Proteomic alterations in the plasma of Beagle dogs induced by Toxocara canis infection.
Toxocara canis causes ocular larva migrans and visceral larva migrans in humans. Knowledge about the molecular mechanism of T. canis-hosts interaction is limited. The proteomic alterations in the plasma of Beagle dogs induced by T. canis infection were studied by the quantitative mass spectrometry-based data-independent acquisition (DIA). 418, 414 and 411 plasma proteins were identified at 24 h post-infection (hpi), 96 hpi and 36 days post-infection (dpi), including 6, 5 and 23 proteins with differential abundance, respectively. At 24 hpi, the altered proteins, retinoic acid receptor responder protein 2 (RARRES2), WD repeat-containing protein 1 (WDR1), moesin and filamin-A, may participate in pro-inflammatory reaction or promote larvae migration. At 96 hpi, the altered protein C and fibroleukin may maintain the stability of the coagulation system to protect the lung. At 36 dpi, the alterations of C-reactive protein (CRP), ficolin (FCN), complement factor H-related protein 5 (CFHR5) and other complements can affect the three traditional complement system, including the classic pathway, lectin pathway and alternative pathway. These proteins may play important roles in the interaction between T. canis and its definitive hosts. Further study on these altered proteins triggered by T. canis infection may discovery novel therapeutic or diagnostic targets for toxocariasis. SIGNIFICANCE OF THE STUDY: Toxocara canis is one of the globally distributed soil-transmitted helminths, which causes ocular larva migrans and visceral larva migrans in humans and a wide range of warm-blooded animals. T. canis adapts to different microenvironments by resisting and adjusting various biological processes of the hosts. Knowledge about the molecular mechanism of T. canis-hosts interaction is limited. Plasma proteins are good marker for monitoring the occurrence and development of diseases. The proteomic alterations in the plasma of Beagle dogs induced by T. canis infection were studied by the quantitative mass spectrometry-based data-independent acquisition (DIA) in this study. A total of 418, 414 and 411 plasma proteins were identified at 24 h post-infection (hpi), 96 hpi and 36 days post-infection, respectively. Ten protein with differential abundances were validated by using parallel reaction monitoring (PRM). Collectively, our deep proteomic analysis of plasma revealed that proteins alterations were affected by disease development, and proteomic analysis is an ideal method for quantifying changes in circulating factors on a global scale in response to pathophysiological perturbations such as T. canis infection.


Angiogenic factors in endometriosis.
Similar to tumor metastases, endometriotic implants require neovascularization to establish, grow, and invade. The peritoneal environment is ideally suited to provide a proangiogenic milieu. Nevertheless, endometriotic lesions are found only in a minority of reproductive-age women (approximately 10%) with retrograde menstruation. In this paper, we review the major cytokines, growth factors, steroid hormones, and eicosanoids responsible for angiogenesis in endometriosis. We postulate that interference with angiogenic principles expressed in the peritoneum may constitute novel therapeutic opportunities for the prevention, amelioration, or treatment of pelvic endometriosis.


On the interaction of oxovanadium(IV) with homocysteine.
The interaction of the VO2+ cation with homocysteine was investigated by electron absorption spectroscopy in aqueous solution at different metal-to-ligand ratios. The direct reduction of vanadate(V) solutions with homocysteine was also investigated. The results suggest that the interaction is different from that found in the case of cysteine and occurs through pairs of amino and carboxylate groups of the amino acid. The interaction of VO2+ with homocystine, the oxidation product of homocysteine, was also analyzed. The interest of the results in relation to vanadium metabolism and detoxification is briefly discussed.


The innate defense regulator peptides IDR-HH2, IDR-1002, and IDR-1018 modulate human neutrophil functions.
Although HDPs were originally hypothesized to act as antimicrobial agents, they also have been shown to broadly modulate the immune response through the activation of different cell types. We recently developed a series of novel, synthetic peptides, termed IDRs, which are conceptually based on a natural HDP, bovine bactenecin. We showed that IDR-1 and IDR-1002 protect the host against bacterial infections through the induction of chemokines. The objective of this study was to investigate the effects of the IDRs on various functions of human neutrophils. Here, we demonstrated that IDR-HH2, IDR-1002, and IDR-1018 modulated the expression of neutrophil adhesion and activation markers. Moreover, these IDRs enhanced neutrophil adhesion to endothelial cells in a β₂ integrin-dependent manner and induced neutrophil migration and chemokine production. The IDR peptides also increased the release of the neutrophil-generated HDPs (antimicrobial), human α-defensins, and LL-37 and augmented neutrophil-mediated killing of Escherichia coli. Notably, the IDRs significantly suppressed LPS-mediated neutrophil degranulation, the release of ROS, and the production of the inflammatory cytokines TNF-α and IL-10, consistent with their ability to dampen inflammation. As evidenced by the inhibitory effects of MAPK-specific inhibitors, IDRs activated the MAPK pathway that was required for chemokine production. In conclusion, our study provides novel evidence regarding the contribution of the IDR peptides to the innate immune response through the modulation of neutrophil functions. The results described here may aid in the development of IDRs as novel, anti-infective and immunomodulatory agents.


Clinical features and prognosis of patients with and without diabetes mellitus undergoing endovascular aortic aneurysm repair.
This study aimed to compare the clinical features and prognoses of patients with and without diabetes mellitus (DM) who underwent endovascular repair for aortic aneurysm (AA). We analyzed the clinical database of a prospective multicenter study, registering 929 patients who underwent their first endovascular AA repair in Japan between January 2016 and June 2018. The baseline characteristics and prognoses (including all-cause mortality and cardiovascular events) after repair were compared between the DM and non-DM groups. Prognoses were also compared between the groups after propensity score matching. In total, 226 patients (24.3%) had DM. Compared with non-DM patients, DM patients had higher pack-years of smoking (P = 0.011), higher body mass index (P = 0.009), lower high-density lipoprotein cholesterol levels (P = 0.038), higher triglyceride levels (P = 0.025), and lower left ventricular ejection fraction (P = 0.005). Meanwhile, the low-density lipoprotein cholesterol and blood pressure levels showed no significant intergroup difference (all P > 0.05). DM patients had a higher prevalence of myocardial infarction (P = 0.016), history of coronary revascularization (P = 0.015), and lower extremity artery disease (P = 0.019). Lesion characteristics and procedures were similar between the groups (all P > 0.05). DM patients had a higher risk of all-cause mortality and cardiovascular events than non-DM patients (both P < 0.001). Subsequent propensity score matching also demonstrated that DM patients had a significantly lower rate of overall survival (P = 0.001) and freedom from cardiovascular events (P = 0.010). The Kaplan-Meier estimates at 1 year for the overall survival were 85.6% (95% confidence interval [CI], 80.9% to 90.5%) and 94.3% (95% CI, 91.7% to 97.0%) for patients with and without DM, respectively. The corresponding estimates for freedom from cardiovascular events were 79.8% (95% CI, 74.5% to 85.5%) and 87.7% (95% CI, 84.2% to 91.3%), respectively. Among patients undergoing endovascular AA repair, those with DM had more cardiovascular risk factors. DM patients had a higher incidence rate of all-cause mortality and cardiovascular events. Matching analysis indicated that DM per se would be a risk factor for poor prognoses after AA repair.


Impact of protein malnutrition on histological parameters of experimentally infected animals with Giardia lamblia.
Giardiasis is one of the most common parasitic diseases worldwide, and the disease is an important cause of diarrhoea and malabsorption in children and immunosuppressed individuals. However, there is no evidence that characterises malnutrition as an aggravating factor for this disease. We evaluated changes in villi structures to examine the association between malnutrition and Giardia lamblia infection. We used 32 gerbils, divided into 4 groups: Control (CT) and Control Infected (CTIn), which each received a 20% protein diet, Malnourished (MN) and Malnourished Infected (MNIn), which each received a 5% protein diet. Groups CTIn and MNIn were inoculated with 1×10(6) trophozoites of G. lamblia, while the remaining groups were mock infected. Seven days post-infection, all groups were sacrificed, and the proximal portions of the small intestines were collected for the analysis of villus height, mucus area and extent of Giardia infection. Gerbils fed with a low-protein diet had significantly lower body weights. Malnourished infected animals presented significantly increased production of mucus, suggesting a synergism occurs between malnutrition and Giardiasis, potentially to control the adhesion of Giardia in the mucosa. Villus height was significantly lower in group MNIn compared to CTIn. This work suggests that malnutrition contributes to severity of Giardiasis by decreasing the intestinal absorption capacity via shortening of the villi.


Description of two new micropterous species of Monasavuhygia Brailovsky, 1996 from the Fiji and Solomon Islands and a key to species (Heteroptera: Coreidae: Colpurini).
The genus Monasavuhygia Brailovsky, 1996 is revised. Two new species collected in the Fiji Islands and Solomon Islands, respectively, are described in the Tribe Colpurini (Heteroptera: Coreidae). A key to the known species is included, with photographs of the dorsal habitus and female genital plates provided.


The intrinsic immunogenic properties of cancer cell lines, immunogenic cell death, and how these influence host antitumor immune responses.
Modern cancer therapies often involve the combination of tumor-directed cytotoxic strategies and generation of a host antitumor immune response. The latter is unleashed by immunotherapies that activate the immune system generating a more immunostimulatory tumor microenvironment and a stronger tumor antigen-specific immune response. Studying the interaction between antitumor cytotoxic therapies, dying cancer cells, and the innate and adaptive immune system requires appropriate experimental tumor models in mice. In this review, we discuss the immunostimulatory and immunosuppressive properties of cancer cell lines commonly used in immunogenic cell death (ICD) studies being apoptosis or necroptosis. We will especially focus on the antigenic component of immunogenicity. While in several cancer cell lines the epitopes of endogenously expressed tumor antigens are known, these intrinsic epitopes are rarely determined in experimental apoptotic or necroptotic ICD settings. Instead by far the most ICD research studies investigate the antigenic response against exogenously expressed model antigens such as ovalbumin or retroviral epitopes (e.g., AH1). In this review, we will argue that the immune response against endogenous tumor antigens and the immunopeptidome profile of cancer cell lines affect the eventual biological readouts in the typical prophylactic tumor vaccination type of experiments used in ICD research, and we will propose additional methods involving immunopeptidome profiling, major histocompatibility complex molecule expression, and identification of tumor-infiltrating immune cells to document intrinsic immunogenicity following different cell death modalities.


