drug for treatment of patent ductus arteriosus. Administered by oral or rectal route, I (0.2 mg/kg/24 h X 3) was promptly absorbed with peak plasma concentrations attained within 1 and 3 h. The elimination of I appeared to follow two compartment open model kinetics, with terminal plasma half-lives ranging from 30 to 90 h. Apparent plasma clearance values were between 0.076 and 0.335 ml/min/kg. Ductal closure was observed in 4 of the 6 infants. Data point to a possible relationship between therapeutic effects and I plasma concentrations.


Radioimmunoassay of serum-conjugated deoxycholic acid.
A specific, sensitive, and reliable radioimmunoassay for serum-conjugated deoxycholic acid has been developed with antiserum obtained after immunization of rabbits with deoxycholic acid--bovine serum albumin conjugate. The displacement curve of glyco [3H] deoxycholic acid was linear on a logit-log plot from 7.5 to 320 pmol of unlabeled glycodeoxycholic acid. At 50% displacement of bound label, the cross-reactivity of taurodeoxycholic acid was 100%, deoxycholic acid 30%, taurocholic acid 3%, and glycocholic acid 2%. No cross-reactivity was observed with free cholic acid, conjugated or free chenodeoxycholic acids and conjugated or free lithocholic acids. Fasting serum-conjugated deoxycholic acid concentrations in 10 healthy volunteers ranged from 0.18 to 0.92 mumol/1. Over a period of 5 hours following 0.5 g oral cholate administration the serum-conjugated deoxycholic acid concentration did not change in 5 fasting healthy persons, whereas an initial increase of serum cholic acid was observed.


First tergal structures for the fossil stonefly genus Largusoperla (Plecoptera: Perlidae): a new species and a new tribe of Acroneuriinae.
Based on a well-preserved adult male specimen from mid-Cretaceous Burmese amber, a new species of the fossil stonefly genus Largusoperla Chen et al. 2018, L. crassus sp. nov. is described. The male holotype exhibits asymmetrical paraprocts and conspicuous tergal characters, previously unknown for the genus. A new tribe of Acroneuriinae, Largusoperlini trib. nov. is proposed for this male adult based on the presence of these newly observed tergal characters.


Solubility of antimycotics: a problem in in vitro experiments.
An investigation of how miconazole nitrate dissolved in dimethylformamide in initial concentrations of 1,000, 500, and 100 microgram/ml may alter its concentration with storage time, is presented. The determination of miconazole nitrate was performed with high pressure liquid chromatography. After 8 hours the 1,000 microgram/ml solution was milky and the concentration of miconazole had fallen significantly. It was concluded that test agar plates or agar tubes must be made with freshly prepared and clear stock solutions, otherwise false MIC's may be obtained.


Analysis of Measurement Errors in Passive Sampling of Porewater PCB Concentrations under Static and Periodically Vibrated Conditions.
Although the field of passive sampling to measure freely dissolved concentrations in sediment porewater has been sufficiently advanced for organic compounds in the low- to midrange of hydrophobicity, in situ passive sampling of strongly hydrophobic polychlorinated biphenyls (PCBs) is still challenged by slow approach to equilibrium. Periodic vibration of polyethylene (PE) passive samplers during exposure has been previously shown to enhance the mass transfer of polycyclic aromatic hydrocarbons (PAHs) from sediment into PE. Herein, we used a new vibrating platform, developed based on our earlier platform design, to demonstrate the effectiveness of periodic vibration for strongly hydrophobic compounds such as hexa-, hepta-, and octachloro-PCBs. Uptake of PCBs in PE after 7, 14, 28, and 56 days under different vibration modes was compared to that under static and mixed laboratory deployments. All PCBs reached within 95-100% of equilibrium after 56 days of deployment in the system vibrated briefly every 2 min, while none of the congeners achieved more than 50% of equilibrium in static deployment for the same period. Periodic vibration also increased the dissipation rate of four performance reference compounds (PRCs) from passive samplers. Higher fractional loss of PRCs and closer approach to equilibrium in the vibrated deployment resulted in estimation of corrected porewater concentrations that were statistically indistinguishable from the true equilibrium values even after a short 7-day deployment. Porewater concentrations of the strongly hydrophobic PCB congeners were overestimated by up to an order of magnitude in the static passive sampler after the same deployment time.


