Evaluation of urinary oxalate levels in patients receiving gastrointestinal lipase inhibitor.
The purpose of this study was to examine the possible effects of a gastrointestinal lipase inhibitor "Orlistat (Xenical)" on the intestinal absorption of oxalate and thereby on the urinary levels of oxalate excretion in overweight patients. Long-term follow-up data of 95 cases (57 men, 38 women; M/W=1.5) were documented. Patients were randomly assigned into two groups. While the patients in group I (n=55) were treated with orlistat (Xenical) for 6 months, patients in group II (n=40) received no specific medication. Calcium, oxalate, and citrate levels were determined in a 24-h urine collection from each patient. To evaluate the significance in the groups as well as the differences between the two groups, ANOVA test was performed and the results were given as mean +/- s.d. Comparative evaluation of urinary oxalate levels during 3-month follow-up clearly showed that urinary oxalate excretion significantly increased in 34/55 patients (61.8%) in the first group (P<0.05). Of these 34 patients, 30 (88.2%) continued to have increased urinary oxalate excretion during 6-month follow-up (P=0.001). However, our data did not show any significant effect of this medication on urinary citrate and calcium levels during 3- and 6-month follow-up evaluation (P=0.05). Our results suggest that increased intestinal absorption of dietary oxalate due to this type of medication in obese patients could make a substantial contribution to urinary oxalate excretion and may increase the risk of stone formation.


Singular diffusionless limits of double-diffusive instabilities in magnetohydrodynamics.
We study local instabilities of a differentially rotating viscous flow of electrically conducting incompressible fluid subject to an external azimuthal magnetic field. In the presence of the magnetic field, the hydrodynamically stable flow can demonstrate non-axisymmetric azimuthal magnetorotational instability (AMRI) both in the diffusionless case and in the double-diffusive case with viscous and ohmic dissipation. Performing stability analysis of amplitude transport equations of short-wavelength approximation, we find that the threshold of the diffusionless AMRI via the Hamilton-Hopf bifurcation is a singular limit of the thresholds of the viscous and resistive AMRI corresponding to the dissipative Hopf bifurcation and manifests itself as the Whitney umbrella singular point. A smooth transition between the two types of instabilities is possible only if the magnetic Prandtl number is equal to unity, Pm=1. At a fixed Pm≠1, the threshold of the double-diffusive AMRI is displaced by finite distance in the parameter space with respect to the diffusionless case even in the zero dissipation limit. The complete neutral stability surface contains three Whitney umbrella singular points and two mutually orthogonal intervals of self-intersection. At these singularities, the double-diffusive system reduces to a marginally stable system which is either Hamiltonian or parity-time-symmetric.


Does prehabilitation modify muscle mass in patients with rectal cancer undergoing neoadjuvant therapy? A subanalysis from the REx randomised controlled trial.
Patients with rectal cancer who present with sarcopenia (low muscle mass) are at significantly greater risk of postoperative complications and reduction in disease-free survival. We performed a subanalysis of a randomised controlled study [the REx trial; www.isrctn.com ; 62859294] to assess the potential of prehabilitation to modify muscle mass in patients having neoadjuvant chemoradiotherapy (NACRT). Patients scheduled for NACRT, then potentially curative surgery (August 2014-March 2016) had baseline physical assessment and psoas muscle mass measurement (total psoas index using computed tomography-based measurements). Participants were randomised to either the intervention (13-17-week telephone-guided graduated walking programme) or control group (standard care). Follow-up testing was performed 1-2 weeks before surgery. The 44 patients had a mean age of 66.8 years (SD 9.6) and were male (64%); white (98%); American Society of Anesthesiologists class 2 (66%); co-morbid (58%); overweight (72%) (body mass index ≥ 25 kg/m2). At baseline, 14% were sarcopenic. At follow-up, 13 (65%) of patients in the prehabilitation group had increased muscle mass versus 7 (35%) that experienced a decrease. Conversely, 16 (67%) controls experienced a decrease in muscle mass and 8 (33%) showed an increase. An adjusted linear regression model estimated a mean treatment difference in Total Psoas Index of 40.2mm2/m2 (95% CI - 3.4 to 83.7) between groups in change from baseline (p = 0.07). Prehabilitation improved muscle mass in patients with rectal cancer who had NACRT. These results need to be explored in a larger trial to determine if the poorer short- and long-term patient outcomes associated with low muscle mass can be minimised by prehabilitation.


Flesh flavor of red swamp crayfish (Procambarus clarkii Girard, 1852) processing by GS-IMS and electronic tongue is changed by dietary animal and plant protein.
The aroma and taste of Procambarus clarkii (Girard, 1852) fed with different dietary protein were investigated by E-tongue and gas chromatography-ion migration spectrometry (GC-IMS) after cooking. The results showed that dietary protein sources had no significant growth performance. Nevertheless, significantly higher richness taste was observed in animal protein group. The inosine-5'-monophosphate content in animal protein group was significantly higher than that in plant protein group. Twelve aldehydes, eleven alcohols, six ketones, three esters, and two acids were identified in the muscle using GC-IMS. 2-Propanol (monomer), 3-octanol (monomer), 3-furanmethanol (dimer), 2-methyl-1-pentanol (monomer), heptanal (monomer), and allylacetic acid (monomer) changed significantly between dietary animal protein and plant protein. These results suggested that dietary plant and animal protein have a similar effect on the growth performance. For the flavor, the crayfish fed with animal protein had higher volatiles and IMP contents, which might contribute to higher richness.


Liposomes with prolonged circulation times: factors affecting uptake by reticuloendothelial and other tissues.
Many of the applications of liposomes drug-delivery systems have been limited by their short circulation half-lives as a result of rapid uptake into the reticuloendothelial (mononuclear phagocyte) system. We have recently described liposomes formulations with long circulation half-lives in mice (Allen, T.M. and Chonn, A. (1987) FEBS Lett. 223, 42-46). A study of the principal factors important to the attainment of liposomes with prolonged circulation half-lives is presented in this manuscript. Liposomes with the longest circulation half-lives, in mice, had compositions which mimicked the outer leaflet of red blood cell membranes (egg phosphatidylcholine/sphingomyelin/cholesterol/ganglioside GM1, molar ratio 1:1:1:0.14). Several other gangliosides and glycolipids were examined, but none could substitute for GM1 in their ability to prolong circulation half-lives. However, other negatively charged lipids with bulky headgroups, i.e., sulfatides and phosphatidylinositol, had some effect in prolonging circulation half-lives, but GM1 was clearly superior in this regard. Bilayer rigidity, imparted by sphingomyelin or other high-phase-transition lipids, acted synergistically with the negatively charged components, especially GM1, in extending circulation times. Circulation half-lives of liposomes increased with decreasing size, but even larger (0.2-0.4 microns) liposomes of the optimum formulations had significantly prolonged half-lives in circulation. Uptake of liposomes into tissues other than liver and spleen increased with increasing circulation times of the liposomes for i.v. and for i.p. injections. Liposomes appeared to move from the circulation into the carcass between 6 and 24 h post-injection. Our ability to achieve significant prolongation in circulation times of liposomes makes possible a number of therapeutic applications of liposomes which, until now, have not been achievable.


Finishing touches: post-translational modification of protein factors involved in mammalian pre-mRNA 3' end formation.
In eukaryotes, a pre-messenger RNA (pre-mRNA) must undergo several processing reactions before it is exported to the cytoplasm for translation. One of these reactions, endonucleolytic 3' cleavage at the polyadenylation site, prepares the pre-mRNA for addition of the poly(A) tail and defines the 3' untranslated region (UTR), which typically contains important gene expression regulatory sequences. While the protein factors responsible for the endonucleolytic cleavage have been largely identified, the means by which their action is limited to the 3' end of the transcription unit and coordinated with other co-transcriptional events remains unclear. In this review, we summarize and review recent findings revealing that the mammalian 3' cleavage factors undergo extensive post-translational modification. These modifications include: arginine methylation, lysine sumoylation, lysine acetylation, and the phosphorylation of serine, threonine and tyrosine residues. Every cleavage factor, though not every subunit, is affected. Human Fip1 and the 59 kDa subunit of cleavage factor I emerge as the most frequently modified core cleavage factor subunits. We outline and compare the various proteomic methods that have uncovered these modifications, and review emerging hypotheses concerning their function. The roles of these covalent but reversible modifications in other systems suggest that 3' end formation in mammals relies upon post-translational modification for proper function and regulation.


Plasminogen activators in vascular remodeling and angiogenesis.
This review considers cellular and molecular mechanisms of the involvement of plasminogen activators in extracellular proteolysis and cell migration and proliferation. The role of plasminogen activators in vascular remodeling in atherosclerosis, restenosis, and angiogenesis is discussed.


The microbial gbu gene cluster links cardiovascular disease risk associated with red meat consumption to microbiota L-carnitine catabolism.
The heightened cardiovascular disease (CVD) risk observed among omnivores is thought to be linked, in part, to gut microbiota-dependent generation of trimethylamine-N-oxide (TMAO) from L-carnitine, a nutrient abundant in red meat. Gut microbial transformation of L-carnitine into trimethylamine (TMA), the precursor of TMAO, occurs via the intermediate γ-butyrobetaine (γBB). However, the interrelationship of γBB, red meat ingestion and CVD risks, as well as the gut microbial genes responsible for the transformation of γBB to TMA, are unclear. In the present study, we show that plasma γBB levels in individuals from a clinical cohort (n = 2,918) are strongly associated with incident CVD event risks. Culture of human faecal samples and microbial transplantation studies in gnotobiotic mice with defined synthetic communities showed that the introduction of Emergencia timonensis, a human gut microbe that can metabolize γBB into TMA, is sufficient to complete the carnitine → γBB → TMA transformation, elevate TMAO levels and enhance thrombosis potential in recipients after arterial injury. RNA-sequencing analyses of E. timonensis identified a six-gene cluster, herein named the γBB utilization (gbu) gene cluster, which is upregulated in response to γBB. Combinatorial cloning and functional studies identified four genes (gbuA, gbuB, gbuC and gbuE) that are necessary and sufficient to recapitulate the conversion of γBB to TMA when coexpressed in Escherichia coli. Finally, reanalysis of samples (n = 113) from a clinical, randomized diet, intervention study showed that the abundance of faecal gbuA correlates with plasma TMAO and a red meat-rich diet. Our findings reveal a microbial gene cluster that is critical to dietary carnitine → γBB → TMA → TMAO transformation in hosts and contributes to CVD risk.