Integration of mechanical cell disruption and fluidised bed recovery of G3PDH from unclarified disrupted yeast: a comparative study of the performance of unshielded and polymer shielded dye-ligand chromatography systems.
The development of a simplified process for the simultaneous disruption and direct selective purification of intracellular proteins from unclarified yeast disruptate has been investigated. The recovery of glyceraldehyde 3-phosphate dehydrogenase (G3PDH) from baker's yeast was selected as a potential demonstration of the generic applicability and practical feasibility of this integrated technique. The application of an adsorbent characterised by high density (UpFront steel-agarose; rho=2.65g ml(-1)) facilitated the combining of cell disruption operation (bead milling of 50% ww/v of yeast suspension at 7.2 lh(-1)) with fluidised bed dye-ligand (Cibacron Blue 3GA) adsorption operated immediately downstream of the disrupter. The adoption of a polymer shielded, dye-ligand technique advanced recovery efficiency. It was demonstrated that G3PDH could be recovered with a yield of 67.5% bound activity and a specific activity of 40.2IU mg(-1), after a single step elution with 0.15M NaCl. The generic application of this approach has been evaluated.


Inulin-type fructans with different degrees of polymerization improve lipid metabolism but not glucose metabolism in rats fed a high-fat diet under energy restriction.
Inulin-type fructan ameliorates metabolic diseases associated with obesity in animals. However, relatively little information is available on the comparative effects of inulins with different degree of polymerization (DP) on the lipid or glucose metabolism. The objective of this study was to investigate the effect of inulins with various DP on metabolic disorders associated with obesity in rats fed a high-fat diet under food restriction. Rats were fed a high-fat diet supplemented with 5 % inulin-GR (Raftiline GR), inulin-Tokachi (Tokachi), or inulin-HP (Raftiline HP) without cellulose for 28 days at normal energy intakes or 14.5 % energy restriction. Under food restriction, the dietary inulin-Tokachi (mean DP 15) and -HP (mean DP 24), but not -GR (mean DP 10), reduced (p < 0.05) the serum cholesterol and triglyceride levels, and liver triglyceride concentration in rats, compared to the control diet. The cecal neutral steroid, bile acid, and propionate concentrations in the Tokachi and HP groups were higher (p < 0.05) than in the CONT group, and the cecal Bifidobacterium count in the Tokachi group was higher (p < 0.05) than in the other groups. Findings suggest that, depending on DP, dietary supplementation with inulin (DP 15 or DP 24) in rats fed a high-fat diet, regardless of food intake, positively modulates lipid metabolism and fecal microbiota but not glucose metabolism.


Cardiac-derived neutrophil chemotactic factors: detection in coronary sinus effluents of patients undergoing myocardial revascularization.
Recent studies from our laboratory have demonstrated the release of neutrophil chemotactic factors from isolated rabbit hearts perfused with cardioplegic solutions and from ischemic dog hearts after coronary artery occlusion for 1 hour. On the basis of these animal studies, a test is now made of the hypothesis that neutrophil chemotactic factors are released by myocardial tissues of patients who undergo surgical myocardial revascularization. By means of modified Boyden chambers, the levels of neutrophil chemotactic factors were measured in effluent collected from the coronary sinuses of six patients undergoing cardiopulmonary bypass during periods of cold cardioplegia. Plain cardioplegic solutions were also analyzed. The standard formyl-methionyl-leucyl-phenylalanine, a stimulant of neutrophil recruitment, was used as a positive control solution. Results indicated the recovery of significantly high levels of neutrophil chemotactic factors in patient samples (i.e., 128% +/- 19% of formyl-methionyl-leucyl-phenylalanine) compared with control plain cardioplegic solution (less than 5% of formyl-methionyl-leucyl-phenylalanine) (p less than 0.0001). A standard checkerboard analysis indicated that the observed activity is chemotactic (i.e., directed migration) and not chemokinetic (i.e., random migration). This study also showed that these factors are proteins of a molecular weight in excess of 300 kd and exhibit in vivo activity by recruiting neutrophils into rabbit skin. The absence of immune cell-derived chemoattractants such as interleukin-1 and leukotriene B4 in these coronary sinus effluents suggests that the observed chemotactic activity is cardiac derived. Results of this investigation therefore demonstrate the release of neutrophil chemotactic factors by ischemic human hearts during cardiopulmonary bypass.


Localisation of human speech by the newborn baby and the effects of pethidine ('meperidine').
Eight newborn babies were tested to see whether they could make discriminating headturn responses to the sound of a 9-second recording of a human voice coming from 15 degrees, 30 degrees and 80 degrees from the midline, from either the right or left side. The babies showed significant differences in response to sounds coming from the right and the left, and to sounds coming from 15 degrees and 80 degrees from the midline. Pethidine ('Meperidine') given to the mother during labour had a significant effect, both on degree of response and on the babies' apparent ability to localize sound.


The problems of surgical treatment for cardiac myxoma and associated lesions.
Twenty-four patients with cardiac myxomas consisting of 22 left and 2 right atrial myxomas were operated on. All myxomas were removed with an excision of the attachment walls using a cardiopulmonary bypass. Two myxomas required a partial cardiopulmonary bypass from the femoral vein to the artery prior to operation because they were on the verge of becoming stuck in the atrioventricular valves and potentially causing shock. For embolic complications of myxoma, the embolus of the external carotid artery was extirpated before undergoing cardiac surgery. In a patient with pulmonary infarction, the infarcted lung was resected simultaneously. Another patient with a cerebral infarction received a clipping of an aneurysm which later appeared in the infarcted area. For associated cardiac lesions, two patients underwent a coronary artery bypass graft and one mitral valve replacement with tricuspid annuloplasty. In the former two cases, the myxoma was removed prior to coronary artery bypass grafting because the use of retrograde coronary perfusion was considered to be sufficient to protect the heart. In the latter case, the removal of the myxoma first disclosed a significant mitral lesion which had been masked by the huge myxoma. All patients but one, who died of pneumonia, showed a good recovery. In this series, the problems of surgical treatment for cardiac myxoma and associated lesions are also discussed.


Determinants of broadband access and affordability: An analysis of a community survey on the digital divide.
Broadband access in the home is a necessity, especially since the COVID-19 pandemic. Increasingly, connectivity is of vital importance for school, work, family, and friends. Existing international research on the implementation of broadband has studied its adoption patterns with a focus on the rural/urban digital divide. This paper explores the digital divide in a case study of the seventh largest city, by population, in the United States; San Antonio is a majority-minority city where over half of the people are Hispanic. This paper focuses on the five key affordability factors that drive broadband adoption. Researchers test social exclusion theory, the structural facets of poverty and social marginality to ascertain its potential impact on broadband access. The authors conducted a survey in both English and Spanish to learn more about the affordability factors that influence the broadband digital divide. Through our analysis, we found evidence that four of the factors (geographical disparities, profit-based discrimination, technology deployment cost, and socio-economic factors) played a role in the digital divide in this case study. The results of this study demonstrate that the digital divide is not exclusively a rural/urban digital divide, but can also occur in an intra-city context. This is especially evident in low-income areas within the city because they have substantially lower broadband adoption rates. The results of this study demonstrate the importance of looking closely at issues of social exclusion of marginalized groups and the affordability of broadband access intra-city.


Metabolic profiling of chickpea-Fusarium interaction identifies differential modulation of disease resistance pathways.
Chickpea is the third most widely grown legume in the world and mainly used as a vegetarian source of human dietary protein. Fusarium wilt, caused by Fusarium oxysporum f. sp. ciceri (Foc), is one of the major threats to global chickpea production. Host resistance is the best way to protect crops from diseases; however, in spite of using various approaches, the mechanism of Foc resistance in chickpea remains largely obscure. In the present study, non-targeted metabolic profiling at several time points of resistant and susceptible chickpea cultivars using high-resolution liquid chromatography-mass spectrometry was applied to better understand the mechanistic basis of wilt resistance or susceptibility. Multivariate analysis of the data (OPLS-DA) revealed discriminating metabolites in chickpea root tissue after Foc inoculation such as flavonoids, isoflavonoids, alkaloids, amino acids and sugars. Foc inoculated resistant plants had more flavonoids and isoflavonoids along with their malonyl conjugates. Many antifungal metabolites that were induced after Foc infection viz., aurantion-obstine β-glucosides and querecitin were elevated in resistant cultivar. Overall, diverse genetic and biochemical mechanisms were operational in the resistant cultivar for Foc defense as compared to the susceptible plant. The resistant chickpea plants employed the above-mentioned metabolic pathways as potential defense strategy against Foc.


Differences in sarcolemmal preparations: cell surface material and membrane sidedness.
Two different procedures were employed for the isolation of sarcolemma from the rat heart and the membranes were studied with respect to the presence of cell surface material as well as their functional characteristics. Both hypotonic shock-LiBr treatment method (fraction HL) and sucrose density gradient method (fraction S) yielded membranes enriched 8 to 13 fold with respect to Na+-K+ ATPase and adenylate cyclase activities in comparison to heart homogenate. Cell surface material was demonstrated on the outer surface of the vesicles only in fraction HL with cationic dyes, lanthanum and ferritin, applied either to the isolated fractions or perfused in the heart through coronaries. Fraction HL also had high sialic acid content. ATP independent Ca2+ binding in fraction HL was about 6 times more than that in fraction S which had little sialic acid and showed no cell surface staining with cationic dyes. On the other hand, ATP-dependent Ca2+ binding and Ca2+-stimulated Mg2+ dependent ATPase activities in fraction S were 4 to 6 times higher than those in fraction HL. Epinephrine stimulated adenylate cyclase in fractions HL and S by 24 and 3% whereas ouabain was found to inhibit Na+-K+ ATPase in these fractions by 80 and 10% respectively. A mild treatment of the membranes with deoxycholate to eliminate the semipermeable characteristics or effects of sidedness of the vesicles resulted in an almost complete ouabain inhibition of Na+-K+ ATPase in both fractions. These data suggest that presence of cell surface material as well as membrane sidedness has an important role in in vitro expression of functional characteristics of sarcolemma. It is emphasized that sarcolemmal preparations containing cell surface material will provide information more realistic to the native conditions in situ.


The effect of glutathion on the reaction of cis-and trans-diamminedichloroplatinum(II) with DNA.
Differential pulse polarography study was used to investigate the influence of glutathion on cis- and trans-DDP induced alterations of DNA structure. Though the applied concentration of glutathion has no effect on the reaction on DNA with cis-DDP, it greatly modifies the reaction with trans isomer. This may be an important reason for the ineffectiveness of the trans-DDP as an antitumor drug.