On the possibility to affect the course of glycaemia, insulinaemia, and perceived hunger/satiety to bread meals in healthy volunteers.
Frequent hyperglycaemia is associated with oxidative stress and subclinical inflammation, and thus increased risk of cardiovascular disease. Possibilities of modulating glycaemia, insulinaemia and perceived satiety for bread products were investigated, with emphasis on the course of glycaemia expressed as a glycaemic profile (defined as the duration of the glucose curve above the fasting concentration divided by the incremental glucose peak). For this purpose white wheat bread was supplemented with whole grain corn flour with an elevated amylose content and different types and levels of guar gum. The bread products were characterised in vitro for release of starch degradation products and content of resistant starch. Fibre related fluidity following enzyme hydrolysis was also studied. By combining medium weight guar gum and whole grain corn flour with an elevated amylose content, the course of glycaemia, insulinaemia and subjective appetite ratings were improved compared to the reference white wheat bread. In addition, the combination beneficially influenced the content of resistant starch. Fluidity measurements showed potential to predict the glycaemic profile.


Modulation of cellular immune response by orbifloxacin in noninfected and E. coli-infected mice.
The studies were conducted on noninfected and Escherichia (E) coli-infected mice treated with orbifloxacin administered orally 10 times at 24-hr intervals at a dose of 2.5 mg/kg. Orbifloxacin did not change the activity of peritoneal macrophages in noninfected mice. Administration of orbifloxacin in E. coli-infected mice modulated the effects of infection on the percentage of phagocyting macrophages, the percentage of NBT-positive cells, and nitric oxide production. Orbifloxacin did not affect the synthesis and release of interleukin-1 by macrophages. Orbifloxacin exerted a modulating effect on the subsets of lymphocytes in thymus, spleen, and mesenteric lymph node cells in noninfected and E. coli-infected mice.


Emodin induces hepatocellular carcinoma cell apoptosis through MAPK and PI3K/AKT signaling pathways in vitro and in vivo.
Emodin is an active ingredient derived from root and rhizome of Rheum palmatum L and many studies have reported that it exhibits anticancer effects in a number of human tumors. However, there is little information demonstrating the possible effects of emodin on the proliferation and apoptosis of hepatocellular carcinoma (HCC). In the present study, we show that emodin may inhibit the proliferation of SMMC-7721 cells in a dose- and time-dependent manner and induced apoptosis of cells in a concentration-dependent manner after treatment for 24 h. Moreover, we further discovered that the possible molecular mechanisms involved may relate to the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/AKT signaling pathways. Emodin may induce the phosphorylation of extracellular-signal-regulated kinase (ERK) and p38 while mildly suppressed the expression of p-c-Jun-N-terminal kinase (p-JNK). However, emodin did not affect the expression of the total (t)-ERK, t-p38 or t-JNK. Furthermore, emodin also suppressed the activation of p-AKT, but not the t-AKT. In vivo, we found that emodin suppressed tumor growth in experimental mice without an obvious change in body weight, which may work through the antiproliferation and apoptosis inducing effects. Moreover, emodin improves the liver and kidney function in mice, revealing that emodin may improve the life quality of the mice with implanted tumors. In conclusion, the above findings indicate that emodin may be a potentially effective and safe drug to induce apoptosis of HCC.


Lipoxin A4 Suppresses Estrogen-Induced Epithelial-Mesenchymal Transition via ALXR-Dependent Manner in Endometriosis.
Epithelial-mesenchymal transition (EMT) is essential for embryogenesis, fibrosis, and tumor metastasis. Aberrant EMT phenomenon has been reported in endometriotic tissues of patients with endometriosis (EM). In this study, we further investigated the molecular mechanism of which lipoxin A4 (LXA4) suppresses estrogen (E2)-induced EMT in EM. The EMT markers were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot in eutopic endometrial epithelial cells (EECs) or investigated by immunohistochemistry and qRT-PCR in endometriotic lesion of EM mice. The invasion and migration under different treatments were assessed by transwell assays with or without Matrigel. The messenger RNA (mRNA) and activities of matrix metalloproteinase 2 (MMP-2) and MMP-9 were determined by qRT-PCR and gelatin zymography, respectively. Luciferase reporter assay was used to measure the activity of zinc finger E-box binding homeobox 1(ZEB1) promoter. The level of E2 in endometriotic tissues was assessed by enzyme-linked immunosorbent assay. In eutopic EECs, stimulatory effects of E2 on EMT progress, migration, and invasion were all diminished by LXA4. Lipoxin A4 reduced E2-induced ZEB1 promoter activity. Lipoxin A4 also attenuated the phosphorylation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase induced by E2. Co-incubation with Boc-2 rather than DMF antagonized the influence of LXA4. Animal experiments showed that LXA4 inhibited the EMT progress, MMP expression, and proteinase activities of endometriotic lesion in an LXA4 receptor (ALXR) manner, which suppressed the progression of EM. ZEB1 mRNA expression was upregulated and well correlated with E2 level in human endometrium. Lipoxin A4 suppresses E2-induced EMT via ALXR-dependent manner in eutopic EECs, which reveals a novel biological effect of LXA4 in EM.