Inhibitory effect of the CA2+ antagonist nifedipine on histamine release from rat peritoneal mast cells.
45Ca uptake and histamine release was examined in mast cells from rats sensitized with ovalbumin and Bordetella Bertussis as an adjuvant. The uptake of 45Ca by the mast cells was significantly increased by stimulation with ovalbumin as was the release of histamine from the mast cells. Nifedipine, a calcium antagonist, inhibited the increase in both 45Ca uptake and histamine release stimulated by ovalbumin, though the effect on 45Ca uptake was stronger than that on histamine release.


Seasonal distribution of microplastics in the surface water and sediments of the Vellar estuary, Parangipettai, southeast coast of India.
Microplastics (MPs) are toxic pollutants, which are found ubiquitously in the marine environment. The present study aimed to assess the level of MP contamination in Vellar estuary, southeast coast of India. MP abundance in surface water and sediments ranged from 1.15 ± 0.01 to 5.14 ± 0.04 items/m3 and 24.8 ± 0.75 to 43.4 ± 0.98 particles/kg d.w., respectively. Fiber, fragment, film, pellet and glitter were present in the study area. In total, ten colors of MPs were found in the study, of which black was the most abundant. Seven polymers in sediments and four polymers in water were characterized from the study area, among which LDPE was the most dominant. Sediment texture results showed that clay particles were able to retain a greater number of MPs. This study shows that the Vellar estuary is contaminated with MPs; however, further investigation is required to classify the estuary as polluted.


Beta cell destruction in the development of autoimmune diabetes in the non-obese diabetic (NOD) mouse.
In the non-obese diabetic (NOD) mouse model of Type 1 (insulin-dependent) diabetes, evidence suggests that pancreatic beta cells are destroyed in part by apoptotic mechanisms. The precise mechanisms of beta cell destruction leading to diabetes remain unclear. The NOD mouse has been studied to gain insight into the cellular and molecular mediators of beta cell death, which are discussed in this review. Perforin, secreted by CD8(+) T cells, remains one of the only molecules confirmed to be implicated in beta cell death in the NOD mouse. There are many other molecules, including Fas ligand and cytokines such as interferon-gamma, interleukin-1 and tumor necrosis factor-alpha, which may lead to beta cell destruction either directly or indirectly via regulation of toxic molecules such as nitric oxide. As beta cell death can occur in the absence of perforin, these other factors, in addition to other as yet unidentified factors, may be important in the development of diabetes. Effective protection of NOD mice from beta cell destruction may therefore require inhibition of multiple effector mechanisms.


Influence of Immune Myeloid Cells on the Extracellular Matrix During Cancer Metastasis.
The extracellular matrix (ECM) is one of the most important components within the tumor microenvironment that supports cancer development and metastasis. Under normal physiological conditions, the ECM is a tightly regulated network providing structural and biochemical support. However, the ECM becomes highly disorganized during neoplastic progression and consequently, stimulates cancer cell transformation, growth and spread. Cancer development and progression is also known to greatly benefit from the support of immune myeloid cells, which have multiple pro-tumorigenic functions including promoting tumor growth, migration and invasion, stimulating angiogenesis and suppressing anti-tumor responses. An increasing number of studies have shown that myeloid cells alter the ECM to support metastatic cancer progression and in turn, the ECM can influence the function of infiltrating myeloid cells. However, the exact nature of this relationship, such as the mechanisms employed and their molecular targets remains unclear. This review discusses evidence for the reciprocal dependence of myeloid cells and the tumor ECM for efficient tumor development and explores potential mechanisms involved in these interactions. A better understanding of this relationship has exciting implications for the development of new therapeutic treatments for metastatic cancer.


Effect of anti-CD52 antibody alemtuzumab on ex-vivo culture of umbilical cord blood stem cells.
Excessive maturation of hematopoietic cells leads to a reduction of long-term proliferative capability during cord blood (CB) expansion. In this study, we report the effects of anit-CD52 (Alemtuzumab, Campath) on both short- and long-term ex vivo expansion of CB hematopoietic stem cells (HSC) by evaluating the potential role of Alemtuzumab in preserving the repopulating capability in CB HSC and nonlymphoid progenitors. Ex vivo expansion experiments were carried out using freshly purified CB CD34(+)cells in StemSpantrade mark SFEM medium in the presence of stem cell factor, Flt3-Ligand and thrombopoietin at 50 ng/ml. Alemtuzumab (10 microg/ml) was used to deplete CD52(+) cells during the cultures. Flow cytometry was used to monitor CB HSC and their differentiation. Colony forming unit (CFU) assays and long term culture-initiating cell (LTC-IC) assays were performed on cells obtained from day 0 (before culture) and day 14 after cultures. Secondary cultures was performed using CD34(+) cells isolated at 35 days from primary cultures and further cultured in StemSpantrade mark SFEM medium for another 14 days to confirm the long term effect of alemtuzumab in liquid cultures. Compared to cytokines alone, addition of alemtuzumab resulted in a significant increase in total nucleated cells, absolute CD34(+) cells, myeloid and megakaryocytic progenitors, multi-lineage and myeloid CFU and LTC-IC. The results from current study suggested that the use of alemtuzumab for ex vivo expansion of CBHSC maybe advantageous. Our findings may improve current technologies for CBHSC expansion and increase the availability of CB units for transplantation. However, in vivo studies using animal models are likely needed in further studies to test the hematopoietic effects using such expanded CB products.


Broadband surface plasmon resonance sensor for fast spectroscopic photoacoustic microscopy.
High-speed optical-resolution photoacoustic microscopy (OR-PAM), integrating the merits of high spatial resolution and fast imaging acquisition, can observe dynamic processes of the optical absorption-based molecular specificities. However, it remains challenging for the evaluation to morphological and physiological parameters that are closely associated with photoacoustic spectrum due to the inadequate ultrasonic frequency response of the routinely-employed piezoelectric transducer. By utilizing the galvanometer for fast optical scanning and our previously-developed surface plasmon resonance sensor as an unfocused broadband ultrasonic detector, high-speed spectroscopic photoacoustic imaging was accessed in the OR-PAM system, achieving an acoustic bandwidth of ∼125 MHz and B-scan rate at ∼200 Hz over a scanning range of ∼0.5 mm. Our system demonstrated the dynamic imaging of the moving phantoms' structures and the simultaneous characterization of their photoacoustic spectra over time. Further, fast volumetric imaging and spectroscopic analysis of microanatomic features of a zebrafish eye ex vivo was obtained label-freely.


Three-dimensional and power Doppler ultrasonography in infertility and reproductive endocrinology.
Three-dimensional (3D) ultrasound is an easy and noninvasive technique in the clinical practice of obstetrics and gynecology. It can be used in the analysis of morphologic anatomy and volume measurement and is highly reproducible. Power Doppler ultrasound can further depict and quantify the microcirculation of the target organ or the region of interest. The aim of this review is to report the present status and the development of 3D ultrasonography, as well as 3D power Doppler in the field of infertility and reproductive endocrinology. 3D ultrasound may help us investigate the functional and potential roles in various pathologic conditions of the female pelvis. Furthermore, 3D ultrasound may also provide substantial assistance in the clinical application of infertility and reproductive endocrinology.


Synergistic interaction between acivicin (AT-125) and 6-thioguanine in the murine leukemia L1210. Biochemical and cytokinetic considerations.
The effect of the purine antagonist acivicin (AT-125) on the metabolism and cytotoxicity of 6-thioguanine was examined in the murine leukemia L1210. Cells exposed to 5 X 10(-6) M acivicin for 18 hr followed by 10(-5) M [14C]-6-thioguanine for 2 hr accumulated 2.90 +/- 0.17 nmoles 6-thioguanine/10(6) cells compared to 0.69 +/- 0.07 nmoles 6-thioguanine/10(6) cells in untreated controls. Intracellular accumulation of 6-thioguanine monophosphate, a lethal 6-thioguanine metabolite, increased from 0.27 +/- 0.05 to 1.08 +/- 0.13 nmoles 6-thioguanine monophosphate/10(6) cells following the same acivicin exposure. A similar increment was observed for the formation of 6-thioguanine triphosphate. These alterations in 6-thioguanine metabolism were associated with an increase in the intracellular level of 5-phosphoribosyl-1-pyrophosphate, an obligatory substrate in 6-thioguanine activation (57.9 +/- 7.6 vs 13.4 +/- 2.3 ng 5-phosphoribosyl-1-pyrophosphate/10(6) cells). In contrast, there was a 50% reduction in the amount of 6-thioguanine incorporated into RNA and DNA following acivicin pretreatment. Cytofluorometric analysis revealed that an 18-hr exposure to 5 X 10(6) M acivicin increased the population 5-phase cells, which are more sensitive to the actions of 6-thioguanine, by 50% relative to untreated controls. In both suspension culture growth and soft agar studies, the sequential administration of acivicin followed by 6-thioguanine resulted in substantial growth inhibitory activity; in contrast, the effects of the reverse sequence were subadditive. Pretreatment of L1210 cells with acivicin potentiates the action of subsequently administered 6-thioguanine, and the mechanism may involve both biochemical as well as cytokinetic factors. In vivo studies involving the sequential administration of these agents appear warranted.


Gene expression profiling of HIV-1 infection using cDNA microarrays.
To illustrate the methods employed in gene expression profiling using cDNA microarrays, infection of CD4+ T cell lines with HIV-1LAI is used to identify expression changes relevant to in vitro HIV-1 infection. Cell lines are infected at a high multiplicity of infection to ensure a population of near-synchronously infected cells to be compared to uninfected cells. Infection status is verified using flow cytometry to determine the intracellular expression of the viral gag p24 protein before samples are harvested for total RNA extraction. Total RNA is extracted and amplified using commercially available kits, and RNA quality is verified using Bioanalyzer technology. To obtain fluorescently labeled cDNA probes, the amplified RNA is reverse-transcribed to yield cDNA, using random nonamers in the presence of dye-labeled dCTP. After first-strand cDNA synthesis, RNA is degraded and the probes are purified. For each infection condition (LAI and mock), two slides are hybridized with identical probes generated from the same RNAs, but with fluorescent labels reversed on one of the slides to control for dye-specific effects. Troubleshooting strategies and issues to consider prior to starting the experiment are discussed in detail in the notes section.