Secondary delayed-type hypersensitivity to sheep red blood cells and minor histocompatibility antigens in mice: transfer of memory by recirculating thoracic duct lymphocytes.
Secondary delayed-type hypersensitivity (DTH) in mice to sheep red blood cells (SRBC) and minor histocompatibility (H) antigens is dependent on long-lived memory T cells. In this paper we investigated whether these memory T cells recirculate. It was shown that late phase "immune' thoracic duct lymphocytes (TDL) from mice which were immunized with SRBC or non-H-2-incompatible spleen cells several weeks previously could adoptively transfer secondary DTH to these antigens. Passing the immune TDL through intermediate recipients demonstrated that these SRBC- or minor H-antigen-reactive memory T cells recirculate from blood to lymph. In contrast to mice immunized with minor H antigens, no secondary type DTH reactivity could be demonstrated in mice immunized with H-2-incompatible spleen cells. Also, after adoptive transfer of TDL from mice immunized with H-2-alloantigens, it was impossible to demonstrate an accelerated DTH reactivity.


Testing the three-pool white matter model adapted for use with T2 relaxometry.
A three-pool model was used to improve white-matter T2 relaxometry in low signal-to-noise (SNR) data. To verify the model very high SNR T2 relaxometry experiments were performed on myelinated tissue samples and three-pool fractions were consistently found. Relaxation curves based on the in vitro results were simulated with multiple SNRs and fit using the three-pool model and three less constraining nonnegative least squares-based methods. All methods performed well with noiseless data. At lower SNR values the three-pool model was superior, primarily due to the fact that the other methods often could not unambiguously calculate pool fractions.


I will always be with you: traditional and complementary therapists' perspectives on patient-therapist-doctor communication regarding treatment of Arab patients with cancer in Israel.
In 2008, an Integrative Oncology Program was implemented at the Clalit Oncology Service in Haifa, Israel, to promote patients' well-being during chemotherapy and advanced stages of disease. We hypothesized that studying the perceptions of Arab complementary and alternative medicine (CAM) therapists would facilitate development of a cross-culturally integrative oncology approach. Semi-structured interviews were held with 27 Arab therapists who use medicinal herbs, the Quran and various CAM modalities, with the aim of characterizing their treatment practices and learning about their perspectives regarding conventional cancer care. Thematic analysis revealed that therapists act as go-betweens, mediating between patients and conventional physicians. Therapists translate diagnoses into Arabic and elucidate key concepts. They tend to perceive their role as gatekeepers accompanying patients through the conventional health system, referring them for further examinations, and providing CAM-based supportive care consultation. CAM therapists have an essential role in supportive care of Arab patients with cancer. Triangular patient-therapist-oncologist communication may have an impact on patients' experience and treatment quality. Recognition of CAM therapists as mediators between patients' health beliefs and conventional perceptions of care may improve doctor-patient dialogue and facilitate supportive care provision in a cross-cultural context.


Dual-target inhibitors of PARP1 in cancer therapy: A drug discovery perspective.
Poly (ADP-ribose) polymerase 1 (PARP1), a key enzyme in DNA repair, has emerged as a promising anticancer druggable target. An increasing number of PARP1 inhibitors have been discovered to treat cancer, most notably those characterized by BRCA1/2 mutations. Although PARP1 inhibitors have achieved great clinical success, their cytotoxicity, development of drug resistance, and restriction of indication have weakened their clinical therapeutic effects. To address these issues, dual PARP1 inhibitors have been documented as a promising strategy. Here, we review recent progress in the development of dual PARP1 inhibitors, summarize the different designs of dual-target inhibitors, and introduce their antitumor pharmacology, shedding light on the discovery of dual PARP1 inhibitors for cancer treatment.


Is robot-assisted retroperitoneal adrenalectomy safe? An investigation of perioperative hypertensive crisis among hypertensive and normotensive patients.
Objective: We examined the incidence of perioperative hypertensive crisis in robot-assisted retroperitoneal laparoscopic adrenalectomy. A consecutive series of 120 patients with adrenal tumours undergoing robot-assisted retroperitoneal laparoscopic adrenalectomy were included. Patients were divided into two groups: group A (hypertension group, 58 cases, mean age 43.59 years) and group B (normotension group, 62 cases, mean age 48.01 years). General anaesthesia was applied using endotracheal intubation and haemodynamic changes were closely monitored. A total of nine (7.5%) hypertensive crisis cases were observed. After intravenous infusion of sodium nitroprusside, seven cases of them were quickly controlled and two cases experienced transient severe hypertension. The incidence of hypertensive crisis was 13.7% and 1.6% in groups A and B, respectively (p < 0.05). These findings highlight the importance of strengthening the monitoring of anaesthesia and taking various measures to effectively control the blood pressure in robot-assisted retroperitoneal laparoscopic adrenalectomy, especially among hypertensive patients.


Cocaine exposure during pregnancy: improving assessment with radioimmunoassay of maternal hair.
To compare radioimmunoassay of postpartum maternal hair samples with a structured maternal interview for the detection of cocaine use during pregnancy. Radioimmunoassay of hair samples obtained postpartum was compared with self-report of cocaine use obtained by confidential, structured interviews of 405 postpartum women. Cocaine or benzoylecgonine was detected in the hair samples of 129 of the 148 women (87%) who reported using cocaine at least once during pregnancy. Thirty-six of 257 women (14%) who reported that they had used no cocaine during pregnancy had positive hair tests. Positive hair assay with negative self-report was significantly more common among women who were unmarried (P = .001), African-American (P < .001), and multiparous (P = .035). Hair analysis is a valuable complement to maternal self-report by interview. The methods used together provide a useful clinical and research technique yielding a comprehensive estimate of gestational cocaine exposure. Either method alone may result in misclassification of gestational cocaine exposure.


Cytomorphology of ovarian clear cell carcinomas in peritoneal effusions.
To investigate and describe the cytomorphology of malignant effusions from ovarian clear cell carcinomas (OCCC). Five cases of malignant peritoneal effusions from OCCC histologically confirmed were analysed and compared. Among the malignant peritoneal effusions exhibiting clear cell features, a characteristic feature of OCCC was the presence of large deposits of a hyaline matrix. This matrix may be typically arranged either in 'raspberry bodies' or 'globule-like' structures. Other rare neoplasms composed of clear cells must be considered in the differential diagnosis such as yolk sac tumour of the ovary, clear cell subtype of endometrial carcinoma and, less frequently, malignant peritoneal mesothelioma as well as metastatic renal cell carcinoma. Ovarian clear cell carcinomas have distinct morphological features that are helpful in making a cytological diagnosis of this entity. The role of cytological examination in ovarian neoplasms is of paramount importance, as stated by The International Federation of Gynecology and Obstetrics (FIGO) recommendations.


Acrylamide: its metabolism, developmental and reproductive effects, genotoxicity, and carcinogenicity.
Monomeric acrylamide is an important industrial chemical primarily used in the production of polymers and copolymers. It is also used for producing grouts and soil stabilizers. Acrylamide's neurotoxic properties have been well documented. This review will focus on pertinent information concerning other, non-neurotoxic, effects observed after exposure to acrylamide, including: its genotoxic, carcinogenic, reproductive, and developmental effects. It will also cover its absorption, metabolism, and distribution. The data show that acrylamide is capable of inducing genotoxic, carcinogenic, developmental, and reproductive effects in tested organisms. Thus, acrylamide may pose more than a neurotoxic health hazard to exposed humans. Acrylamide is a small organic molecule with very high water solubility. These properties probably facilitate its rapid absorption and distribution throughout the body. After absorption, acrylamide is rapidly metabolized, primarily by glutathione conjugation, and the majority of applied material is excreted within 24 h. Preferential bioconcentration of acrylamide and/or its metabolites is not observed although it appears to persist in tests and skin. Acrylamide can bind to DNA, presumably via a Michael addition-type reaction, which has implications for its genotoxic and carcinogenic potential. The available evidence suggests that acrylamide does not produce detectable gene mutations, but that the major concern for its genotoxicity is its clastogenic activity. This clastogenic activity has been observed in germinal tissues which suggest the possible heritability of acrylamide-induced DNA alterations. Since there is 'sufficient evidence' of carcinogenicity in experimental animals as outlined under the U.S. EPA proposed guidelines for carcinogen risk assessment, acrylamide should be categorized as a 'B2' carcinogen and therefore be considered a 'probable human carcinogen.' The very limited human epidemiological data do not provide sufficient evidence to enable one to judge the actual carcinogenic risk to humans. Acrylamide is able to cross the placenta, reach significant concentrations in the conceptus and produce direct developmental and post-natal effects in rodent offspring. It appears that acrylamide may produce neurotoxic effects in neonates from exposures not overtly toxic to the mothers. Acrylamide has an adverse effect on reproduction as evidenced by dominant lethal effects, degeneration of testicular epithelial tissue, and sperm-head abnormalities.


The effect of a chlorhexidine-fluoride varnish on mutans streptococci counts and laser fluorescence readings in occlusal fissures of permanent teeth: A split-mouth study.
To evaluate the effect of a new chlorhexidine-fluoride varnish on mutans streptococci (MS) counts and laser fluorescence (LF) readings in fissures of permanent molars. The study group consisted of 57 healthy schoolchildren (7 to 14 yrs) that volunteered after informed consent. A double-blind split-mouth design was employed and 87 pairs of non-cavitated permanent molars were randomly assigned to treatments with either chlorhexidine-fluoride varnish (CHX-F) or chlorhexidine-thymol varnish (CHX-T, Cervitec Plus) as active control. The varnishes were topically applied at baseline and every sixth week throughout the 24-week study period. Endpoints were MS counts (CRT test) and occlusal LF readings (DIAGNOdent pen) registered regularly during follow-up. At baseline, > 50% of the occlusal fissures harbored high MS counts (≥ 105 CFU), but a significant decrease (P < .05) was found after treatment with both varnishes. After 24 weeks, less than 5% exhibited high counts. There were no significant differences between the varnishes at any time point. The mean LF values were similar in both treatment groups at baseline, but a significant reduction (P < .05) was scored in the CHX-F group after 12 and 24 weeks. A similar reduction was found also in the CHX-T group after 24 weeks. No adverse events were reported. There were no significant differences between the CHX-F and CHX-T varnishes in terms of MS suppression after four applications over 24 weeks. Both varnishes also reduced the LF readings significantly compared with baseline, but further long-term studies are needed to confirm a caries-preventive effect.


