Preferential growth of metastatic tumors at the pleural surface of mouse lung.
In an experimental model of lung metastasis we have observed that more metastatic tumors are located on the pleura of the lung than in the parenchyma. To study possible reasons for this differential pattern we have now related the initial distribution of injected tumor cells to the later location and growth rate of metastases in different regions of the lung in C57bl/6 mice. It was found that labeled murine fibrosarcoma cells were evenly distributed throughout the lungs 24 h after intravenous injection into controls and animals previously treated with bleomycin or by exposure to hyperoxia. These treatments, known to induce pulmonary endothelial injury, were associated with increased tumor cell localization in the lung. In all cases, using morphometric methods, we found that after 2 weeks, approximately 75 per cent of metastatic tumors were located at the pleura. By [3H]thymidine labeling in autoradiographs, pleural tumors in all experimental groups had a growth rate 14 times the growth rate of tumors located in the internal regions of the lung. In vitro, the fibrosarcoma cells proliferated more rapidly on connective tissue matrices prepared from normal pleuras than they did on matrices from the remainder of the lung. Protease digestion of these matrices indicated differences in composition with more insoluble collagen, probably type I collagen, present at the pleura. These data suggest that, in spite of the initial random distribution and localization of tumor cells in the lung, there is preferential growth of metastatic tumors at the pleura which may be related to regional differences in the composition of the extracellular matrix.


Phosphatidylcholine-depleted lecithin: A clean-label low-HLB emulsifier to replace PGPR in w/o and w/o/w emulsions.
In contrast to when polyglycerol polyricinoleate (PGPR) is used as lipophilic emulsifier, the used oil phase and phospholipid composition have a strong influence on the characteristics of water-in-oil (w/o) emulsions prepared using lecithin. These parameters are also expected to influence the characteristics of the corresponding water-in-oil-in-water (w/o/w) emulsions. Moreover, a hydrophilic emulsifier is typically added to the external water phase of w/o/w emulsions and is also expected to influence the characteristics of the w/o/w emulsions. Lecithin with a varying phospholipid composition was used to prepare w/o emulsions with medium chain triglyceride (MCT) oil as well as long chain triglyceride (LCT) oil. In case the w/o emulsion was stable, w/o/w emulsions were produced as well. Hereby, the w/o/w emulsions were prepared using different hydrophilic emulsifiers. Each of the lecithin samples could be used to produce a stable w/o emulsion in MCT-oil. In contrast, a stable w/o emulsion could only be produced in LCT-oil with phosphatidylcholine depleted lecithin. The storage stability of the w/o/w emulsions was also higher in case MCT-oil was used as compared to LCT-oil. Finally, a remarkable influence of the high-HLB emulsifier on the resulting enclosed water volume fraction in the w/o/w emulsions was observed.


Progress on Regulation of NLRP3 Inflammasome by Chinese Medicine in Treatment of Ulcerative Colitis.
Ulcerative colitis (UC) is a chronic, non-specific intestinal disease that not only affects the quality of life of patients and their families but also increases the risk of colorectal cancer. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome is an important component of inflammatory response system, and its activation induces an inflammatory cascade response that is involved in the development and progression of UC by releasing inflammatory cytokines, damaging intestinal epithelial cells, and disrupting the intestinal mucosal barrier. Chinese medicine (CM) plays a vital role in the prevention and treatment of UC and is able to regulate NLRP3 inflammasome. Many experimental studies on the regulation of NLRP3 inflammasome mediated by CM have been carried out, demonstrating that CM formulae with main effects of clearing heat, detoxifying toxicity, drying dampness, and activating blood circulation. Flavonoids and phenylpropanoids can effectively regulate NLRP3 inflammasome. Other active components of CM can interfere with the process of NLRP3 inflammasome assembly and activation, leading to a reduction in inflammation and UC symptoms. However, the reports are relatively scattered and lack systematic reviews. This paper reviews the latest findings regarding the NLRP3 inflammasome activation-related pathways associated with UC and the potential of CM in treating UC through modulation of NLRP3 inflammasome. The purpose of this review is to explore the possible pathological mechanisms of UC and suggest new directions for development of therapeutic tools.