A protocol on the effects of interactive digital assistance on engagement and perceived quality of care of surgery patients and self-efficacy and workload of staff.
The workforce shortage in the healthcare context is a growing issue that exerts detrimental effects on employees (e.g., higher workload) and patients (e.g., suboptimal patient care). Since traditional approaches alone may not be enough to solve this problem, there is a need for complementary innovative digital health solutions, such as socially assistive robots. Hence, the proposed study aims to investigate the effects of gamified nursing education and physiotherapy delivered by a socially assistive robot on patient- (engagement, perceived quality of care) and employee-related outcomes (perceived self-efficacy, workload). Approximately 90 vascular and thoracic surgery patients will receive either standard care or standard care with additional robot interactions over the course of 3-5 days. Additionally, approximately 34 nursing and physiotherapeutic employees will fill out self-report questionnaires after weeks of not using a social robot and weeks of using a social robot. The main hypotheses will be tested with mixed-design analyses of variance and paired-samples t-tests. While the proposed study has some limitations, the results will provide high-quality and comprehensive evidence on the effectiveness of socially assistive robots in healthcare. The study was approved by the Medical Ethics Commission of the University Medical Center and registered in the ISRCTN registry (ISRCTN96689284). The study findings will be summarized in international peer-reviewed scientific journals and meetings and communicated to relevant stakeholders.


Unhooking of GSB total knee during dislocation of the patella.
This is a case report of a special and undoubtedly rare complication occurring in a hinge joint with a moving instant center such as the GSB total knee joint. The preoperative situation, the history of the incident and the operative report are being described as well as a radiological follow-up. The mechanism of unhooking of the tibial shaft from its junction with the femoral stem during dislocation of the patella is being reconstructed.


Bacterial infections of the skin treated with ciprofloxacin.
Bacterial infections of the skin or soft tissue responded to ciprofloxacin 500 mg tablets b.i.d. The treatment was well tolerated and effective, so that this drug can be recommended in cutaneous infections caused by sensitive bacteria.


Ethics and the clinician in custody disputes.
This article stresses the need to separate the role of therapist from that of forensic evaluator in custody disputes. Common pitfalls for the therapist who testifies in custody disputes are discussed, and ethical guidelines for both the therapist and the forensic evaluator are provided.


Hyperuricemia and acute gout after laparoscopic sleeve gastrectomy.
The aim of this study was to evaluate the prevalence of hyperuricemia and acute gout after laparoscopic sleeve gastrectomy (LSG). Risk factors for developing gout were also examined. Eighty-five patients underwent LSG were enrolled in this prospective study. Serum uric acid levels, gout attacks and total water levels % derived by bioimpedance were examined pre-operatively and 1 month post-operatively. Hyperuricemia was identified in 30.6% pre-operatively and in 18.82% of patients post-operatively. From the patients' group with pre-operative hyperuricemia, 53.9% were normalized, 46.2% had increased uric acid post-operatively while gout was observed in 11.5%. From the patients group without pre-operative hyperuricemia, hyperuricemia and gout were observed in 6.8% and 5.1% post-operatively, respectively. The relative risk for developing hyperuricemia was 6.2 (95% confidence interval [CI] 2.2-17.8) and for developing gout was 2.3 (95% CI 2.2-17.8). Statistical significant differences for gout among the groups with and without gout were indicated concerning pre-operative use of medications (P < 0.001), age (P = 0.025), post-operative uric acid levels (P < 0.001) and post-operative total water levels % (P = 0.048). The prevalence of hyperuricemia was 18.8% and gout attack of 7.1% 1 month after LSG. From the cohort of patients with pre-operative hyperuricemia, a significant proportion normalized uric acid, while 11.5% developed gout. Patients without hyperuricemia pre-operatively developed hyperuricemia and gout in 6.8% and 5.1% post-operatively, respectively. The patients who had gout were younger and had 37% water levels post-operatively.


Prognostic value of pretreatment FDG PET in pediatric neuroblastoma.
This study aimed to evaluate the prognostic value of pretreatment (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in pediatric neuroblastoma patients. The study included 50 pediatric neuroblastoma patients who underwent diagnostic work-up FDG PET before any treatment. The maximum standardized uptake value (SUV(max)) of the primary tumor lesion (P(max)), the SUV(max) of all the tumor lesions, including the primary tumor lesion and metastatic lesions (T(max)), and the uptake ratio of T(max) to mean SUV of normal liver tissue (T(max)/L(mean)) were calculated and tested as prognostic factors. Of the 50 patients, 15 (30.0%) experienced disease progression and 21 (42.0%) died during the follow-up period. On univariate analysis, the histopathology, tumor stage, bone marrow involvement, serum levels of lactate dehydrogenase (LDH), neuron-specific enolase, and ferritin, primary tumor size, P(max), T(max), and T(max)/L(mean) were significant prognostic factors for disease progression-free survival (PFS), whereas the tumor stage, serum level of LDH, T(max), and T(max)/L(mean) were determined to be significant for predicting overall survival (OS). On multivariate analysis, the histopathology and serum level of LDH were independent prognostic factors for PFS, and only the T(max)/L(mean) was an independent prognostic factor for OS. The 2-year PFS and OS rates were over 80.0% in patients with low FDG uptake, meanwhile, patients with high FDG uptake showed the 2-year PFS of less than 30.0% and OS of less than 55.0%. FDG PET was an independent prognostic factor for OS in neuroblastoma patients. FDG PET can provide effective information on the prognosis for neuroblastoma patients.


[Contribution of the new oral anticoagulants to the treatment of acute coronary syndrome].
Acute coronary syndrome (ACS) occurs as a result of atherosclerotic plaque rupture and subsequent platelet activation and coagulation leading to thrombus formation and coronary occlusion. Thrombin and activated factor X (FXa) are key elements in the coagulation cascade. The use of anticoagulants in ACS, both in the acute phase and in the long term, has improved prognosis by reducing thrombotic events, but is associated with an increased risk of bleeding. In recent years, new oral anticoagulants have been developed that do not require monitoring and produce a lower risk of bleeding. Rivaroxaban is the only drug with a favorable risk-benefit profile in patients with ACS. The ATLAS ACS TIMI 2-51 is the first phase III trial demonstrating that the addition of low-dose rivaroxaban to optimal antiplatelet therapy reduces mortality, cardiovascular mortality, infarct or stroke without significantly increasing fatal bleeding.


Alterations in serum cortisol, CD4+ CD8+ lymphocyte sub-population ration and T cell mediated suppression of immune responses in the malnutrition of anorexia nervosa.
Serum cortisol and T lymphocyte sub-populations (CD3+, 4+ and 8+) were studied in 22 consecutively admitted patients with anorexia nervosa (AN) who had a mean weight loss of 30%. In addition Concanavalin A (Con A) mitogen induced T cell suppression of lymphocyte response to PPD (purified protein derivative of tuberculin antigen) was analysed. Increased serum cortisol concentrations were found in the AN-patients compared to the control group, with mean levels 654 and 418 nmol/l respectively. The relative numbers of CD4+ lymphocytes (mean 36.2%) and the CD4+ CD8+ ratio (mean 1.54) were significantly reduced (p < 0.05) in the AN-patients compared to the control group (mean 41.6% and 2.14 respectively). T cell mediated, Con A induced suppression of lymphocyte response to PPD was increased in AN-patients compared to the control group with low (1mug/ml) Con A concentration, but unchanged with high (5 mug/ml) Con A concentration. There was no correlation between serum cortisol concentrations and the numbers of T lymphocyte subpopulations or T cell suppressor activity. In contrast, a highly significant correlation existed between serum cortisol and the duration of AN (p < 0.002), but not with relative weight loss or anthropometric variables: triceps skin-fold (TSF) and arm muscle circumference (AMC). Immunological variables were not correlated with duration of disease. Thus, immunological alterations of the T cell system are detectable in AN, but are subtle and their clinical importance is not well known.


Follicular aspiration during the selection phase prevents severe ovarian hyperstimulation in patients with polycystic ovary syndrome who are undergoing in vitro fertilization.
The objective was to assess the effectiveness of follicular aspiration in the selection phase of infertile women with polycystic ovary syndrome (PCOS) under controlled ovarian hyperstimulation (COH). In group A, 13 infertile patients with PCOS failed at previous IVF or intracytoplasmic sperm injection (ICSI) treatment due to ovarian hyperstimulation syndrome (OHSS; a total of 13 cycles). In group B, new IVF cycles with ultrasound-guided transvaginal follicular aspirations during the selection phase (a total of 13 cycles) were conducted using the same patients. No more than ten follicles remained in bilateral ovaries. Parameters monitored included ovarian size, number of dominant follicles, estradiol (E2) level on the day of human chorionic gonadotrophin (HCG) injection, maturation of oocytes, fertilization rate, cleavage rate, embryo implantation rate, pregnancy rate, and level of serum hormone. In group B, the average number of follicles>or=12 mm and average serum E2 level were 15.5+/-4.0 and 9899+/-1430 pmol/l, respectively, which were significantly lower than 29.1+/-8.4 (P<0.001) and 15,544+/-1766 pmol/l (P<0.001) in group A. No cycles with moderate or severe OHSS occurred in group B, while nine out of 13 (69.2%) cycles did have this problem in group A. Oocyte maturation rate, fertilization rate and cleavage rate in group B were 80.7%, 76.9%, and 80.3%, respectively; and all of them are significantly higher than 56.4% (P<0.01), 58.7% (P<0.01), and 70.2% (P<0.02) respectively in group A. Follicular aspiration during the selection phase can prevent severe OHSS and reduce OHSS prevalence in patients with PCOS undergoing COH.


Is there a human fear paradox? A more thorough use of comparative data to test the fearful ape hypothesis.
Grossmann's intriguing proposal can benefit from a more thorough integration of the primate literature, particularly on neophobia. Moreover, it directly leads to strong predictions in callitrichids, the only other cooperatively breeding primates beyond humans, which may indeed be met: Being more likely to signal distress than independently breeding monkeys, and responding to such signals with approach and affiliation.


Impact of navigated-control assistance on performance, workload and situation awareness of experienced surgeons performing a simulated mastoidectomy.
Navigated control (NC) is an advanced image-guided navigation system that provides an additional control function to enhance patient safety. It automatically stops the surgical instrument if it comes close to critical anatomical structures that need to be protected during surgery. The purpose of this study was to explore the human performance consequences of computer-based navigated control assistance. Seven experienced surgeons conducted a simulated mastoidectomy manually and with support of the NC system. The impact on surgical performance, workload and situation awareness was analysed. NC support led to a better quality of surgical outcome and a lower level of physiological effort during surgery. Cost effects were reflected in reduced time efficiency and an increased subjectively experienced workload. The results demonstrate the potential of NC support in terms of lower workload and enhanced patient safety. Cost effects might be reduced by remodelling the control function.