Increasing incidence of eosinophilic esophagitis in Sweden: a nationwide population study.
Eosinophilic esophagitis (EoE) is a chronic inflammatory condition of the esophagus associated with dysphagia and esophageal fibrosis. The incidence of EoE is not precisely known, and significant heterogeneity in study design and disease definition have led to widely variable estimates. Through the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study we performed a nationwide population-based study to estimate the incidence and temporal patterns of biopsy-verified EoE. Between October 2015 and April 2017, we contacted all pathology departments in Sweden (n = 28) to obtain biopsy report data on EoE. To assure a high degree of completeness, we restricted the study to 2004-2015. We then calculated age-specific and age-standardized incidence rates. We identified 1412 incident EoE cases between 2004-2015. The overall age-standardized incidence rates of EoE in Sweden was 1.22 per 100,000 person-years. During the study period, there was a significant increase of 33% [95%CI = 31-36%] (P < 0.001) per year in EoE incidence, and in the last 3 years of follow-up (2013-2015) the incidence was 2.79 per 100,000 person-years. This corresponds to a lifetime risk of biopsy-verified EoE for men of 0.33% (1 in 295 men) and for women 0.12% (1 in 813 women). We observed an early peak of EoE disgnosed at age 15-19 years for both males and females, and a second peak in the late 30 s for males, and early 40 s for females. We noted a 3:1 male-to-female predominance, which did not significantly vary over time. EoE seems to be increasing in Sweden, with an overall age-standardized incidence of EoE of 1.22 per 100,000 person-years in the last decade.


Independence of blood pressure and locomotor hyperactivity in normotensive and genetically hypertensive rat.
The spontaneously hypertensive rat (SHR) exhibits locomotor hyperactivity in comparison to its normotensive progenitor Wistar-Kyoto (WKY) strain. We asked whether the hyperactive behavior was a direct consequence of elevated blood pressure in the hypertensive rat. Three experimental protocols were used to chronically alter blood pressure. In the first protocol, a group of adult SHRs was given hydralazine (20 mg/kg/day) in their drinking water to lower blood pressure. These animals exhibited a significant decrease in blood pressure, but no change in locomotor activity. In the second protocol, young SHRs (4 weeks of age) were treated with the same dosage of hydralazine until 16 weeks of age. Blood pressure was significantly decreased in these animals with no change in locomotor activity. In the third protocol, normotensive WKY and Sprague-Dawley (SD) rats were made hypertensive with unilateral renal clips. The resulting increase in blood pressure in these animals did not alter locomotor activity. These results suggest that locomotor hyperactivity is an inherent property of the SHR and is independent of blood pressure.


Estimation of flow in aortocoronary grafts with a pulsed ultrasound Doppler meter.
A newly developed pulsed ultrasound Doppler meter was used for measurement of blood flow in aortocoronary vein grafts during operation. The results were compared with measurements obtained with conventional electromagnetic flowmetry. In 27 grafts, excellent agreement was found between electromagnetic flow probes thoroughly calibrated for varying hematocrit on fresh veins in vitro, and a clip-on type of Doppler probe (r = 0.86). In vitro calibration showed a close correspondence (r = 0.98) with the Doppler technique with no dependency on hematocrit and no need for zero calibration. The use of a conventional electromagnetic flowmeter showed strong dependency on recent calibration, both for saline and for varying hematocrit. Zero-calibration was necessary for every single graft measurement. The application of ultrasound Doppler meters of high quality together with clip-on probes of proper design proved to be superior to electromagnetic flowmetry for intraoperative blood flow measurements.


Good work ability despite multisite musculoskeletal pain? A study among occupationally active Finns.
Although multisite pain (MSP) often threatens work ability (WA), some of those with MSP retain good WA. Our aim was to identify factors associated with good WA among subjects with MSP. A nationally representative sample (the Health 2000-Study, response rate 87%) comprising 3884 occupationally active Finns aged 30-64 years. Data on WA, musculoskeletal pain, physical and psychosocial working conditions, chronic diseases, lifestyle and domestic situation were gathered by questionnaire, interview and clinical examination. Good current WA compared with the lifetime best was defined as ⩾9 on a 0-10 scale. Musculoskeletal pain in 18 body locations was combined into four sites, and thereafter pain in two or more sites was defined as MSP (N=1351). Poisson regression analysis was used to obtain prevalence rate ratios (PRR). Good WA was reported by 48% of the women and 37% of the men with MSP. In a multivariable model good WA was associated with younger age, female gender, physically non-strenuous work (PRR 1.3, 95% CI 1.1-1.5), low job strain (1.2, 1.0-1.4), high supervisor support (1.2, 1.0-1.4), and not having musculoskeletal diseases (1.3, 1.1-1.5), mental disorders (1.4, 1.1-1.9), daytime tiredness (1.4, 1.2-1.7) or economic troubles (1.5, 1.1-1.9). Age-stratified analyses revealed also associations with high coworker support (1.2, 1.0-1.4) and strenuous leisure-time physical exercise (1.2, 1.0-1.4) in those aged 30-44 and low alcohol consumption (1.8, 1.2-2.6) in the age-group 45-64. Several potentially modifiable factors related to health, work, and lifestyle were associated with good WA among occupationally active subjects with MSP.


Personality in patients with affective disorders and their relatives.
In studies of both patients and high-risk subjects, particular patterns of personality have been found to be associated with affective disorders. Neuroticism and features of the melancholic type of personality seem to be risk factors for depression while premorbid features of the manic type of personality predominate in patients with more manic than depressive episodes. While neuroticism prevails in the majority of mental disorders, the 'affective' personality variants appear to be more specifically associated with affective disorders. Personality features were investigated in 122 recovered patients with affective disorders, 58 first-degree relatives (high-risk subjects (HR)) and in the respective control groups (n=48; n=29). Patients were subdivided into: unipolar depression (melancholic subtype); bipolar II; bipolar I with more depressive episodes and bipolar I with more manic episodes. Personality measures were based on the Biographical Personality Interview (BPI) and the Munich Personality Test (MPT). The melancholic personality type (BPI) decreased from the unipolar depressives to the mainly manic group, while features of the manic type increased. MPT scores failed to discriminate between subgroups of patients. HR were significantly more introverted and had a stronger orientation towards social norms than controls according to the MPT, and showed a tendency towards the melancholic type according to the BPI. The sizes of some groups or subgroups are relatively small. Therefore, they have to be enlarged in the continuation of the study so as to increase the power of the statistical tests and thus to ascertain the robustness of the results. Features of the typus melancholicus seem to be a risk factor for depression. The identification of highly predictive risk factors provides an opportunity for the development of prevention programs.


Neurotoxicants: emerging issues and policy options.
Neurotoxicants are increasingly seen as significant public health hazards, the resolution of which is influenced by science as well as economics, politics, and emotions. Three topical issues are presented to illustrate the application or abuse of scientific data in the political arena and to suggest appropriate responsibilities of scientists beyond the generation of data. The examples include regulation of occupation-related neurotoxic exposure, transfer of neurotoxic pollutants among environmental media, and export of neurotoxic hazards to Third World countries. These examples illustrate the variety of ways in which neurotoxicants impinge on policy questions--from international trade, through ecosystem effects, to personal occupational health and safety.


Congestive heart failure: involvement of perivascular peptides reflecting activity in sympathetic, parasympathetic and afferent fibres.
In controls and in patients suffering from congestive heart failure (CHF) the circulating levels of catecholamines, neuropeptide Y-like immunoreactivity (NPY-LI), vasoactive intestinal peptide-LI (VIP-LI), substance P-LI (SP-LI) and calcitonin generated peptide-LI (CGRP-LI) markers of sympathetic, parasympathetic and sensory nervous systems, respectively, have been examined. There was a significant rise in the levels of noradrenaline, NPY-LI and SP-LI already in moderate CHF (New York Heart Association Stage I and II). In patients with severe CHF (NYHA Stage III and IV) the circulating levels of noradrenaline, adrenaline, NPY-LI and SP-LI were significantly increased. CGRP-LI was not altered, despite the fact that this peptide co-exists in many tissues with SP. There was no change in VIP-LI. The pathophysiological significance of this pattern of reaction of circulating catecholamines and neuropeptides is unclear; however, the rise in SP-LI may be a reaction to counterbalance the vasoconstrictive effects of the activation of the sympatho-adrenal system.


Artery diameter ratio after recanalization in endovascular therapy for acute ischemic stroke: a new predictor of clinical outcomes.
This study aimed to investigate the relationship between the artery diameter ratio (ADR) after recanalization and clinical outcomes. Patients with middle cerebral artery occlusion confirmed by DSA from 1 January 2018, to 31 December 2019, were retrospectively analyzed. All patients confirmed TICI grade 2b or 3. The ADR was calculated as M2 segment diameter/M1 segment diameter. Multivariate regression analysis was used to describe clinical outcomes of two groups (ADR < 0.6 and ≥ 0.6). ROC curves were used to compare different models and find the best cutoff. A total of 143 patients were included in the study, including 77 males and 66 females, with an average age of 67.79 ± 12 years. The NIHSS at discharge was significantly higher in the ADR < 0.6 group than another group (mean, 16.37 vs. 6.19, P < 0.001). At 90 days, the cases of functional independence was significantly less in the ADR < 0.6 group (20.97% vs. 83.95%, OR 0.05, 95% CI 0.02-0.12, P < 0.001). The ADR < 0.6 group had a higher incidence of cerebral edema (P = 0.027) and sICH (P = 0.038). The ADR had the strongest power to distinguish mRS > 2 (AUC = 0.851) and DC (AUC = 0.805), and the best cutoff value are 0.6 (specificity 85.19%, sensitivity 75.81%) and 0.58 (specificity 65.96%, sensitivity 100%), respectively. The low ADR is associated with poor outcomes. The decrease in ADR may be an indirect manifestation of the loss of cerebrovascular autoregulation.


Measurement of bilirubin-albumin binding. I. Comparative analysis of four methods and four human serum albumin preparations.
Four methods for the measurement of bilirubin-albumin binding have been compared. Three of these, the fluorescent dye binding (Direct Yellow 7), Sephadex G-25 column chromatography, and the 2-(4-hydroxyazobenzene)benzoic acid (HBABA) dye binding methods demonstrate significant correlations of measured binding capacities for bilirubin over a range of bilirubin/albumin molar ratios. All three methods concurred in the demonstration that fresh adult human sera had a higher molar albumin binding capacity for bilirubin than the purified human serum albumin preparations. The fluorescent dye binding and Sephadex column methods agreed most closely in defining presumed deficiency in binding capacity. The HBABA dye binding method was less consistent and appeared to measure non-bilirubin binding sites on albumin in addition to bilirubin binding sites. The fourth method, the saturation index, yielded highly variable results as compared with the other methods because of an inherent excessive risk of laboratory error.