Ischemic stroke on hormonal contraceptives: Characteristics, mechanisms and outcome.
Systemic contraceptives increase the risk of ischemic stroke but little is known about the characteristics, mechanisms and long-term outcome post stroke of patients on hormonal contraception. We sought to To assess characteristics and outcome of acute ischemic stroke (AIS) in young women using systemic hormonal contraceptives (SHC) and compare them to strokes in non-contraceptive users. Using the Acute STroke Registry and Analysis of Lausanne (ASTRAL), we analyzed demographics, risk factors, clinical, radiological and treatment data of consecutive female patients of <50 years between 2003 to 2015. We compared groups with and without SHC in a logistic regression analysis. Of the 179 female patients of <50 years during the observation period, 57 (39.6%) used SHC, 71.9% of whom, a combined oral contraceptive pill. On logistic regression contraceptive users were significantly younger but had comparable stroke severity. They had less migraine with aura and tobacco use, and more hyperlipidaemia. Also, contraceptive users had significantly less intra and extracranial stenosis and occlusion on arterial imaging, but more focal hypoperfusion on CT-perfusion. Undetermined mechanism of stroke was more frequent with SHC users, whereas rare mechanisms were more frequent in non-users. The contraceptive user group had a more favourable adjusted 12-month outcome with significantly fewer ischemic recurrences after stopping systemic contraception in all. Contraceptive users with ischemic strokes are younger and have lesser tobacco use and migraine with aura and more hyperlipidemia. Their stroke mechanism is more often undetermined using a standardised work-up, and their adjusted long-term outcome is more favourable with less stroke recurrence.


Further evolution toward effective therapy for acute ischemic stroke.
The effective treatment of acute ischemic stroke remains an important goal of modern medicine and substantive advances are occurring. Recently, thrombolytic therapy with tissue-type plasminogen activator was approved for selected patients with acute ischemic stroke when therapy is started within 3 hours of onset. Streptokinase therapy for acute ischemic stroke has not been shown to be effective and is associated with an increased risk of hemorrhage, although it was not evaluated as early after stroke onset as tissue-type plasminogen activator. Various types of neuroprotective interventions are effective in animal models, but none has yet been proven effective in patients. In the future, combinations of thrombolytic and neuroprotective drugs may be used to attempt maximum rates of recovery after acute ischemic stroke. For combination therapy to achieve its maximum potential, patients with acute ischemic stroke will have to be carefully selected and treated.


Genetic Diversity of Bovine Pestiviruses Detected in Backyard Cattle Farms Between 2014 and 2019 in Henan Province, China.
Bovine pestiviruses include Pestivirus A (BVDV-1), Pestivirus B (BVDV-2), and Pestivirus H, which was originally called HoBi-like pestivirus. We conducted an epidemiological investigation for pestiviruses circulating in backyard cattle farms in central China. RT-PCR assays and sequences analysis were conducted on 54 nasal swabs, 26 serum samples, and three lung samples from cattle with respiratory infections and identified 29 pestivirus strains, including 24 Pestivirus A and five Pestivirus H strains. Phylogenetic analysis based on partial 5'-UTR and Npro sequences showed that the genotypes of 24 Pestivirus A strains included Pestivirus A 1b (six isolates), Pestivirus A 1m (six isolates), Pestivirus A 1q (two isolates), Pestivirus A 1u (one isolates), and Pestivirus A 1o (nine isolates, a putative new sub-genotype). In addition, a single Pestivirus H agenotype included all five Pestivirus H strains. This study revealed extensive genetic variations within bovine pestivirus isolates derived from cattle in backyard farms in Central China, and this epidemiological information improves our understanding of the epidemics of bovine Pestiviruses, as well as will be useful in designing and evaluating diagnostic methods and developing more effective vaccines.


Parkinson's Disease EMG Data Augmentation and Simulation with DCGANs and Style Transfer.
This paper proposes two new data augmentation approaches based on Deep Convolutional Generative Adversarial Networks (DCGANs) and Style Transfer for augmenting Parkinson's Disease (PD) electromyography (EMG) signals. The experimental results indicate that the proposed models can adapt to different frequencies and amplitudes of tremor, simulating each patient's tremor patterns and extending them to different sets of movement protocols. Therefore, one could use these models for extending the existing patient dataset and generating tremor simulations for validating treatment approaches on different movement scenarios.