Mechanical properties, in vitro corrosion resistance and biocompatibility of metal injection molded Ti-12Mo alloy for dental applications.
A biocompatible Ti-12Mo alloy was fabricated by metal injection moulding (MIM) using non-spherical titanium, molybdenum powders and a purposely designed binder. The density, microstructure and tensile properties were characterized. This was followed by a detailed assessment of its in vitro corrosion and biocompatibility performances, compared with that of two commonly used titanium-based materials extra low interstitial (ELI) Ti-6Al-4V and commercially pure (CP) titanium. The MIM-fabricated Ti-12Mo alloy can achieve a wide range of mechanical properties through controlling sintering process. Specimens sintered at 1400 °C are characterized by fairly uniform near-β microstructure and high relative density of 97.6%, leading to the highest tensile strength of 845.3 ± 21 MPa and elongation of 4.15 ± 0.2% while the highest elastic modulus of 73.2 ± 5.1 GPa. Owing to the formation of protective TiO2-MoO3 passive film, the MIM-fabricated Ti-12Mo alloy exhibits the highest corrosion resistance including the noblest corrosion potential, the lowest corrosion current density and the highest pitting potential in four different electrolytes. The in vitro cytotoxicity test suggests that the MIM-fabricated Ti-12Mo alloy displays no adverse effect on MC3T3-E1 cells with cytotoxicity ranking of 0 grade, which is nearly close to ELI Ti-6Al-4V or CP Ti. These properties together with its easy net-shape manufacturability make Ti-12Mo an attractive new dental implant alloy.


Analysis of inhibitory effects of scutellariae radix and baicalein on prostaglandin E2 production in rat C6 glioma cells.
Inhibitory mechanism of the water extract of Scutellariae Radix on prostaglandin E2 (PGE2) release was examined in C6 rat glioma cells. Scutellariae Radix reduced a Ca2+ ionophore A23187-induced PGE2 release by inhibition of arachidonic acid (AA) liberation. Sho-saiko-to and San'o-shashin-to, which contain Scutellariae Radix, also inhibited PGE2 release. A23187 caused phosphorylation of mitrogen-activated protein kinase (MAPK), resulting in activation of cytosolic phospholipase A2 (cPLA2). Scutellariae Radix and baicalein inhibited the phosphorylation of MAPK. Baicalein, but not baicalin, inhibited A23187-induced PGE2 release. These results suggest that baicalein in Scutellariae Radix reduces AA liberation through the inhibition of the MAPK-cPLA2 pathway.


MPP+-induced increases in extracellular potassium ion activity in rat striatal slices suggest that consequences of MPP+ neurotoxicity are spread beyond dopaminergic terminals.
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) produces symptoms similar to idiopathic Parkinson's disease in primates. A metabolite of MPTP, MPP+ (1-methyl-4-phenylpyridinium), is actively accumulated by dopaminergic (DA) terminals and selectively destroys nigrostriatal DA neurons. The mechanism of this effect remains unknown but reports that MPP+ inhibits electron transport in isolated mitochondria and increases oxidation of cytochrome b in striatal slices suggest that depression of ATP production is involved. To relate metabolic effects of MPP+ with tissue electrophysiology, extracellular potassium ion activity [K+]o was measured by microelectrodes simultaneous to optical monitoring of reduction/oxidation (redox) activity of cytochrome b during superfusion of MPP+ onto rat striatal and hippocampal slices. MPP+ increased oxidation of cytochrome b and increased [K+]o in slices of striatum. These increases were greater than expected from a selective effect of MPP+ on DA terminals which likely comprise no more than 3% of the total striatal mass. These effects of MPP+ were slowed by a dopamine uptake inhibitor (mazindol) and did not occur in hippocampal slices. These findings indicate that MPP+ influences ion transport as well as metabolic activity and that these actions require the presence of functioning DA terminals. However, the large amplitudes of the MPP+-induced changes suggest that consequences of MPP+-neurotoxicity are not ultimately confined to DA terminals. Two hypothesis are proposed: that energy failure in DA terminals results in leakage of neurotoxic substances or metabolites altering membrane conductance properties of adjacent cells and thereby placing additional demand upon ion transport pumps and mitochondrial oxidative phosphorylation; or that there is secondary uptake of MPP+ leading to mitochondrial inhibition in cells neighboring DA terminals.


Rat urinary metabolites of [9,10-methylene-14C] sterculic acid.
1. The metabolism of [9,10-methylene-14C] sterculic acid was studied in corn oil and Stercula foetida oil fed rats. The majority of the radioactivity was excreted into the urine as short chain dicarboxylic acids. The main urinary metabolites were cis-3,4-methylene adipic acid, cis-3,4-methylene suberic acid, trans-3,4-methylene adipic acid, cis-3,4-methylene pimelic acid, and cis-3,4-methylene azelic acid. 2. Formation of these urinary metabolites requires alpha-, beta-, and omega-oxidation plus reduction of the cyclopropene ring to a cyclopropane ring. Sterculic acid must be transported through both mitochondrial and microsomal systems. 3. Other non-radioactive urinary compounds were also identified. A proposed pathway for the metabolism of sterculic acid and possible detrimental effects caused by these metabolites is discussed.


Effect of human growth hormone therapy on head circumference in children with hypopituitarism.
Head circumference was measured before and during hGH therapy in fourteen children with isolated growth hormone deficiency (IGHD) and in twenty-one children with multiple pituitary hormone deficiencies (MPHD). In both groups there was a retardation in growth of the neurocranium, more marked in the children with IGHD, which was less than the retardation in linear height. In the group with IGHD, initiation of hGH therapy before a chronological age of 5 and a bone age of 3 had been reached led to a rapid catch-up in cranial growth with normalization of the head size. In older children the induction of head growth was similar to that achieved by the long bones but without a true catch-up phenomenon. In three adults with hereditary IGHD without therapy or with irregular treatment during late puberty, the head circumference was below normal range. In view of the possible role played by development of brain tissue upon cranial size, the importance of early diagnosis and initiation of therapy in infants and young children with a deficiency of hGH is stressed.


Systemic therapy of disseminated malignant melanoma: an evidence-based overview of the state-of-the-art in daily routine.
In the metastatic stage, malignant melanoma is resistant to systemic treatment and carries a poor prognosis. A critical, evidence-based analysis of standard approaches based on an extended search of published literature and from different Internet sources is presented. A critical, evidence-based analysis of standard approaches and their variations to systemic therapy based on an extended search of published literature and from different Internet sources is presented. Few meta-analyses are available. Therefore, assessment of therapies is mainly based on randomized multicentre studies or clinical studies achieving an evidence level grade 1 or 2. Monotherapy with DTIC (dacarbazine) is the standard. Based on overall survival data, polychemotherapies cannot be recommended. Combination of polychemotherapy with the cytokines interferon-alpha and interleukin-2 substantially augments chemotherapy induced response rates, but a meta-analysis for survival does not support its therapeutic superiority. Biological therapies such as vaccinations have not yet delivered results on a higher evidence level. Thus, immunotherapies as well as chemo-immunotherapies will have to be evaluated in further studies. Although the therapeutic efficacy is very limited, dacarbazine cannot be rejected as standard therapy for disseminated melanoma, because no other therapeutic regimen exhibits a survival benefit over DTIC in an evidence-based analysis. This lack of therapeutic progress over the past 40 years clearly calls for further clinical studies, and patients should be enrolled into clinical trials whenever possible.


Cross-Sectional Location of Gastric Cancer Affects the Long-Term Survival of Patients as Tumor Invasion Deepens.
The prognosis of gastric cancer is generally determined by tumor depth and lymph node metastasis, while the effect of cross-sectional tumor location on prognosis remains unclear. This study recruited patients who had been diagnosed with gastric cancer and who underwent gastrectomy from 1989 to 2012. The cross-sectional locations of the gastric cancers were classified into four regions: the lesser (LC) and greater curvatures (GC), and anterior (AW) and posterior walls (PW). Overall, 4820 patients were enrolled in this study. The most common site of gastric cancer among the four cross-sectional locations was the LC (46.4%), while the proportions of PW (19.9%), AW (18.4%), and GC (15.4%) were similar. Overall survival differed statistically (p = 0.013) according to the cross-sectional location, and the 5-year overall survival of those with tumors with a GC location was significantly worse (p = 0.003) than for the other three locations. In subgroup multivariate analysis, GC location was an independent prognostic indicator for a worse clinical outcome at T stage 3-4b (hazard ratio 1.365, 95% confidence interval 1.150-1.620, p < 0.001). In addition, a GC gastric cancer had a higher recurrence rate in terms of peritoneal seeding compared with other locations. The cross-sectional location of gastric cancer is associated with long-term survival. A GC location predicts a worse prognosis, especially in gastric cancer patients with deeper T stages.


Comparison of breast density assessment between human eye and automated software on digital and synthetic mammography: Impact on breast cancer risk.
To evaluate the agreement between automatic assessment software of breast density based on artificial intelligence (AI) and visual assessment by a senior and a junior radiologist, as well as the impact on the assessment of breast cancer risk (BCR) at 5 years. We retrospectively included 311 consecutive women (mean age, 55.6±8.5 [SD]; range: 40-74 years) without a personal history of breast cancer who underwent routine mammography between January 1, 2019 and February 28, 2019. Mammographic breast density (MBD) was independently evaluated by a junior and a senior reader on digital mammography (DM) and synthetic mammography (SM) using BI-RADS (5th edition) and by an AI software. For each MBD, BCR at 5 years was estimated per woman by the AI software. Interobserver agreement for MBD between the two readers and the AI software were evaluated by quadratic κ coefficients. Reproducibility of BCR was assessed by intraclass correlation coefficient (ICC). Agreement for MBD assessment on DM and SM was almost perfect between senior and junior radiologists (κ=0.88 [95% CI: 0.84-0.92] and κ=0.86 [95% CI: 0.82-0.90], respectively) and substantial between the senior radiologist and AI (κ=0.79; 95% CI: 0.73-0.84). There was substantial agreement between DM and SM for the senior radiologist (κ=0.79; 95% CI: 0.74-0.84). BCR evaluation at 5 years was highly reproducible between the two radiologists on DM and SM (ICC=0.98 [95% CI: 0.97-0.98] for both), between BCR evaluation based on DM and SM evaluated by the senior (ICC=0.96; 95% CI: 0.95-0.97) or junior radiologist (ICC=0.97; 95% CI: 0.96-0.98) and between the senior radiologist and AI (ICC=0.96; 95% CI: 0.95-0.97). This preliminary study demonstrates a very good agreement for BCR evaluation based on the evaluation of MBD by a senior radiologist, junior radiologist and AI software.