The association of breastfeeding duration with later maternal feeding styles in infancy and toddlerhood: a cross-sectional analysis.
Breastfeeding modestly reduces obesity risk, yet the mechanisms are not well understood. The goal of the current research was to evaluate the association of breastfeeding duration with a wide range of maternal feeding approaches in late infancy and toddlerhood. A secondary analysis of cross-sectional data from an ethnically-diverse sample of 154 mothers of infants (aged 7-11 months) and toddlers (aged 12-24 months) was performed. Breastfeeding history was self-reported where 75% of mothers had weaned by the time of the interview. Multiple dimensions of maternal feeding approaches were measured using the Infant Feeding Styles Questionnaire which assesses pressuring, restriction, responsive, laissez-faire, and indulgent approaches to feeding. Analyses were performed separately for infants and toddlers and adjusted for maternal education level, ethnicity, and marital status. Mothers of infants who breastfed for longer durations tended to report greater responsiveness to infant satiety cues (p≤0.01) and reduced pressuring in feeding complementary foods (p<0.05). Mothers of toddlers who breastfed for longer durations tended to report reduced pressuring in feeding complementary foods (p<0.01). These results suggest that breastfeeding may shape maternal feeding approaches related to responsiveness to infant cues as infants enter a period of complementary feeding, even after considering a range of demographic characteristics previously associated with breastfeeding behaviors. That responsiveness to feeding cues was not associated with breastfeeding duration in the toddler sample suggests that some aspects of this association might be isolated to infancy.


Mechanistic investigations via DFT support the cooperative heterobimetallic C-H and O-H bond activation across Ta[double bond, length as m-dash]Ir multiple bonds.
A rare heterobimetallic oxidative addition of X-H (X = C, O) bonds is reported. DFT suggests that steric constraints around the bimetallic core play a critical role to synergistically activate C-H bonds across the two metals and thus explains the exceptional H/D exchange catalytic activity of unhindered surface organometallic Ta/Ir species observed experimentally.


Retinal inputs to the geniculate relay cells in the eastern chipmunk (Tamias sibiricus asiaticus): a comparison between color and non-color sensitive cells.
Single unit recordings were made from the relay cells of the lateral geniculate nucleus in the eastern chipmunk. Of 362 relay cells, 47 cells (13%) were classified as color sensitive and the rest as non-color sensitive cells. Non-color sensitive cells were further classified into 5 subclasses: off-phasic, on-phasic, on-off-phasic, on-tonic and uncommon types. Within the color sensitive cells there were 3 subclasses; blue excited and green inhibited (+B-G), blue inhibited and green excited (-B+G), and blue excited (+B) cells. Retinal afferents to color sensitive relay cells had the following characteristics: ganglion cells of their origin were distributed in the central high density areas of the retina and axonal conduction velocities were in the intermediate range, though they were somewhat slow in +B cells.


ARL8 Relieves SKIP Autoinhibition to Enable Coupling of Lysosomes to Kinesin-1.
Long-range movement of organelles within the cytoplasm relies on coupling to microtubule motors, a process that is often mediated by adaptor proteins. In many cases, this coupling involves organelle- or adaptor-induced activation of the microtubule motors by conformational reversal of an autoinhibited state. Herein, we show that a similar regulatory mechanism operates for an adaptor protein named SKIP (also known as PLEKHM2). SKIP binds to the small guanosine triphosphatase (GTPase) ARL8 on the lysosomal membrane to couple lysosomes to the anterograde microtubule motor kinesin-1. Structure-function analyses of SKIP reveal that the C-terminal region comprising three pleckstrin homology (PH) domains interacts with the N-terminal region comprising ARL8- and kinesin-1-binding sites. This interaction inhibits coupling of lysosomes to kinesin-1 and, consequently, lysosome movement toward the cell periphery. We also find that ARL8 does not just recruit SKIP to the lysosomal membrane but also relieves SKIP autoinhibition, promoting kinesin-1-driven, anterograde lysosome transport. Finally, our analyses show that the largely disordered middle region of SKIP mediates self-association and that this self-association enhances the interaction of SKIP with kinesin-1. These findings indicate that SKIP is not just a passive connector of lysosome-bound ARL8 to kinesin-1 but is itself subject to intra- and inter-molecular interactions that regulate its function. We anticipate that similar organelle- or GTPase-induced conformational changes could regulate the activity of other kinesin adaptors.


Management of an increasing prostate-specific antigen level after negative prostate biopsy.
Patients who have a previously negative biopsy in the setting of clinical suspicion of prostate cancer still have a high risk of harboring significant undiagnosed disease. Various markers such as prostate-specific antigen (PSA) velocity, PSA density, PCA3, and newer markers may aid in repeat biopsy selection. Repeating the same biopsy procedure in such patients does not yield high cancer detection rates. More anteriorly directed transrectal or transperineal biopsies are indicated. Multiparametric magnetic resonance imaging can detect abnormal areas, and lesion-targeted biopsies can improve the cancer detection rate.


A prospective and controlled in vivo study to determine if acute episodes of high glucose concentrations in the extra-embryonic celomic cavity could be related to spontaneous abortion.
In vitro preparations have provided evidence suggesting that acute and chronic exposure to very high glucose concentrations can lead to embryonic demise via disruption of the extra-celomic membranes and yolk sac. In this study, we sought to determine, in vivo, if an acute increase in extra-embryonic fluid glucose concentration could cause spontaneous abortion. We employed a pregnant non-human primate model and ultrasound-guided celocentesis at 38-42 days from conception. In three control animals, partial replacement of the extra-embryonic celomic fluid was performed using normal saline containing 0.6 mg/mL of glucose. In four study animals, the extra-celomic fluid was replaced with a similar solution containing high glucose concentrations. All animals were then followed until delivery. Immediately after celocentesis, the estimated celomic fluid glucose concentration in experimental animals ranged between 5 mg/mL and 83.8 mg/mL (8-140 times the physiologic glucose concentration of 0.6 mg/mL). All animals delivered live newborns at term without congenital abnormalities. These findings suggest that transitory increases in the extra-celomic fluid glucose concentration are not likely to cause a spontaneous abortion detectable with the sample size of our study.


Occupational therapy program development for medical-psychiatry units: a cognitive model.
Occupational therapy programs form an essential component of the overall treatment program on medical psychiatry units for patients with depression, physical debilitation, and cognitive dysfunction. This article outlines theoretical and practical aspects of developing an occupational therapy program for medical-psychiatric inpatients. Emphasis is placed on accurate assessment of cognitive and physical functioning to facilitate stratification of patients into appropriate therapeutic activities that are commensurate with their level of functioning. The theoretical basis and orientation of occupational therapy is also discussed vis-à-vis its relevance to the treatment of patients with concurrent medical and psychiatric illness.


Deletion of equilibrative nucleoside transporter-2 protects against lipopolysaccharide-induced neuroinflammation and blood-brain barrier dysfunction in mice.
Neuroinflammation is a common pathological feature of many brain diseases and is a key mediator of blood-brain barrier (BBB) breakdown and neuropathogenesis. Adenosine is an endogenous immunomodulator, whose brain extracellular level is tightly controlled by equilibrative nucleoside transporters-1 (ENT1) and ENT2. This study was aimed to investigate the role of ENTs in the modulation of neuroinflammation and BBB function. The results showed that mRNA level of Ent2 was significantly more abundant than that of Ent1 in the brain (hippocampus, cerebral cortex, striatum, midbrain, and cerebellum) of wild-type (WT) mice. Ent2-/- mice displayed higher extracellular adenosine level in the hippocampus than their littermate controls. Repeated lipopolysaccharide (LPS) treatment induced microglia activation, astrogliosis and upregulation of proinflammatory cytokines, along with aberrant BBB phenotypes (including reduced tight junction protein expression, pericyte loss, and immunoglobulin G extravasation) and neuronal apoptosis in the hippocampus of WT mice. Notably, Ent2-/- mice displayed significant resistance to LPS-induced neuroinflammation, BBB breakdown, and neurotoxicity. These findings suggest that Ent2 is critical for the modulation of brain adenosine tone and deletion of Ent2 confers protection against LPS-induced neuroinflammation and neurovascular-associated injury.


Single-Cell RNA-seq Analysis of a Human Embryonic Stem Cell to Endothelial Cell System Based on Transcription Factor Overexpression.
Human embryonic stem cell (hESC)-derived endothelial cells (ECs) possess therapeutic potential in many diseases. Cytokine supplementation induction and transcription factor overexpression have become two mainstream methods of hESC-EC induction. Single-cell RNA-seq technology has been widely used to analyse dynamic processes during hESC-EC induction and components of induced endothelial cells. However, studies that used single-cell RNA-seq are mainly based on cytokine supplementation methods. In this study, we used a high-efficiency human embryonic stem cell-endothelial cell line (hESC-EC) called the "FLI1-PKC system" as a research model and employed single-cell RNA sequencing (scRNA-seq) to investigate the transcriptional landscape and cellular dynamics. The high-efficiency hESC-EC induction (FLI1-PKC) system was established in our previous study. We applied single-cell RNA sequencing (scRNA-seq) of the differentiated cells at different time points and investigated the gene expression profiles. The FLI1-PKC induction system can directionally differentiate hESCs into mature endothelial cells with all the requisite functions. Unlike other hES-EC induction protocols, the FLI1-PKC method follows a different induction route; nonetheless, the transcriptome of induced endothelial cells (iECs) remains the same. The elevated number of activated transcription factors may explain why the FLI1-PKC system is more effective than other hES-EC protocols. Our study has presented a single-cell transcriptional overview of a high-efficiency hESC-EC induction system, which can be used as a model and reference for further improvement in other hESC induction systems.


Application of Monte Carlo simulation for carcinogenic and non-carcinogenic risks assessment through multi-exposure pathways of heavy metals of river water and sediment, India.
Heavy metal contamination has severe detrimental impacts on the entire river ecosystem's quality and causes potential risks to human health. An integrated approach comprising deterministic and probabilistic (Monte Carlo simulation) models with sensitivity analysis was adopted to determine heavy metals' chronic daily intake (CDI) and their associated health risks from the riverine ecosystem. Both carcinogenic and non-carcinogenic risks of water and sediment were estimated through multi-exposure pathways. The analytical results indicated that the concentration patterns of heavy metals in sediment (Fe > Mn > Sr > Zn > Cr > Cu > Cd) were slightly different and higher than in water (Fe > Zn > Cr > Sr > Mn > Cu > Cd). The potential carcinogenic risks of Cr and Cd in sediment (5.06E-02, 5.98E-04) were significantly (p < 0.05) higher than in water (9.08E-04, 8.97E-05). Moreover, 95th percentile values of total cancer risk (TCR) for sediment (1.80E-02, 3.37E-02) were about 22 and 143 times higher than those of water (8.10E-04, 2.36E-04) for adults and children, respectively. The analysis of non-carcinogenic risk revealed a significantly higher overall hazard index (OHI) for both sediment (adults: 1.26E+02, children: 1.11E+03) and water (adults: 3.26E+00, children: 9.85E+00) than the USEPA guidelines (OHI ≤ 1). The sensitivity analysis identified that the concentration of heavy metals was the most influencing input factor in health risk assessment. Based on the reasonable maximum exposure estimate (RME), the study will be advantageous for researchers, scientists, policymakers, and regulatory authorities to predict and manage human health risks.