Thyroid carcinoma in Pendred's syndrome.
A case of Pendred's syndrome is reported. One year after subtotal removal of a simple adenomatous colloid goitre, the patient presented with a follicular thyroid carcinoma with invasive growth through the capsule into the surrounding muscular tissue and vascular invasion.


Survey of inappropriate use of magnetic resonance imaging.
There are concerns that not all costly advanced imaging is appropriate. However, studies about the appropriateness of magnetic resonance imaging (MRI) are sparse. The aim of this study was to review various MRI examinations done at a university hospital to determine whether there is inappropriate use. Altogether 150 common MRIs (upper abdomen or liver, lumbar spine, knee, head and head of children performed under anaesthesia, 30 each) were reviewed consecutively. The referrals and corresponding patient files were analysed by senior radiologists and the indications of the examinations were compared to the referral criteria. Seven per cent of the examinations were deemed inappropriate. All the MRIs of the head done on children were indicated. One to three examinations in all other subgroups were not indicated. The most common appropriate indications were ambiguous hepatic, pancreatic or adrenal lesions, prolonged lower back pain, suspicion of meniscus rupture, brain malignancy and developmental disorder of a child, respectively. Although the proportion of inappropriate examinations was not high; financial issues and the growing number of patients referred for MRI are of concern. Education and regular use of up-to-date referral guidelines could help to further improve appropriateness. •Seven per cent of the MRI examinations analysed were inappropriate at a university hospital. •Everyday practices of a hospital may contribute to the level of appropriateness. •A survey of indications for previous MRI examinations might be helpful in various institutions.


Three New Labdane-Type Diterpenoids from the Fruits of Amomum villosum and Their Anti-Inflammatory Activities.
Three new labdane-type diterpenoids, calcaratarin E, villosumtriol, and 12-epi-villosumtriol (1-3) were isolated from the fruits of Amomum villosum, along with seven known diterpenoids (4-10). Through comprehensive analysis of chemical evidence and spectral data including UV, 1D and 2D NMR, HR-ESI-MS, IR, and X-ray crystallography, the structures of these novel compounds were successfully determined. Additionally, the inhibitory effects of compounds 2-10 on NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells were evaluated. Notably, compound 6 exhibited the most significant inhibitory effect with an IC50 value of 1.74±0.69 μM.


[Agreement in asthmatics' perception of dyspnea during acute and chronic obstruction].
Three types of asthmatic patients can be identified during periods of clinical stability: "poor perceivers," "normal perceivers," and "over perceivers." When asthmatics undergo bronchial challenge in the laboratory, the same distinctions in type of perception can be observed. The aim of the present study was to determine the level of agreement between the 2 situations. A total of 93 patients with persistent moderate asthma (36 men and 57 women; mean age 40 years) were studied. We asked them to assess their dyspnea on a modified Borg scale when stable and after each histamine dose in a bronchial provocation test. When a patient's Borg scale assessment in stable situation was below the 25th percentile, that patient was classified as a poor perceiver. Patients were considered over perceivers if their score in stable situation was in the 75th percentile. Others were labeled normal perceivers. Type of perception during acute bronchoconstriction was defined in function of the change in Borg assessment once forced expiratory volume in the first second had decreased 20%: poor perceivers were those whose change in Borg assessment was in the 25th percentile, over perceivers were in the 75th percentile, and normal perceivers in the middle percentiles. In stable situation, 23 patients were poor perceivers, 58 were normal perceivers, and 12 were over perceivers. During bronchoconstriction, there were 23 poor perceivers, 47 normal perceivers, and 23 over perceivers. Agreement was estimated by a kappa index of 0.0574 for poor perception, 0.1521 for over perception, and 0.3980 for normal perception. Asthmatics' perception of dyspnea during periods of stability and during acute bronchoconstriction are independent phenomena. It is therefore not possible to infer how a patient will perceive an asthmatic attack by evaluating only how he or she perceives breathlessness during stable periods.