Spatial and Temporal Variation of Drought Based on Satellite Derived Vegetation Condition Index in Nepal from 1982⁻2015.
Identification of drought is essential for many environmental and agricultural applications. To further understand drought, this study presented spatial and temporal variations of drought based on satellite derived Vegetation Condition Index (VCI) on annual (Jan⁻Dec), seasonal monsoon (Jun⁻Nov) and pre-monsoon (Mar⁻May) scales from 1982⁻2015 in Nepal. The Vegetation Condition Index (VCI) obtained from NOAA, AVHRR (National Oceanic and Atmospheric Administration, Advanced Very High Resolution Radiometer) and climate data from meteorological stations were used. VCI was used to grade the drought, and the Mann⁻Kendall test and linear trend analysis were conducted to examine drought trends and the Pearson correlation between VCI and climatic factors (i.e., temperature and precipitation) was also acquired. The results identified that severe drought was identified in 1982, 1984, 1985 and 2000 on all time scales. However, VCI has increased at the rate of 1.14 yr-1 (p = 0.04), 1.31 yr-1 (p = 0.03) and 0.77 yr-1 (p = 0.77) on the annual, seasonal monsoon and pre-monsoon scales, respectively. These increased VCIs indicated decreases in drought. However, spatially, increased trends of drought were also found in some regions in Nepal. For instance, northern areas mainly in the Trans-Himalayan regions identified severe drought. The foothills and the lowlands of Terai (southern Nepal) experienced normal VCI, i.e., no drought. Similarly, the Anomaly Vegetation Condition Index (AVCI) was mostly negative before 2000 which indicated deficient soil moisture. The exceedance probability analysis results on the annual time scale showed that there was a 20% chance of occurring severe drought (VCI ≤ 35%) and a 35% chance of occurring normal drought (35% ≤ VCI ≤ 50%) in Nepal. Drought was also linked with climates in which temperature on the annual and seasonal monsoon scales was significant and positively correlated with VCI. Drought occurrence and trends in Nepal need to be further studied for comprehensive information and understanding.


[Differential heat diffusion as a factor in the etiology of the caloric nystagmus phenomenon].
Despite the significance of the caloric vestibular test in clinical practice, the origin of the caloric nystagmus phenomenon is still unclear. Several theories which try to explain the functional pathways have been published. However, the bandwidth of the reaction pattern and response times from the start of stimulation to the first responses question their plausibility. Therefore, the present investigation examines and analyses the specific reaction pattern and associated response times in 84 patients. On the basis of this information a simplified computer simulation model involving lumped tissue parameters has been created to study the heat diffusion process during stimulation. Consequently, an attempt was made to utilize the simulated diffusion times to identify those anatomical structures which could participate in the origin of the caloric nystagmus phenomenon and we developed a new hypothesis about its origin.


Immune dysregulation in the functional gastrointestinal disorders.
Gastrointestinal conditions may be broadly classified into two: organic and functional disease, with functional disorders accounting for the majority of patients with chronic gastrointestinal symptoms. Functional gastrointestinal disorders (FGIDs) present with no obvious pathology or well-accepted biochemical mechanism and, as such, treatment strategies are limited and focus on symptoms rather than cure. Irritable bowel syndrome and functional dyspepsia are the most widely recognised FGIDs, and there is a growing body of evidence to suggest an underlying inflammatory phenotype in subsets with these conditions. Here, we discuss the current knowledge of immune involvement in FGIDs and the commonalities between the different manifestations of FGIDs and propose a new hypothesis, potentially defining an underlying immunopathological basis of these conditions.


Importance of cereal phytase activity for phytate phosphorus utilization by growing pigs fed diets containing triticale or corn.
In contrast to corn, wheat and triticale exhibit high phytase activities. This enzyme enhances phytic phosphorus availability, as demonstrated in pigs given wheat diets. To study the utilization of triticale phosphorus in pigs, the importance of dietary phytase content and the mineral and bone disorders related to high phytate feeding, a nutritional experiment was carried out in 12 growing pigs fed either a corn- or a triticale-based diet for 6 wk. The diets were almost identical except for the cereal component; their phosphorus contents were low (0.4%) and mainly phytic. The following parameters were measured: calcium and phosphorus balances, bone and plasma contents of calcium and phosphorus, plasma vitamin D metabolites and parathyroid hormone (PTH), bone bending moments and intestinal phosphatase activities. Both diets provoked a phosphorus deficiency, but hypophosphatemia occurred less rapidly, hypercalciuria and hypophosphaturia were less marked and phosphorus availability was greater when the triticale diet was fed. This was attributed to the high phytase content of triticale because intestinal phytase and alkaline phosphatase activities were similar in pigs fed either diet. Calcium absorption was not modified by calcium retention was greater for pigs fed triticale and led to higher bone scores. In conclusion, the higher the phytase activity of the diet, the greater the phytate P availability and the lower the bone-mineral disorders.