Effect of feeding on reproductive performance in Finnish dairy cows.
The effect of 2 types of feeding on the involution of the genital tract and on the fertility was studied in 79 Finnish dairy cows on a research farm. The cows were fed twice a day with home-produced feed in accordance with the Finnish feeding standard. The cows were divided according to the type of feed into a hay-urea group and a silage group. The cows were examined clinically by rectal palpation 3 times a week during 8 weeks postpartum. The time required for the complete involution of uterus and cervix was recorded. The cows in the silage group had a significantly longer time in uterine involution, a lower fertility rate at first insemination and a longer interval from calving to conception than those in the hay-urea group. The pregnancy rate in the first insemination was in the hay-urea group 91% and in the silage group 57%. The interval between calving and the first insemination was shorter in the hay-urea group than in the silage group: 71.4 +/- 10.6 and 74.0 +/- 10.3 days, respectively. The interval between calving and conception was in the hay-urea group significantly (p less than 0.01) shorter than in the silage group; 74.8 +/- 15.1 and 89.5 +/- 24.4 days, respectively.


Design, synthesis, and evaluation of new 2-oxoquinoline arylaminothiazole derivatives as potential anticancer agents.
A series of novel 2-oxoquinoline derivatives containing arylaminothiazole were designed and synthesized as potential antitumor agents. The synthesized compounds were evaluated for their in vitro cytotoxicity activity against HeLa, NCI-H460, T24 and SKOV3 cancer cell lines using MTT assay. Among them, compound A7 exhibited the most potent activity against the test cancer cell lines, with the IC50 values ranged from 4.4 to 8.7 µM. The results of tubulin polymerization assay showed that compound A7 could inhibit tubulin polymerization in vitro. Meanwhile, molecular docking study revealed that A7 can bind to the colchicine site of tubulin and formed hydrogen bonds with key amino acid residues in the active site. Further mechanism study demonstrated that compound A7 blocked cell cycle arrest at G2/M phase, induced cell apoptosis and depolarized mitochondria of HeLa cells. Collectively, our findings suggest that A7 could serve as a promising lead for the development of more efficient microtubule polymerization inhibitors for cancer therapy.


The evolving role of acute stroke imaging in intravenous thrombolytic therapy: patient selection and outcomes assessment.
In early trials of thrombolysis, unenhanced CT was used to exclude patients with brain hemorrhage or large infarctions but was insensitive to stroke pathophysiology or early signs of cerebral ischemia or infarction. Currently, CT angiography, CT perfusion, and MR imaging can provide information about stroke mechanisms and prognosis, quantify penumbral tissue, and support risk stratification and patient selection. This article reviews the role of neuroimaging in the original intravenous thrombolytic trials, current application of these technologies, and the potential future role of imaging to extend the time window for thrombolysis and to augment therapeutic success.


Diabetes mellitus among outpatients with COPD attending a university hospital.
Type 2 diabetes mellitus is a common comorbidity of COPD, but there are still many doubts about the relation among diabetes and COPD. We retrospectively collected data from patients afferent to our Respiratory Diseases outpatient clinic at the Tor Vergata University Hospital between 2010 and 2012. The study population was analyzed by clusters of age, gender, body mass index (BMI), smoking status, lung function, concomitant pharmacologic therapies and comorbidities. The values of the association between variables were expressed as odds ratio. Data were adjusted for gender, age and possible confounding variables by Mantel-Haenszel method. We identified 493 patients with COPD. Ninety-two (18.7 %) patients were affected by type 2 diabetes mellitus, with no significant gender differences. The prevalence distribution was similar among the different age clusters, but the association was stronger in patients younger than 65 years. The association was present only in obese subjects in whom it was significant only in patients with moderate-to-severe COPD, but not mild COPD. The presence of cardiovascular diseases was significantly associated with diabetes mellitus in patients with COPD. There was a slight association of inhaled corticosteroid (ICS) use with the presence of diabetes mellitus in COPD, but the combination of an ICS with a β2-agonist apparently reduced this association. The association with type 2 diabetes mellitus was greater in patients with COPD respect to general population, and correlated with the increase in BMI and the presence of other comorbidities, suggesting that both diseases may be targets of systemic inflammation.


Approaches for improving the toileting problems of hemiplegic stroke patients with poor standing balance.
[Purpose] Our objective was to evaluate the residual dynamic and static functionality in the sitting position of hemiplegic stroke patients who require help to pull their lower garments up and down during toileting. [Subjects and Methods] The subjects were 11 hemiplegic patients. We gathered data on the patients' motor paralysis, sensory capacity, lower extremity muscle strength, trunk control, ability to roll and sit up from a lying position, sitting balance, and ability to pull the lower garments up and down. We then compared 2 groups: those able to pull the lower garments up and down independently while standing (the "independent group"), and those who were unable to do so (the "non-independent group"). [Results] Though the non-independent group had severely and significantly reduced trunk control and abilities as a whole, there was no significant difference from the independent group in static and dynamic sitting balance. [Conclusion] We conclude that, to enable hemiplegic patients with poor standing balance to pull their lower garments up and down, it is necessary to do these maneuvers in a sitting, rather than a standing, position, or to develop garments that are easier to put on and take off.


Increased Phosphaturia Accelerates The Decline in Renal Function: A Search for Mechanisms.
In chronic kidney disease (CKD), high serum phosphate concentration is associated with cardiovascular disease and deterioration in renal function. In early CKD, the serum phosphate concentration is normal due to increased fractional excretion of phosphate. Our premise was that high phosphate intake even in patients with early CKD would result in an excessive load of phosphate causing tubular injury and accelerating renal function deterioration. In CKD 2-3 patients, we evaluated whether increased phosphaturia accelerates CKD progression. To have a uniform group of patients with early CKD, 95 patients with metabolic syndrome without overt proteinuria were followed for 2.7 ± 1.6 years. The median decline in eGFR was 0.50 ml/min/1.73 m2/year. Patients with a more rapid decrease in eGFR had greater phosphaturia. Moreover, the rate of decrease in eGFR inversely correlated with the degree of phosphaturia. Additionally, phosphaturia independently predicted renal function deterioration. In heminephrectomized rats, a high phosphate diet increased phosphaturia resulting in renal tubular damage associated with inflammation, oxidative stress and low klotho expression. Moreover, in rats with hyperphosphatemia and metabolic syndrome antioxidant treatment resulted in attenuation of renal lesions. In HEK-293 cells, high phosphate promoted oxidative stress while melatonin administration reduced ROS generation. Our findings suggest that phosphate loading in early CKD, results in renal damage and a more rapid decrease in renal function due to renal tubular injury.


Mydriasis from Datura wrightii.
A 4-year-old girl had painless, uniocular mydriasis after picking flowers. Pharmacologic testing with 1% pilocarpine confirmed the probability that an atropine-like agent had been instilled in the affected eye. The flowers were identified as Datura wrightii and contained scopolamine, hyoscyamine, and atropine on thin-layer chromatography.


When BAT is lacking, WAT steps up.
Brown adipose tissue (BAT) has evolved to generate heat to maintain core body temperature, but it is also of great importance for the regulation of energy balance. In addition to BAT, mammals can induce the formation of "brown adipocyte-like" or "beige" fat cells in white adipose tissue and understanding their regulation could have implications for the treatment of metabolic diseases.


Characterization of antigenic determinants on human solubilized apolipoprotein B. Conformational requirements for lipids.
The expression of low density lipoprotein (LDL) antigenic determinants in the delipidated and solubilized apolipoprotein B (apo-B) free of sodium dodecyl sulfate (SDS) has been studied. Of the six distinct determinants which react with previously characterized monoclonal antibodies against LDL (Milne, R.W., Theolis , R., Jr., Verdery , R.B., and Marcel , Y.L. (1983) Arteriosclerosis 3, 23-30), only one, that recognized by antibody 1D1 , was expressed on the soluble apo-B, indicating that soluble apo-B may be partly denatured. The average immunoreactivity of apo-B with antibody 1D1 was similar to or lower than that of intact LDL (mean 36%, range 93-20%). Therefore, delipidation and solubilization did not expose on apo-B any additional site reactive with 1D1 . When apo-B was equilibrated with either SDS micelles or with cholesterol-lecithin liposomes, the immunoreactivity of the determinant recognized by antibody 2D8 was partially regenerated, but not that of the others. In contrast, incubation of apo-B with microemulsions containing a hydrophobic core of cholesteryl esters also restored the antigenicity of the determinants reacting with antibodies 3F5 , 4G3 , and 5E11 . However, the regeneration of these antigenic determinants could only be achieved when solubilized apo-B was treated with SDS prior to equilibration with microemulsion preparations. In conclusion, three types of antigenic determinants have been identified on apo-B. The first type, such as that recognized by antibody 1D1 , is expressed both on LDL and on apo-B and is constituted by the primary and secondary structure of apo-B. The second type, an example being that recognized by 2D8 , is a conformational determinant which requires the presence of amphipathic lipids such as lecithin and cholesterol or SDS micelles. The third type, which reacts with antibodies 3F5 , 4G3 , and 5E11 , represents different conformational determinants which require the association of apo-B with lipid structures having a cholesteryl ester hydrophobic core. It may be significant that the latter determinants are those close to the LDL receptor-binding site on apo-B and that this domain of apo-B has a complex tertiary and quaternary structure as evidenced by the conformational requirements of the antigenic determinants.