Antiproliferative and Apoptotic Effects of pH-Responsive Veratric Acid-Loaded Polydopamine Nanoparticles in Human Triple Negative Breast Cancer Cells.
Veratric acid (VA) is plant-derived phenolic acid known for its therapeutic potential, but its anticancer effect on highly invasive triple-negative breast cancer (TNBC) is yet to be evaluated. Polydopamine nanoparticles (nPDAs) were chosen as the drug carrier to overcome VA's hydrophobic nature and ensure a sustained release of VA. We prepared pH-sensitive nano-formulations of VA-loaded nPDAs and subjected them to physicochemical characterization and in vitro drug release studies, followed by cell viability and apoptotic assays on TNBC cells (MDA-MB-231 cells). The SEM and zeta analysis revealed spherical nPDAs were uniform size distribution and good colloidal stability. In vitro drug release from VA-nPDAs was sustained, prolonged and pH-sensitive, which could benefit tumor cell targeting. MTT and cell viability assays showed that VA-nPDAs (IC50=17.6 μM) are more antiproliferative towards MDA-MB-231 cells than free VA (IC50=437.89 μM). The induction of early and late apoptosis by VA-nPDAs in the cancer cells was identified using annexin V and dead cell assay. Thus, the pH response and sustained release of VA from nPDAs showed the potential to enter the cell, inhibit cell proliferation, and induce apoptosis in human breast cancer cells, indicating the anticancer potential of VA.


The reversible oxidation of vicinal SH groups in 4-aminobutyrate aminotransferase. Probes of conformational changes.
4-Aminobutyrate aminotransferase is inactivated by preincubation with iodosobenzoate at pH 7. The reaction of 2 SH residues/dimer resulted in formation of an oligomeric species of Mr = 100,000 detectable by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The subunits cross-linked via a disulfide bond are dissociated by addition of 2-mercaptoethanol which also restores full catalytic activity (Choi, S. Y., and Churchich, J.E. (1985) J. Biol. Chem. 260, 993-997). The substrate 2-oxoglutarate prevents inactivation of the enzyme by iodosobenzoate and the subsequent formation of one disulfide bond, whereas 4-aminobutyrate has no effect on the reactivity of SH groups with iodosobenzoate. Modified 4-aminobutyrate aminotransferase (containing 1 disulfide bond) catalyzes a half-transamination reaction; but it is unable to react with 2-oxoglutarate to generate the aldimine form of the enzyme. The spectroscopic properties (fluorescence yield and polarization of fluorescence) of PMP bound to the modified enzyme are different from those of pyridoxamine phosphate (PMP) bound to the native enzyme. The polarization of fluorescence values of PMP bound to the cross-linked enzyme, excited over the spectral range 310-370 nm, are greater (25%) than those of the cofactor of the native enzyme. An increase in the polarization values implies that the motion of PMP is restricted when the subunits are cross-linked via a disulfide bond.


Health and ecological risk-based characterization of soil and sediment contamination in shipyard with long-term use of DDT-containing antifouling paint.
Dichlorodiphenyltrichloroethane (DDT) was a frequently occurring type of persistent organic environmental pollutant in China and DDT-containing antifouling paint could be the main contributor of DDT to shipyards and fishing harbors. A field survey was conducted in a shipyard in southern China to investigate the content and distribution of DDT in soil and sediments. Human health and screening-level ecological risk assessments were conducted for DDT contamination in soil and sediments and the results indicated that total DDT in all samples tested exceeded present advisory safe limits. Analysis of the composition and distribution implicated DDT-containing antifouling paint used for ship maintenance as an important source of DDT. Individual and cumulative health risks for residents exceeded the extra lifetime cancer risks of 10(-6) and 10(-5), mainly from exposure to soil, ingestion and dermal contact. DDT in sediments is associated with a high level of toxicity for the benthic community when >99% of samples exceed the threshold concentration likely to be responsible for effects and severe effects. Further risk control for DDT is required to ensure safety for human health, the benthic community and the environment.


[Costeff syndrome: a syndrome that was described in Israel and the responsible gene discovered by an Israeli doctor].
Costeff syndrome or 3-methylglutaconic aciduria type 3, was described by a group of Israeli doctors in 1989. Since then more than 40 patients were described. Most of the patients are of Iraqi-Jewish origin. The clinical abnormalities are bilateral optic atrophy, extrapyramidal signs, spasticity ataxia, dysarthria and mild cognitive deficit. Recently, the gene responsible for this disorder, OPA3 gene was identified. This gene was also discovered by an Israeli doctor. This is a case history of a patient with Costeff syndrome presenting the characteristics of this syndrome and the gene that causes this disease.


Chromosomal integrity of human preimplantation embryos at different days post fertilization.
In order to investigate the dynamics of genomic alterations that occur at different developmental stages in vitro, we examined the chromosome content of human preimplantation embryos by molecular-cytogenetic techniques at the single-cell level, up to 13 days post fertilization. The embryos were genetically analyzed several times during their development in culture; each embryo was first analyzed by FISH at 'Day 3' post fertilization, than during its growth in vitro and the third analysis was performed at development arrest, then the entire blastocyst was analyzed by comparative genomic hybridization (CGH/aCGH). We found that while on 'Day 3' only 31% of the embryos were detected as normal, on 'Day 5-6', 44% of the embryos were classified as normal and on 'Day 7', 57% were normal. On 'Days 8-13', 52% of the embryos were classified as chromosomally normal. One third of the embryos that were chromosomally abnormal on 'Day 3', were found to be normal at development arrest point. These dynamic changes that occur at early developmental stages suggest that testing a single blastomere at 'Day 3' post fertilization for PGD might inaccurately reflect the embryo ploidy and increase the risk of false aneuploidy diagnosis. Alternatively, blastocyst stage diagnosis may be more appropriate.


Comparison of lncRNA Expression in the Uterus between Periods of Embryo Implantation and Labor in Mice.
Uterine function during pregnancy is regulated mainly by progesterone (P4) and estrogen (E2). Serum P4 levels are known to fluctuate significantly over the course of pregnancy, especially during embryo implantation and labor. In this study, pregnant mice at E0.5, E4.5, E15.5, and E18.5 (n = 3/E) were used for an RNA-Seq-based analysis of mRNA and lncRNA expression. In this analysis, 1971 differentially expressed (DE) mRNAs, 493 known DE lncRNAs, and 1041 novel DE lncRNAs were found between E0.5 and E4.5 at the embryo implantation stage, while 1149 DE mRNAs, 192 known DE lncRNAs, and 218 novel DE lncRNAs were found between E15.5 and E18.5 at the labor stage. The expression level of lncRNA-MMP11 was significantly downregulated by P4 treatment on MSM cells, while lncRNA-ANKRD37 was significantly upregulated. Notably, 117 DE mRNAs, 19 known DE lncRNAs, and 31 novel DE lncRNAs were commonly expressed between the two stages, indicating that these mRNAs and lncRNAs may be directly or indirectly regulated by P4.


Indications, techniques, outcomes, and limitations for minimally ischemic and off-clamp partial nephrectomy: a systematic review of the literature.
On-clamp partial nephrectomy (PN) has been considered the standard approach to minimize intraoperative bleeding and thus achieve adequate control of tumor margins. The potential negative impact of ischemia on renal function (RF) led to the development of techniques to minimize or avoid renal ischemia, such as off-clamp PN and minimally ischemic PN techniques. To review current evidence on the indications and techniques for and outcomes of minimally ischemic and off-clamp PN. A systematic review of English-language publications on PN without a main renal artery clamp from January 2005 to July 2014 was performed using the Medline, Embase, and Web of Science databases. The searches retrieved 52 papers. Off-clamp PN has been more commonly applied to small and peripheral renal tumors, while minimally ischemic PN is best suited for hilar and medially located renal tumors. These approaches are associated with increased intraoperative blood loss and perioperative transfusion rates compared to on-clamp PN. Minimally ischemic and off-clamp PN have potential functional benefits when longer ischemia time is anticipated, particularly for patients with lower baseline RF. Limitations include the lack of prospective randomized trials comparing minimally ischemic and off-clamp to on-clamp techniques, and the small sample size and short follow-up of most published series. The impact of different resection and renorrhaphy techniques on postoperative RF and its assessment via renal scintigraphy requires further investigations. Minimally ischemic and off-clamp PN are established procedures that may be particularly applicable for patients with decreased baseline RF. However, these techniques are technically demanding, with potential for increased blood loss, and require considerable experience with PN surgery. The role of ischemia in patients with a contralateral healthy kidney and consequently an indication for elective minimally ischemic or off-clamp PN remains a debatable issue. In this review we analyzed available evidence on minimally ischemic and off-clamp partial nephrectomy. These techniques, although technically demanding, may be particularly applicable for patients with decreased baseline renal function.


Effect of biochar addition on short-term N2O and CO2 emissions during repeated drying and wetting of an anthropogenic alluvial soil.
Agricultural soils are an important source of greenhouse gases (GHG). Biochar application to such soils has the potential of mitigating global anthropogenic GHG emissions. Under irrigation, the topsoils in arid regions experience repeated drying and wetting during the crop growing season. Biochar incorporation into these soils would change the soil microbial environment and hence affect GHG emissions. Little information, however, is available regarding the effect of biochar addition on carbon dioxide (CO2) and nitrous oxide (N2O) emissions from agricultural soils undergoing repeated drying and wetting. Here, we report the results of a 49-day aerobic incubation experiment, incorporating biochar into an anthropogenic alluvial soil in an arid region of Xinjiang Province, China, and measuring CO2 and N2O emissions. Under both drying-wetting and constantly moist conditions, biochar amendment significantly increased cumulative CO2 emission. At the same time, there was a significant reduction (up to ~20 %) in cumulative N2O emission, indicating that the addition of biochar to irrigated agricultural soils may effectively slow down global warming in arid regions of China.


A simple and sensitive nonradioactive method for the detection of urinary human chorionic gonadotropin and diagnosis of early human pregnancy. I. Multiple-unit test.
A simple, sensitive, and reproducible method for the detection of urinary human chorionic gonadotropin (hCG) and diagnosis of early human pregnancy is reported. A 5-ml aliquot of filtered early-morning urine sample was concentrated in a microconcentrator (M) to 0.1 ml of retentate which was diluted with 0.4 ml of distilled water and tested in a hemagglutination inhibition test (M-HIT). Also, a 0.1-ml aliquot of filtered unconcentrated urine sample was diluted with 0.4 ml of distilled water and tested in the same hemagglutination inhibition test (HIT). Urine samples from women of reproductive age; from perimenopausal, menopausal, and proteinuric women; and from adult males were tested in the HIT and M-HIT. Some of these urine samples were also tested in the mouse ovulation bioassay (MOB). The M-HIT was significantly more reliable than the HIT for diagnosis of early pregnancy 25 to 55 days after menses. Correct negative results with the M-HIT were obtained in urine samples of most of the nonpregnant cycling, perimenopausal, and menopausal women, and adult males. Urine samples from subjects with severe proteinuria gave false-positive types of reactions in the M-HIT. Positive results were obtained in the MOB with a number of urine samples from pregnant, perimenopausal, and menopausal women. A properly conducted M-HIT should be very valuable in diagnosing pregnancy as early as the 26th day of the cycle in regularly menstruating women.