Interspecies spread of Staphylococcus aureus clones among companion animals and human close contacts in a veterinary teaching hospital. A cross-sectional study in Greece.
Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) prevalence among companion animals and veterinary personnel (VP) was investigated. Strains' molecular characteristics were evaluated in order to assess S. aureus transmission. Specimens (224) from colonized and infected sites of 102 animals (92 dogs, 10 cats) and 18 VP were collected during 2012 and 2013. Antibiotic susceptibility was performed by the disk diffusion method and Etest. mecA, mecC, tst (toxic shock syndrome toxin) and lukF/lukS-PV (Panton-Valentine leukocidin, PVL) genes were investigated by PCR. Genotypes were identified by Multi Locus Sequence Typing (MLST), Staphylococcal Cassette Chromosome mec (SCCmec), accessory gene regulator group (agr), spa and Pulsed Field Gel Electrophoresis (PFGE). S. aureus prevalence among pets and VP was 36.3% (37/102) and 38.9% (7/18), respectively. Younger companion animals, those living in rural areas, having a disease upon admission or Coagulase-negative staphylococci co-carriage showed significantly higher prevalence of S. aureus isolation (p<0.05). Twenty-six pets and five VP carried PVL-positive S. aureus. In total, 60 S. aureus strains were recovered (53 from pets, seven from VP) of which 16 were MRSA (26.7%), 12 mecA- and four mecC-positive. MRSA showed higher resistance rates against other antimicrobials as compared to methicillin-susceptible ones. Strains were classified by MLST in 13 STs, with the predominance of ST80 and ST15. In MRSA, SCCmec types II, IV and XI were identified. The most frequent spa types were t5559 and t7558. Fifty-six strains were classified into 15 PFGE types. Comparison of genetic markers shows that identical or very similar strains disseminate among animals and VP. Companion animals harbor PVL-positive clones constituting a possible source for transmission to humans.


Complication of Clorpactin WCS90 therapy for interstitial cystitis.
A case of ureteral fibrosis complicating Clorpactin WCS90 treatment for interstitial cystitis in a patient with vesicoureteral reflux is presented. The results of a laboratory experiment designed to study the effects of Clorpactin WCS90 on refluxing ureters are discussed.


Football injuries in children and adolescent players: are there clues for prevention?
Football (soccer) is the world's most popular sport with most players being younger than 18 years. Playing football can induce beneficial health effects, but there is also a high risk of injury. Therefore, it is necessary to implement measures for preventing injuries. The present review analyzes and summarizes published scientific information on the incidence and characteristics of football injuries in children and adolescent players to arrive at sound conclusions and valid considerations for the development of injury-prevention programs. A literature search was conducted up to November 2012. Fifty-three relevant scientific publications were detected. Thirty-two studies fulfilled the inclusion criteria for pooled analysis. Additional information from the remaining 21 studies was considered where appropriate to obtain a broader perspective on the injury problem in children and youth football. Training injury incidence was nearly constant for players aged 13-19 years, ranging from 1 to 5 injuries per 1,000 h training. Match injury incidence tended to increase with age through all age groups, with an average incidence of about 15 to 20 injuries per 1,000 match hours in players older than 15 years. Between 60 and 90 % of all football injuries were classified as traumatic and about 10-40 % were overuse injuries. Most injuries (60-90 %) were located at the lower extremities with the ankle, knee, and thigh being mostly affected. The frequency of upper-extremity and head/face injuries was higher in those studies that analyzed match injuries only. The most common injury types were strains, sprains, and contusions (10 up to 40 % each). There is some evidence that the risk of traumatic injuries and, in particular, of sustaining a fracture, contusion, or concussion was higher during match play than in practice sessions. Fractures were more frequent in children younger than 15 years than in older players. About half of all time-loss injuries led to an absence from sport of less than 1 week, one third resulted in an absence between 1 and 4 weeks, and 10 to 15 % of all injuries were severe. Separate data for players under the age of 11 years are almost absent. Maturation status seems to have an influence on injury characteristics, although evidence is not conclusive at this time. Three main areas seem to be of particular relevance for future prevention research in young football players: (1) the substantial number of severe contact injuries during matches, (2) the high number of fractures in younger players, and (3) the influence of maturation status and growth spurts.


Fatal air embolism as a complication of laser-induced hyperthermia.
Laser-induced hyperthermia is a new treatment modality for malignancies. When large tumors are treated with laser thermia, relatively high laser powers (4-6 W) must be used to accomplish destruction of the cancerous cells. Overheating and burning of the laser fibers and contact tips during laser thermia treatment must be prevented by using coaxial gas or fluid flow. The present report describes a case of fatal air embolism as a complication of laser thermia using coaxial gas. The authors warn all surgeons performing this procedure not to use coaxial air flow for cooling the contact tips because of the potential risk of air embolism.


The influences of the COVID-19 pandemic on medical service behaviors.
The outbreak of the novel coronavirus (COVID-19) has greatly impacted medical services worldwide. In addition to changing the processes used by hospital medical services, it has also changed the behaviors of medical staff, resulting in a completely different appearance. Fear of being infected with COVID-19 makes patients fear entering hospitals, and hospitals must repeatedly screen patients prior to entry in order to confirm that they are not infected. Patients are then separated according to their symptoms and travel, occupation, contact and cluster histories (TOCC), which seriously affects them. In addition, hospitals have invested a lot of money into the whole visiting process and into the equipment required to prevent the spread or lessen the impact of COVID-19.


Mediators of the association of major depressive syndrome and anxiety syndrome with postpartum smoking relapse.
Based on conceptual models of addiction and affect regulation, this study examined the mechanisms linking current major depressive syndrome (MDS) and anxiety syndrome (AS) to postpartum smoking relapse. Data were collected in a randomized clinical trial from 251 women who quit smoking during pregnancy. Simple and multiple mediation models of the relations of MDS and AS with postpartum relapse were examined using linear regression, continuation ratio logit models, and a bootstrapping procedure to test the indirect effects. Both MDS and AS significantly predicted postpartum smoking relapse. After adjusting for MDS, AS significantly predicted relapse. However, after adjusting for AS, MDS no longer predicted relapse. Situationally based self-efficacy, expectancies of controlling negative affect by means other than smoking, and various dimensions of primary and secondary tobacco dependence individually mediated the effect of both MDS and AS on relapse. In multiple mediation models, self-efficacy in negative/affective situations significantly mediated the effect of MDS and AS on relapse. The findings underscore the negative impact of depression and anxiety on postpartum smoking relapse and suggest that the effects of MDS on postpartum relapse may be largely explained by comorbid AS. The current investigation provided mixed support for affect regulation models of addiction. Cognitive and tobacco dependence-related aspects of negative and positive reinforcement significantly mediated the relationship of depression and anxiety with relapse, whereas affect and stress did not. The findings emphasize the unique role of low agency with respect to abstaining from smoking in negative affective situations as a key predictor of postpartum smoking relapse.


[Recent progress in the treatment of Cushing's disease].
Transsphenoidal surgery, possibly through the endoscopic approach, remains the first line treatment. Opposing cortisol action with mifepristone proved efficacious in some individual cases but but with major monitoring difficulties. Combined treatment with three anticortisolic drugs (metyrapone, ketokonazole, O,p'DDD) is particularly attractive in severe cases. The Nelson's syndrome has been revisited, and the corticotroph tumor progression should rather be cautiously assessed after bilateral adrenalectomy. Two molecules potentially act directly to suppress the ACTH secretion by the corticotroph adenoma: agonists of the D2 Dopamine receptor and of the somatostatin receptor type 5. Their efficacy remains modest (20 to 30% of the patients actually normalize urinary cortisol). Pituitary radiotherapy can be efficiently performed by stereotaxic approach.


Does the Use of Social Media Affect Online Health Information-Seeking Behaviors among Underserved African Americans in Rural Alabama?
This study aimed (1) to investigate levels of technology device access and social media use among African Americans in rural Alabama, (2) to examine the prevalence of online health information-seeking behaviors, and (3) to identify associations of technology device access and social media use with online health information-seeking behaviors. A convenience sample of 185 African Americans aged 18 and older was recruited from a rural county in Alabama. Multilinear regression was conducted to examine the associations. Nearly 60% of participants had access to the internet, smartphone, and tablets/computers. The prevalence of online health information-seeking behaviors was low. Technology device access was not associated with online health information-seeking behaviors, while more social networking sites were associated with more online health information-seeking behaviors. Public health interventions are needed to promote internet use for health purposes among rural African Americans. Offline health information services should also target those lacking internet access.


The S-CAHPS Survey in Urology.
The S-CAHPS survey assesses patient experience and satisfaction with 1 episode of surgical care. We describe the initial implementation, results and experience using S-CAHPS in urology. This was a prospective, institutional review board approved, observational study at a tertiary care academic medical center. Adult patients who underwent elective outpatient or 23-hour observation surgery during a 33-month period were mailed the survey. Survey content was separated into composites 1 to 6 and percent top box scoring (percent of most positive responses) was performed. Summary scores for each composite were correlated with the mean of a global surgeon rating question. A total of 430 surveys were returned for a 33.8% response rate. Respondents were statistically older than nonrespondents and more likely to reside in Michigan (p <0.05). Mean ± SD global surgeon rating was 9.50 ± 1.04 on a scale of 0-worst to 10-best surgeon possible. Global surgeon rating correlated most highly with the question composites for "How well surgeon communicates with patients after surgery" (composite 5, τ = 0.459), followed by "Information to help you recover from surgery" (composite 4, τ = 0.400). Conversely, there was lower correlation with composites pertaining to "Information to help you prepare for surgery" (composite 1, τ = 0.251). Survey results suggest that patient satisfaction with the surgeon is more influenced by postoperative communication and information than by preoperative counseling and decision making processes. This underscores the importance of attention to continued postoperative care and interactions. The role of S-CAHPS in urology requires further exploration in this era of quality improvement.


Cadmium impairs the development of natural killer cells and bidirectionally modifies their capacity for cytotoxicity.
Cadmium (Cd) is a highly toxic heavy metal in the environment. The aim of this study was to investigate the impact of Cd on natural killer (NK) cells. C57BL/6 mice were treated with 10 ppm Cd via drinking water for 3 months, and the development of NK cells in the bone marrow (BM) and the cytotoxicity of mature NK (mNK) cells in the peripheral immune organs were evaluated thereafter; the impact of Cd on the cytotoxicity of mNK cells from human peripheral blood mononuclear cells (PBMC) was also investigated. Whereas Cd treatment impaired the differentiation of NK progenitors in the BM, Cd treatment activated the JAK3/STAT5 signaling to drive the proliferation of mNK cells and thereby lead to a compensation increase of mNK cells in the peripheral immune organs of mice. Additionally, Cd treatment bidirectionally regulated the cytotoxicity of mouse mNK cells to differential tumor cells, dependent on the levels of Fas expression in the tumor cells; mechanically, Cd treatment activated the JAK3/STAT5 signaling to promote the expression of FasL in mNK cells to increase their cytotoxicity, while Cd treatment reduced the expression of granzyme B in mNK cells to impair their cytotoxicity in the peripheral immune organs of mice. Likewise, in vitro assays indicated that Cd treatment also activated the JAK3/STAT5 signaling to increase the expression of FasL, whereas Cd treatment reduced the expression of granzyme B in human mNK cells. Thus Cd treatment impaired the development of NK cells in the BM and bidirectionally regulated the cytotoxicity of mNK cells in the peripheral immune organs, which may extend our current understanding for the immunotoxicity of Cd.


Invasive features of superficial oesophageal squamous cell carcinoma-analysis of risk factors for lymph node metastasis.
There are currently no studies that have examined the clinicopathological factors in detail, including the histological images of the invasive front, and the risk of lymph node metastasis (LNM) in superficial oesophageal squamous cell carcinoma (SESCC). This study aimed to develop an algorithm that contributes to a better assessment of the risk of LNM and recurrence in SESCC. Clinicopathological factors, such as submucosal (SM) invasion distance, were examined in 88 surgically resected cases of SESCC. An SM invasion distance of 600 μm was the statistically best customer value for LNM (p = 0.0043). To obtain a histological image of the invasive front, we evaluated modified tumour budding (MBD) by modifying the number of tumour foci constituent cells and foci in tumour budding. We also evaluated the smallest number of tumour foci. Using these factors, we developed an algorithm to predict the risk of LNM. The best algorithm was created using an SM invasion distance of 600 μm and an index of 5 or more foci consisting of five or fewer tumour cells in the MBD (MBD5 high-grade ≥ 5), which was also significantly associated with recurrence-free survival (p = 0.0305). Further study of the algorithm presented in this study is expected to improve the quality of life of patients by selecting appropriate additional treatments after endoscopic resection and appropriate initial treatment for SESCC.


Molecular cloning and functional characterization of multiple ApOSCs from Andrographis paniculata.
Triterpenoids have been described in Andrographis paniculata. Oleanolic acid exhibits high biological activity and is widely used in the clinic, and β-sitosterol not only has good biological activity but also plays an important physiological role in plants. However, analysis of the biosynthetic pathway of triterpenoids in Andrographis paniculata has not been reported. Here, we provide the first report of the isolation and identification of nine 2, 3-oxidosqualene cyclases (ApOSC3 to ApOSC11) from A. paniculata. The results showed that ApOSC4 represented a monofunctional synthase that could convert 2, 3-oxidosqualene to β-amyrin. ApOSC5 as a bifunctional 2, 3-oxidosqualene cyclases, could transfer 2, 3-oxidosqualene to β-amyrin and α-amyrin. ApOSC6 to ApOSC8 composed the multifunctional 2, 3-oxidosqualene cyclases that could convert 2, 3-oxidosqualene to β-amyrin, α-amyrin and one or two undetermined triterpenoids. This study provides a better understanding of the biosynthetic pathway of triterpenoids in A. paniculata, and the discovery of multifunctional 2, 3-oxidosqualene cyclases ApOSC5 to ApOSC8 of the facilitates knowledge of the compounds diversity in A. paniculata.


Effects of green tea contents on the quality and antioxidant properties of textured vegetable protein by extrusion-cooking.
The aim of this study was to evaluate the effects of green tea contents (0, 5, 10, and 15%) on texturization and antioxidant properties of textured vegetable protein (TVP) by using a twin-screw extruder. Extrusion conditions were fixed at 140 °C barrel temperature, 50% moisture content, 100 g/min feed rate, and 200 rpm screw speed. The integrity index, hardness, and cutting strength of TVP significantly (P < 0.05) increased with the increase in green tea levels, while cohesiveness, springiness, water holding capacity, and nitrogen solubility index (NSI) significantly (P < 0.05) decreased. Increasing the amount of green tea resulted in better DPPH radical scavenging activity, higher total phenolic, total flavonoid, catechins, and caffeine contents. The (-)-epigallocatechin gallate, (-)-epicatechin, (-)-epigallocatechin, and (-)-epicatechin gallate contents of TVP significantly (P < 0.05) decreased, compared to that of raw materials. The incorporation of green tea in TVP can negatively affect expansion and NSI while positively affect texturization and antioxidant properties.


Design and optimization of a multiplex anti-influenza peptide immunoassay.
Current flu vaccines are based on killed or attenuated virus vaccines that must be altered each year to include the hemagglutinin and neuraminidase genes from a strain of virus predicted to predominate in the coming year. A vaccine that could protect against multiple strains of influenza A and B would be a major asset in the fight against flu-related mortality and morbidity. To support development of such a vaccine, we have developed a Flu Multiplex Assay based on a Luminex platform to assess serum antibody levels to two conserved peptides derived from influenza A (M2 protein) and influenza B (hemagglutinin protein). The peptides were synthesized with a biotin label and subsequently coupled to two different LumAvidin microspheres. We then tested various sera against both types of peptide in the multiplex assay format. The data show that sera from Rhesus macaques immunized with a single peptide react only with the homologous peptide while Rhesus macaques immunized with both peptides respond well to both peptides. Additionally, we were able to specifically compete reactivity to both peptides. We have tested serial bleeds from 100 pediatric patients at ages ranging from 16 to 56 weeks as well as single bleeds from over 100 healthy adults. No overall trend in titer relative to pediatric age was detected. Both demographics exhibited a minimal response to either the A/M2 or B/HA0 peptides. However, the average titer for the pediatric serum samples was significantly lower than that found in the adult population. The adult population exhibited a higher prevalence of low reactive samples. Assay reagents and parameters have been optimized and the assay is shown to be repeatable and robust. The assay will be used to support clinical vaccine trials of a bivalent peptide vaccine.


HPLC determination of lincomycin in premixes and feedstuffs with solid-phase extraction on HLB OASIS and LC-MS/MS confirmation.
A rapid clean-up procedure based on solid-phase extraction (SPE) and HPLC determination of lincomycin in premixes with UV detection is described. After extraction of lincomycin from premix with extraction solvent the extract is applied to OASIS HLB column treated with methanol and water. Lincomycin is eluted with methanol and effluent is analysed on analytical column (phenyl) using mobile phase consists 0.2% phosphoric acid in water and acetonitrile (875:125, v/v). Detection is performed at 208 nm. Quantitation is carried out using external standard. The mean recovery of lincomycin was 105.0+/-7.3%, in concentration range of 250-750 mg kg(-1), and 99.8+/-3.7%, in concentration range of 10,000-150,000 mg kg(-1). The limit of determination, based on a signal-to-noise ratio of 10:1, was 5.2 mg kg(-1). LC-MS/MS confirmation of lincomycin is also presented. Identification was performed by monitoring two pairs of multiple reaction monitoring ions from the parent ions (m/z 407.2-->126.1 and 407.2-->359.2) at the defined retention time window and by matching of the specific tolerance of relative abundance of major ions as stated in the European Union Commission Decision 2002/657/EC.


Apelin secretion and expression of apelin receptors in 3T3-L1 adipocytes are differentially regulated by angiotensin type 1 and type 2 receptors.
Adipocytes play pivotal roles in regulating metabolism through secretion of a variety of adipokines, which in turn is regulated by other metabolic factors (e.g., insulin). Understanding the regulations of adipokine secretion is important because adipokines are implicated with metabolic disorders, such as, obesity and diabetes mellitus. Here, we investigated the regulatory roles of angiotensin II (AngII) on the secretion of apelin in 3T3-L1 adipocytes, and distinct signaling pathways mediated by AngII receptor type 1 (AT₁) and type 2 (AT₂) were revealed. It was found that activation of AT₁ receptors stimulates apelin secretion in Ca²⁺, protein kinase C, and MAPK kinase dependent ways while activation of AT₂ receptors inhibits apelin secretion through cAMP and cGMP dependent pathways. Furthermore, we demonstrate that the expression of apelin receptor (APJ) is also similarly regulated by AT₁ and AT₂ receptors. Finally, a detailed AngII signaling map is proposed.


The relationship between self-induced water intoxication and severity of psychiatric symptoms.
The purpose of this study was to test a theoretical framework that proposed a relationship between severe psychiatric symptoms and self-induced water intoxication (SIWI) by using reliable and valid measures. Twenty of 28 community-dwelling individuals with severe mental illness (SMI) in the sample exhibited excess fluid consumption as reflected by a mean urine specific gravity of 1.003 mEq/L. The psychometric measures included the Positive and Negative Syndrome Scale (PANSS), the Self Deficit Syndrome Scale (SDSS), and the Spielberger State-trait Anxiety Scale (STAI From X-1). A significant relationship was found at p .01 between severity of psychotic symptoms and severity of SIWI and between severity of SIWI and psychopathology symptoms within the PANSS. Anxiety was higher in those with SIWI before fluid loading compared with those with less excess fluid intake (i.e., USG < 1.010), and anxiety decreased from morning to evening in those with SIWI compared with those who did not exhibit excess fluid intake. The findings revealed a strong relationship between SIWI and severe psychiatric symptoms, including psychosis and a broad range of psychiatric symptoms. The findings provided initial support for the proposed theory, and consideration needs to be given to the development of interventions to augment existing treatment of fluid control.


Allergic Aspergillus flavus rhinosinusitis: a case report from Qatar.
Fungal involvement in rhinosinusitis is classified into four major forms: allergic, mycetoma, chronic invasive (indolent) and acute invasive (fulminant). It can become life threatening if not diagnosed and treated properly. The preliminary diagnosis is usually made by nasal endoscopy and computed tomography (CT) imaging, but tissue biopsy and culture are of vital importance in confirming the disease and in planning treatment. We present a case of allergic fungal rhinosinusitis (AFS) caused by Aspergillus flavus. The clinical manifestation of the disease was the presence of an extensive left nasal polyp. An allergic workup revealed systemic eosinophilia (11.7%), high serum IgE levels (1,201 IU/ml) and a positive skin test for Aspergillus. CT scan showed a total opacification and expansion of the left nasal cavity and sinuses, with a secondary inflammatory reaction on the right side. There was no bony erosion beyond the sinus walls. The patient was operated on using an endoscopic approach (polypectomy and ethmoidectomy), where an abundant amount of allergic fungal mucin and dark crusts were found filling the sinuses. Fungal hyphae were evident in histopathological sections of the removed mucin. Culture of the debris resulted in the growth of Aspergillus flavus. The patient received a full course of systemic and topical steroids. The serum IgE level had dropped to 353 IU/ml and the peripheral eosinophil count to normal (1.38%) by the 10th postoperative month. Surgical debridement and corticosteroids may keep the disease quiescent for a long time.