Aortic root and hemiarch replacement in osteogenesis imperfecta.
We describe a case of osteogenesis imperfecta in a 52-year-old man who underwent successful repair of aortic root dilatation and aortic valve insufficiency, using a bioprosthetic aortic valve anastomosed to an interposition graft.


iTRAQ proteomics analysis reveals that PI3K is highly associated with bupivacaine-induced neurotoxicity pathways.
Bupivacaine, a commonly used local anesthetic, has potential neurotoxicity through diverse signaling pathways. However, the key mechanism of bupivacaine-induced neurotoxicity remains unclear. Cultured human SH-SY5Y neuroblastoma cells were treated (bupivacaine) or untreated (control) with bupivacaine for 24 h. Compared to the control group, bupivacaine significantly increased cyto-inhibition, cellular reactive oxygen species, DNA damage, mitochondrial injury, apoptosis (increased TUNEL-positive cells, cleaved caspase 3, and Bcl-2/Bax), and activated autophagy (enhanced LC3II/LC3I ratio). To explore changes in protein expression and intercommunication among the pathways involved in bupivacaine-induced neurotoxicity, an 8-plex iTRAQ proteomic technique and bioinformatics analysis were performed. Compared to the control group, 241 differentially expressed proteins were identified, of which, 145 were up-regulated and 96 were down-regulated. Bioinformatics analysis of the cross-talk between the significant proteins with altered expression in bupivacaine-induced neurotoxicity indicated that phosphatidyl-3-kinase (PI3K) was the most frequently targeted protein in each of the interactions. We further confirmed these results by determining the downstream targets of the identified signaling pathways (PI3K, Akt, FoxO1, Erk, and JNK). In conclusion, our study demonstrated that PI3K may play a central role in contacting and regulating the signaling pathways that contribute to bupivacaine-induced neurotoxicity.


Bacterial community dynamics and co-occurrence network patterns during different stages of biochar-driven composting.
Bacterial communities were dynamically tracked at four stages of biochar-driven sheep manure pile composting, and the co-occurrence networks with keystone taxa were established. The succession of bacterial community obvious varied during the composting process, Proteobacteria predominant in initial stage (39%) then shifted into Firmicutes in thermophilic (41%) and mesophilic (27%) stages, finally the maturation stage dominant by Bacteroidota (26%). Visualizations of bacterial co-occurrence networks demonstrate more cooperative mutualism and complex interactions in the thermophilic and mesophilic phases. Noticeably, the 7.5 and 10% biochar amended composts shown highest connections (736 and 663 total links) and positive cooperation (97.37 and 97.13% positive link) as well as higher closeness centrality and betweenness centrality of keystone taxa. Overall, appropriate biochar addition alters bacterial community succession and strengthens connection between keystone taxa and other bacteria, with 7.5 and 10% biochar amended composts has intense mutualistic symbiosis among bacterial communities.


Endothelial integrity of radial artery grafts harvested by minimally invasive surgery--immunohistochemical studies of CD31 and endothelial nitric oxide synthase expressions: a randomized controlled trial.
To compare the endothelial integrity of radial artery grafts harvested by minimally invasive surgery and arteries harvested conventionally for coronary artery bypass surgery (CABG) in 200 participants, who were assigned to interventions by using random allocation. An immunohistochemical procedure with monoclonal antibodies was employed to estimate CD31 antigen and endothelial nitric oxide synthase (eNOS) expressions - markers defining endothelial integrity. The CD31 immunostaining revealed that the endothelial cell integrity of the minimally invasive harvested arteries was preserved in 76.1±7.4% of the circumference of luminal endothelium, which was similar to results obtained in conventionally harvested grafts (77.2±9.8%; not significant). On the other hand, eNOS immunostaining indicated that the endothelial integrity of the minimally invasive harvested grafts was preserved in 75.4±10.5% while in conventionally harvested grafts it was reduced to 42.4±14.5% of the total luminal endothelium circumference (P<0.05). The endothelial integrity of radial artery grafts harvested by minimally invasive surgery is better preserved than in the grafts obtained by the conventional manner. This could play an important role in improving graft patency and might represent a preliminary condition of stable functioning in coronary arterial bypasses.


Speciation of phytate ion in aqueous solution. Cadmium(II) interactions in aqueous NaCl at different ionic strengths.
Interactions between myo-inositol 1,2,3,4,5,6-hexakis(dihydrogen phosphate) (phytic acid) and cadmium(II) were studied by using potentiometry (at 25 degrees C with the ISE-H+ glass electrode) in different metal to ligand (Phy) ratios (1:1< or =Cd(2+):Phy< or =4:1) in NaCl(aq) at different ionic strengths (0.1< or =I/mol L(-1)< or =1). Nine Cd(i)H(j)Phy((12-2i-j)-) species are formed with i=1 and 2 and 4< or =j< or =7; and trinuclear Cd3H4Phy2-. Dependence of complex formation constants on ionic strength was modeled by using Specific ion Interaction Theory (SIT) equations. Phytate and cadmium speciation are also dependent on the metal to ligand ratio. Stability of Cd(i)H(j)Phy((12-2i-j)-) species was modeled as a function of both the ligand protonation step (j) and the number of metal cations bound to phytate (i), and relationships found were used for the prediction of species other than those experimentally determined (mainly di- and tri-protonated complexes), allowing the possibility of modeling Phy and Cd(II) behavior in natural waters and biological fluids. A critical evaluation of phytate sequestering ability toward cadmium(II) has been made under several experimental conditions, and the determination of an empirical parameter has been proposed for an objective "quantification" of this ability. A thorough analysis of literature data on phytate-cadmium(II) complexes has been performed.


Invasion by an ecosystem engineer shifts the abundance and distribution of fish but does not decrease diversity.
Negative impacts of invasive species are widely accepted, but there is increasing evidence that neutral or positive effects are more prevalent than initially recognized, particularly for species which are of different functional / trophic group than the invader. We used a BACI design to examine how fish communities responded to the invasion of Halimeda incrassata, an ecosystem engineer which colonizes sandy habitats in the Western Mediterranean. While invasion did not alter overall species richness or diversity, we detected positive, negative and neutral responses by different fish species, which has important ecological and socio-economic implications. Contrasting responses likely result from different alterations that this alga conferred, putatively increasing prey availability via habitat creation, or limiting burial and camouflage abilities of fish. Our results highlight that effects of ecosystem engineers can be multiple and complex, and that predictions of invasive species are not straight forward.


Endoscopic evaluation by the Kyoto classification of gastritis combined with serum anti-Helicobacter pylori antibody testing reliably risk-stratifies subjects in a population-based gastric cancer screening program.
We previously demonstrated that the Kyoto classification of gastritis was useful for judging the status of Helicobacter pylori infection in a population-based screening program, and that adding H. pylori antibody test improved its accuracy (UMIN000028629). Here, we tested whether our endoscopic diagnosis of H. pylori infection status reliably estimated gastric cancer risk in the program. Data were collected from1345 subjects who underwent endoscopic follow-up 4 years after the end of the registration. We analyzed the association of three diagnostic methods of H. pylori infection with gastric cancer detection: (1) endoscopic diagnosis based on the Kyoto classification of gastritis; (2) serum diagnosis according to the ABC method (H. pylori antibody and pepsinogen I and II); and (3) endoscopic diagnosis together with H. pylori antibody test. During the follow-up, 19 cases of gastric cancer were detected. By Kaplan-Meier analysis, the detection rates of cancer were significantly higher in the past or current H. pylori infection groups than in the never-infected group with all 3 methods. By the Cox proportional hazards model, the hazard ratio for cancer detection was highest in evaluation with the combined endoscopic diagnosis and the antibody test (method 3; hazard ratio 22.6, 95% confidence interval 2.99-171) among the three methods (the endoscopic diagnosis (method 1); 11.3, 2.58-49.8, and the ABC method (method 2); 7.52, 2.49-22.7). Endoscopic evaluation of H. pylori status with the Kyoto classification of gastritis, especially combined with serum anti-Helicobacter pylori antibody testing, reliably risk-stratified subjects in a population-based gastric cancer screening program.


Effect of lergotrile on 3,4-dihydroxyphenylacetic acid (DOPAC) concentration and dopamine turnover in rat brain.
Lergotrile, a dopamine agonist, lowered whole brain DOPAC (3,4-dihydroxyphenylacetic acid) concentration in rats. At low doses down to 0.5 mg/kg of lergotrile mesylate, this effect occurred within 30 min, whereas at higher doses (20 mg/kg) the decline in DOPAC was delayed. The decrease in DOPAC persisted for several hours and presumably resulted from a compensatory decrease in brain dopamine turnover secondary to receptor stimulation by lergotrile. Other indications of decreased brain dopamine turnover after lergotrile included (a) a slower decline in dopamine concentration after synthesis inhibition by alpha-methyltyrosine, (b) a slower decline in alpha-methyl-m-tyramine, a false transmitter that is stored and released by dopamine neurons, and (c) a decreased accumulation of dopamine in response to gamma-butyrolactone, an agent that blocks firing and dopamine release by dopamine neurons. Lergotrile mesylate (20 mg/kg) also increased brain levels of 5-hydroxyindoleacetic acid and of 3-methoxy-4-hydroxyphenylethylene glycol sulfate, metabolites of serotonin and norepinephrine, respectively, and these increases were not antagonized by spiperone, a dopamine receptor antagonist.


Existence of SARS-Cov-2 in the Peritoneal Fluid.
To determine the existence of SARS-CoV-2 in the peritoneal fluid to assess the risk of exposure through surgical smoke and aerosolization threatening healthcare workers during abdominal surgery. SARS-CoV-2 is a respiratory virus and possible ways of viral transmission are respiratory droplets, close contact, and fecal-oral route. Surgeries pose risk for healthcare workers due to the close contact with patients. Aerosolized particles may be inhaled via the leaked CO2 during laparoscopic procedures and surgical smoke produced by electrocautery. All the data of 8 patients, who were tested positive for COVID-19, were collected between August 31, 2020 and April 30, 2021. Recorded clinicopathologic data included age, symptoms, radiological and laboratory findings, antiviral treatment before surgery, type of surgery and existence of the virus in the peritoneal fluid. Nasopharyngeal swab RT-PCR was used for the diagnosis. COVID-19 existence in the peritoneal fluid was determined by RT-PCR test as well. All 8 COVID-19 positive patients were pregnant, and surgeries were cesarean sections. 1 of the 8 patients was febrile during surgery. Also only 1 patient had pulmonary radiological findings specifically indicating COVID-19 infection. Laboratory findings were as follows: 4 of 8 had lymphopenia and all had elevated D-dimer levels. Peritoneal and amniotic fluid samples of all patients were negative for SARS-CoV-2. SARS-CoV-2 exposure due to aerosolization or surgical fumes does not seem to be likely, provided the necessary precautions are taken.


Unacylated ghrelin stimulates fatty acid oxidation to protect skeletal muscle against palmitate-induced impairment of insulin action in lean but not high-fat fed rats.
Ghrelin is a gut hormone that spikes in circulation before mealtime. Recent findings suggest that both ghrelin isoforms stimulate skeletal muscle fatty acid oxidation, lending to the possibility that it may regulate skeletal muscle's handling of meal-derived substrates. It was hypothesized in the current study that ghrelin may preserve muscle insulin response during conditions of elevated saturated fatty acid (palmitate) availability by promoting its oxidation. Soleus muscle strips were isolated from male rats to determine the direct effects of ghrelin isoforms on fatty acid oxidation, glucose uptake and insulin signaling. We demonstrate that unacylated ghrelin (UnAG) is the more potent stimulator of skeletal muscle fatty acid oxidation. Both isoforms of ghrelin generally protected muscle from impaired insulin-mediated phosphorylation of AKT Ser473 and Thr308, as well as downstream phosphorylation of AS160 Ser588 during high palmitate exposure. However, only UnAG was able to preserve insulin-stimulated glucose uptake during exposure to high palmitate concentrations. The use of etomoxir, an irreversible inhibitor of carnitine palmitoyltransferase (CPT-1) abolished this protection, strongly suggesting that UnAG's stimulation of fatty acid oxidation may be essential to this protection. To our knowledge, we are also the first to investigate the impact of a chronic high-fat diet on ghrelin's actions in muscle. Following 6 wks of a high-fat diet, UnAG was unable to preserve insulin-stimulated signaling or glucose transport during an acute high palmitate exposure. UnAG was also unable to further stimulate 5' AMP-activated protein kinase (AMPK) or fatty acid oxidation during high palmitate exposure. Corticotropin-releasing hormone receptor-2 (CRF-2R) content was significantly decreased in muscle from high-fat fed animals, which may partially account for the loss of UnAG's effects. UnAG is able to protect muscle from acute lipid exposure, likely due to its ability to stimulation fatty acid oxidation. This effect is lost in high-fat fed animals, implying a resistance to ghrelin at the level of the muscle. The underlying mechanisms accounting for ghrelin resistance in high fat-fed animals remain to be discovered.


TGF-ß isoforms in cancer: Immunohistochemical expression and Smad-pathway-activity-analysis in thirteen major tumor types with a critical appraisal of antibody specificity and immunohistochemistry assay validity.
The literature on TGF-ß in cancer including data on the expression or activation of TGF-ß pathway components in specific tumors types is steadily growing. However, no systematic and uniform analysis exists reporting expression levels of the main TGF-ß pathway components across the most frequent tumor types. We used a standardized immunohistochemical assay investigating TGF-ß isoform expression and pathway activation across 13 different tumor types and corresponding non-neoplastic tissues. The study was performed on tissue microarrays allowing for the parallel analysis of a total of 1638 human tumor samples. TGF-ß1, TGF-ß2 and p-Smad2/3 were substantially expressed in multiple cancers widening the options for TGF-ß isoform directed therapies. Of note, TGF-ß antigens appear to be expressed in an individual manner pointing towards a need for patient preselection for TGF-β isoform specific treatment. Yet, a thorough investigation of antibody specificity and assay validity revealed that immunohistochemistry did not correlate with other detection methods on mRNA or protein level in all instances. As such, with the currently available means (i.e. antibodies tested) a stratification of patients within clinical trials for TGF-ß directed antisense therapies based upon TGF-β immunohistochemistry alone has to be interpreted with caution and should be carefully evaluated in combination with other parameters.


Pelvic exenteration for advanced primary rectal cancer in male patients.
Between November 1987 and January 1996 pelvic exenteration for primary rectal cancer was carried out in 11 male patients. Two underwent a primary resection with subtotal cystectomy. In the remaining nine patients, the treatment commenced with a staging laparotomy and the fashioning of an end colostomy of the descending colon, followed by preoperative radiotherapy (50-56 Gy in 5 weeks). Total exenteration with uretero-ileo-cutaneostomy was carried out 4-6 weeks later. In two patients, the exenteration was performed despite the detection of hepatic metastases during the second laparotomy. The pathological staging was T4 in six and T3 in five patients. The immediate postoperative course was uneventful in eight patients and their hospital stay averaged 20 days. Serious postoperative complications prolonged the hospital stay of three patients. Three died during the first 6 months. Recurrent disease caused the death of three of the eight remaining patients: one locoregional (7.5 years after surgery), one from pre-existing hepatic metastases (18 months after surgery) and one from the combination of locoregional and distant recurrence (15 months after surgery). Four patients are on follow-up without evidence of disease, 96, 43, 23 and 22 months after surgery. One patient is alive 20 months after exenteration, with two pulmonary metastases having been recently excised. We conclude that, notwithstanding the morbidity rate, total pelvic exenteration is an acceptable option for advanced primary rectal cancer in male patients. Preoperative radiotherapy should be administered for cancers seated in the lower two-thirds of the rectum and perioperative chemotherapy should be considered seriously.


Fidelity of Motivational Interviewing in School-Based Intervention and Research.
Educational researchers and school-based practitioners are increasingly infusing motivational interviewing (MI) into new and existing intervention protocols to provide support to students, parents, teachers, and school administrators. To date, however, the majority of the research in this area has focused on feasibility of implementation rather than fidelity of implementation. In this manuscript, we will present MI fidelity data from 245 audio-recorded conversations with 113 unique caregivers and 20 coaches, who implemented a school-based, positive parenting intervention. The aggregate fidelity scores across coaches, parents, and sessions provide evidence the training and support procedures were effective in assisting school-based personnel to implement MI with reasonable levels of fidelity in practice settings. Further, results suggest that MI fidelity varied between sessions and coaches and that within-coach variation (e.g., session-level variation in the quality of MI delivered) greatly exceeded between-coach variation. Implications for practice and future research are discussed.


Nicotinamide attenuates the injury-induced decrease of hippocalcin in ischemic brain injury.
Nicotinamide is an important cofactor in the prevention of brain damage during focal cerebral ischemia. Hippocalcin is a calcium buffer protein that modulates intracellular calcium concentration and attenuates apoptosis. In this study, we investigated whether nicotinamide modulates hippocalcin expression during cerebral ischemia. Male Sprague-Dawley rats were treated with vehicle or nicotinamide (500 mg/kg) 2 h after the onset of middle cerebral artery occlusion (MCAO) and cerebral cortex tissues were collected 24 h after MCAO. Nicotinamide treatment decreased infarct volume in the cerebral cortex of MCAO-operated animals. Our proteomic approach revealed a decrease in hippocalcin expression in vehicle-treated animals during MCAO, which was attenuated by nicotinamide treatment. We used RT-PCR and Western blot analyses to demonstrate that nicotinamide clearly restored the injury-induced decrease in hippocalcin expression. Glutamate toxicity also decreased hippocalcin levels in cultured hippocampal cells, while nicotinamide treatment prevented the glutamate exposure-induced decrease in hippocalcin levels. These results suggest that nicotinamide modulates hippocalcin expression in cerebral ischemic injury and consequently contributes to the prevention of neuronal cell death.


Identification of MHC Class I bound peptides of Francisella tularensis Live Vaccine Strain using mass spectrometry.
Tularemia, a zoonosis generally prevalent in the northern half of the globe, is caused by Francisella tularensis. Among various Francisella tularensis species, subspecies tularensis is the most pathogenic to humans causing the infection through an airborne route, abrasions in the skin, and contact with infected animals. At present no approved vaccine exists for this intracellular pathogen. Principal defensive immunity against Francisella is T-cell mediated immunity, hence, picking out significant T-cell antigens is obligatory for Francisella vaccine advancement. In the present study, an immunoproteomics approach was employed to discover T-cell antigens by infecting dendritic cells derived from monocytes with F. tularensis NCTC10857, followed by immunoaffinity isolation of MHC class I molecules and acidic elution of bound peptides. The tandem mass spectrometry technique was used to identify the sequences of the isolated peptides. Ten MHC class I restricting Francisella derived peptides were successfully identified. Top three isolated peptide sequences were modeled and used for in silico docking study to substantiate their interaction and characterize their binding potential. Virtual docking studies further confirmed a high binding affinity for top three peptides with MHC class I molecule. The outcome of this study has led to identification of the probable vaccine candidates for human studies based on T cell-antigens against Francisella.


Synthesis of oxidative metabolites of CRA13 and their analogs: Identification of CRA13 active metabolites and analogs thereof with selective CB2R affinity.
CRA13; a peripheral dual CB1R/CB2R agonist with clinically proven analgesic properties, infiltrates into CNS producing adverse effects due to central CB1R agonism. Such adverse effects might be circumvented by less lipophilic compounds with attenuated CB1R affinity. Metabolism produces less lipophilic metabolites that might be active metabolites. Some CRA13 oxidative metabolites and their analogues were synthesized as less lipophilic CRA13 analogues. Probing their CB1R and CB2R activity revealed the alcohol metabolite 8c as a more potent and more effective CB2R ligand with attenuated CB1R affinity relative to CRA13. Also, the alcohol analogue 8b and methyl ester 12a possessed enhanced CB2R affinity and reduced CB1R affinity. The CB2R binding affinity of alcohol analogue 8b was similar to CRA13 while that of methyl ester 12a was more potent. In silico study provided insights into the possible molecular interactions that might explain the difference in the elicited biological activity of these compounds.


Long-term effect of interferon alpha-2b plus ribavirin therapy on incidence of hepatocellular carcinoma in patients with hepatitis C virus-related cirrhosis.
We assessed the efficacy of interferon (IFN) alpha-2b plus ribavirin therapy in patients with hepatitis C virus (HCV)-related cirrhosis, and elucidated the risk factors for the development of hepatocellular carcinoma (HCC) to determine whether these therapies might reduce the incidence of HCC. One hundred and thirty-two HCV-cirrhotic patients receiving IFN alpha-2b (3 or 5 MU thrice weekly) and oral ribavirin (1,000-1,200 mg/day) for 24 or 48 weeks were analysed. Cumulative incidence of HCC was estimated by the Kaplan-Meier method. The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log-rank test and by multivariate Cox's regression analysis. A total of 116 patients completed the treatment and 73 (55%) achieved a sustained virological response (SVR). Stepwise logistic regression analysis showed that nongenotype 1b (P < 0.001) and low viral load (P = 0.018) were independent variables of SVR. During a median follow-up period of 37 (12-63) months, HCC developed in 11 patients with non-SVR and five with SVR (P = 0.0178), whereas there was no difference between those with transient biochemical response and nonresponse (P = 0.5970). The Kaplan-Meier method also showed that old age (>or=60 years) (P = 0.0034) and genotype 1b (P = 0.0104) were associated with HCC occurrence. Using Cox's regression analysis, non-SVR (odds ratio = 3.521, P = 0.036), male (odds ratio = 6.269, P = 0.011) and old age (odds ratio = 3.076, P = 0.049) were independent significant risk factors contributing to HCC development. Our results suggest that achieving SVR by IFN alpha-2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV-related cirrhosis.


Key lessons learned from the immunization supply chain of Malawi, an African country using EVM2.0.
A country's immunization system's effectiveness depends on its supply chain's efficacy. To assess the challenges of maintaining an efficient vaccine supply chain, Malawi conducted its assessment using The EVM2.0 tool (Effective Vaccine Management). It is a cross-sectional study in which all EVM requirements were assessed between September and October 2021. Data were collected from eighty-two randomly selected sites using the site selection tool of the EVM. Data were entered into the EVM assessment tool 2.0 version 1.12 for analysis. This tool generates performance indicators and criteria scores for assessed sites, compared with a WHO minimum score of 80%. Overall criteria scores across all levels of the immunization supply chain showed a statistically significant mean difference of 5.92 (t = 2.58, P = 0.02). Comparative overall mean criteria scores across different levels of the immunization supply chain showed no statistically significant difference for primary (p = 0.76), sub-national (p = 0.69), and lowest distribution stores (p = 0.12). However, a substantial gap was found in the overall mean scores of the health facility's service point (SP) (t = 4.12, P = 0.001). The overall category scores across all immunization supply chain levels did not show a statistically significant difference. However, among individual category scores, Infrastructure (76 %), Equipment (67 %), Policies and procedures (62 %), Financial (47 %), and Resources (64 %) were found to be below the WHO minimum score. Though the 2021 Malawi EVM assessment findings are promising, they still identified the gaps to be improved to ensure the vaccine availability in the right amount, at the right time, and at the right cost.


Associations between substance use, neuropsychological functioning and treatment response in psychosis.
Relationships between substance use, severity of psychosis, and neuropsychological functioning were examined, together with their associations with treatment response and retention status. Participants included 477 people with psychosis (354 volunteers registered on a research database, and 123 enrolled in a treatment trial for substance misuse). Variables of primary interest included substance use history, course of psychotic disorder, and neuropsychological functioning on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Specific RBANS deficits were associated with a more chronic illness course. Compared to those with a stable or chronic course, younger people with a single episode of psychosis were more likely to have uncertain diagnoses, higher levels of substance use problems and variable neuropsychological functioning. History of substance use was not associated with additional overall neuropsychological deficits. Likewise, treatment retention and outcome were not associated with neuropsychological functioning. The findings suggest that, among people with co-existing psychotic and substance use disorders, response to cognitive-behaviour therapy is likely to be independent of neuropsychological functioning. Consideration should also be given to the potential use of neuropsychological assessments to assist differentiation of likely substance-associated psychosis from primary psychosis.


Methods for analyzing the role of phospholipase A₂ enzymes in endosome membrane tubule formation.
Cargo export from mammalian endosomal compartments often involves membrane tubules, into which soluble and membrane-bound cargos are segregated for subsequent intracellular transport. These membrane tubules are highly dynamic and their formation is mediated by a variety of endosome-associated proteins. However, little is known about how these membrane tubules are temporally or spatially regulated, so other tubule-associated proteins are likely to be discovered and analyzed. Therefore, methods to examine the biogenesis and regulation of endosome membrane tubules will prove to be valuable for cell biologists. In this chapter, we describe methods for studying this process using both cell-free, in vitro reconstitution assays, and in vivo image analysis tools.


"Demonstrating Masculinity" Via Intimate Partner Aggression: The Moderating Effect of Heavy Episodic Drinking.
The aim of the present study was to examine the mediational effect of masculine gender role stress on the relation between adherence to dimensions of a hegemonic masculinity and male-to-female intimate partner physical aggression. Men's history of heavy episodic drinking was also examined as a moderator of the proposed mediation effect. A sample of 392 heterosexual men from the southeastern United States who had been in an intimate relationship within the past year completed measures of hegemonic masculine norms (i.e., status, toughness, and antifemininity), masculine gender role stress, alcohol use patterns, and intimate partner physical aggression. Results indicated that the indirect effects of adherence to the antifemininity and toughness norms on physical aggression toward female intimate partners via masculine gender role stress were significant and marginal, respectively. A significant indirect effect of status was not detected. Moreover, subsequent analyses revealed that the indirect effects of antifemininity and toughness were significant only among men with a history of heavy episodic drinking. These findings suggest that heavy episodic drinking exacerbates a gender-relevant stress pathway for intimate partner aggression among men who adhere to specific norms of masculinity. Overall, results suggest that the proximal effect of heavy episodic drinking focuses men's attention on gender-based schemas associated with antifemininity and toughness, which facilitates partner-directed aggression as a means to demonstrate these aspects of their masculinity. Implications for the intersection between men's adherence to specific norms of hegemonic masculinity, cognitive appraisal of gender relevant situations, and characteristic patterns of alcohol consumption are discussed.


Chromatin during plant regeneration: Opening towards root identity?
Plants show exceptional developmental plasticity and the ability to reprogram cell identities during regeneration. Although regeneration has been used in plant propagation for decades, we only recently gained detailed cellular and molecular insights into this process. Evidently, not all cell types have the same regeneration potential, and only a subset of regeneration-competent cells reach pluripotency. Pluripotent cells exhibit transcriptional similarity to root stem cells. In different plant regeneration systems, transcriptional reprogramming involves transient release of chromatin repression during pluripotency establishment and its restoration during organ or embryo differentiation. Incomplete resetting of the epigenome leads to somaclonal variation in regenerated plants. As single-cell technologies advance, we expect novel, exciting insights into epigenome dynamics during the establishment of pluripotency.


Characterization of the deamidase enzyme responsible for the metabolism of the anticancer peptide: H-Arg-D-Trp-NmePhe-D-Trp-Leu-Met-NH2.
H-Arg-D-Trp-NmePhe-D-Trp-Leu-Met-NH2, a broad spectrum neuropeptide growth factor antagonist (antagonist G), is soon to enter a phase I clinical trial for the treatment of small-cell lung cancer (SCLC). The pre-clinical pharmacology of this peptide has revealed that its metabolism proceeds from the C-terminus via deamidation. In this study the class of enzyme responsible for the degradation of antagonist G has been characterized. Tissue distribution studies on the enzyme have shown it to be very widespread with high specific activity being detected in the spleen, kidney, H69 SCLC xenograft and liver (12.64, 9.58, 8.00 and 6.94 nmols G/mg protein/hr, respectively). HPLC gel filtration indicated that the G-deamidase enzyme had an apparent molecular mass of 81 kDa. The sub-cellular distribution of the enzyme using differential centrifugation indicates that it is largely soluble with > 85% of the activity located in the cytosolic fraction. The distribution of activity towards antagonist G closely resembles that of esterase and acid carboxypeptidase activity, two activities, along with deamidase activity, known to be possessed by serine carboxypeptidases. Studies using a range of protease inhibitors showed clear inhibition of metabolism by phenylmethylsulphonylfluoride and benzyloxycarbonylphenylalanine chloromethylketone, indicating that the enzyme is a chymotrypsin-like serine carboxypeptidase. This knowledge of the enzyme will be invaluable in the further development of antagonist G and similar compounds. Moreover, the widespread distribution of this enzyme together with its broad specificity for C-terminal group suggests that it should be given serious consideration when designing C-terminally modified peptide drugs.


Metabolomics Approaches for Analyzing Effects of Geographic and Environmental Factors on the Variation of Root Essential Oils of Ferula assa-foetida L.
Environmental factors shape the production and accumulation processes of plant secondary metabolites in medical and aromatic plants and thus their pharmacological and biological activity. Using an environmental metabolomics approach, we determined chemotypes and specific compounds on the basis of essential oils (EOs) from roots of 10 Iranian Ferula assa-foetida L. populations and related them to geographical, climate, and edaphic data. GC-MS revealed three distinct chemotypes characterized by (I) monoterpenes and Z-1-propenyl sec-butyl disulfide; (II) eudesmane sesquiterpenoids and α-agarofuran; and (III) Z- and E-1-propenyl sec-butyl disulfide. NIRS measurements indicated a similar but less distinct pattern. Structural equation models showed that EO constituents and content were directly influenced by edaphic factors (texture, pH, and iron, potassium, and aluminum content) and temperature and predominantly indirectly by latitude, longitude, and altitude. Predicting EO constituents or chemotypes by geographical, climate, and soil factors can be used in F. assa-foetida to select populations with specific EO characteristics.


Quantitative endoscopic classification of esophagitis by means of computerized image processing. Part 1: Theoretical background.
The potential sources of error for quantitative mapping of pathological areas in tubular organs are investigated mathematically and discussed. The first of the main errors stems from a predominance of red in the illuminating light reflected and re-reflected from the side wall of the tubular organ as compared with the white illuminating light coming directly from the light source in the endoscope. A mathematical model for this has been constructed to define an allowed interval of observation distance. The second error is due to geometrical projection, and results from the fact that more distant parts of the inside of a tube subtends a smaller solid angle than closer parts.


Nonmetallic SERS-based biosensor for ultrasensitive and reproducible immunoassay of ferritin mediated by magnetic molybdenum disulfide nanoflowers and black phosphorus nanosheets.
To improve the curability of cancer patients, it is essential to propose an early diagnosis technology with ultra-high sensitivity and reliable biocompatibility. Herein, a sophisticated nonmetallic SERS-based immunosensor, comprised by a MoS2 @Fe3O4 nanoflower-based immunoprobe with magnetism and a black phosphorus (BP) nanosheet-based immunosubstrate, was proposed for the specific in-situ monitoring of ferritin (FER). The sandwich immunosensor was endowed with an excellent SERS performance mainly ascribed to a synergistic chemical enhancement as well as an additional electrostatic adsorption effect, achieving a limit of detection down to 7.3 × 10-5 μg/mL. Particularly, all the Raman label, target FER, and anti-FER could be completely degraded within 70 min under visible light irradiation owing to the favorable photocatalytic activities of MoS2 and BP which could be then effectively separated and collected with the assistance of an external magnet. Such a recyclable nonmetallic immunosensor holds great potential and practicality in the clinical screening of cancer.