Co-encapsulation of (-)-epigallocatechin-3-gallate and quercetin in double emulsion hydrogel beads: Microstructures, functional properties, and digestion behaviors.
Co-loaded (-)-epigallocatechin-3-gallate (EGCG) and quercetin double emulsions and hydrogel beads were prepared, and their structure, functions, and digestion characteristics were investigated. The double emulsion particles were adsorbed by the cross-linked chains of the hydrogel beads. The encapsulation efficiencies of EGCG and quercetin within the hydrogel beads were higher than those within the double emulsion, while the antioxidant activities of the double emulsions were higher than those of the hydrogel beads. A lower amount of free fatty acids (FFAs) was released from the hydrogel beads than that released from the double emulsions. The bioavailability of EGCG was higher in the hydrogel beads than those in the double emulsions, while the quercetin bioavailability was not significantly different expect for the ratio of 3:7. The hydrogel beads remained intact in the stomach; however, numerous oil spills occurred in the small intestine. These data may improve double-emulsion-based delivery systems for controlled lipolysis and the release of co-encapsulated hydrophilic and lipophilic bioactive compounds.


Temporal structure of variability decreases in upper extremity movements post stroke.
The objective of this study was to determine movement variability in the more-affected upper-extremity in chronic stroke survivors. We investigated two hypotheses: (1) individuals with stroke will have increased amount of variability and altered structure of variability in upper-extremity joint movement patterns as compared to age-matched controls; and (2) the degree of motor impairment and joint kinematics will be correlated with the temporal structure of variability. Sixteen participants with chronic stroke and nine age-matched controls performed three trials of functional reach-to-grasp. The amount of variability was quantified by computing the standard deviation of shoulder, elbow, wrist and index finger flexion/extension joint angles. The temporal structure of variability was determined by calculating approximate entropy in shoulder, elbow, wrist and index finger flexion/extension joint angles. Individuals with stroke demonstrated greater standard deviations and significantly reduced approximate entropy values as compared to controls. Furthermore, motor impairments and kinematics demonstrated moderate to strong correlations with temporal structure of variability. Changes in the temporal structure of variability in upper-extremity joint angles suggest that movement patterns used by stroke survivors are less adaptable. This knowledge may yield additional insights into the impaired motor system and suggest better interventions that can enhance upper-extremity movement adaptability.


Examining the Role of Body Image Instability in Young Adult Women: Conceptualization, Development, and Psychometric Evaluation of the Vacillating Body Image Scale (VBIS).
The current study conceptualized body image instability as a maladaptive tendency to vacillate between different self-perceptions of one's overall body image and developed a corresponding measure to assess body image instability. Results from a series of studies of young adult women demonstrated the validity, reliability, and utility of the Vacillating Body Image Scale (VBIS) as a meaningful measure of body image instability. In Study 1, we found that body image instability, as assessed by the VBIS, represents a unidimensional and reliable construct. In Study 2, we found evidence for both the convergent and discriminant validity of the VBIS in relation to other individual differences measures (i.e., self-concept schema, broad personality factors). In Study 3, the concurrent criterion validity of the VBIS was supported for young adult women in relation to a range of adjustment measures. Finally, in Study 4, we found consistent evidence for the incremental validity of the VBIS in predicting subsequent variations in eating disturbances, even after controlling for global self-esteem and self-concept instability. Overall, our findings offer promising support for our contention that body image instability, as measured by the VBIS, represents an important construct for understanding eating-related disturbances and other health outcomes in young adult women.


"I'm a Horrible Mother": The Relationship Between Psychoeducation, Disclosure, and Shame Surrounding Postpartum Intrusive Thoughts.
The current study explored whether women who had experienced Postpartum Intrusive Thoughts of Intentional Harm (PPITIH) were more likely to disclose these thoughts and less likely to experience shame about such thoughts after being exposed to psychoeducation about PPITIH. The study also examined whether shame was a significant predictor of the number of people to whom the participant had disclosed their PPITIH. Additionally, a content analysis was used to explore participants' responses to the psychoeducation. One hundred and thirty-nine women completed the web-based study. The number of participants reporting PPITIH significantly increased following the exposure to the psychoeducation and participants' levels of shame significantly decreased. No relationship was found between participants' level of shame and the number of people to whom they had disclosed their experiences with PPITIH prior to the study. Themes of relatability, reassurance, and resonance emerged from the responses of participants who reported having experienced PPITIH; whereas those of surprise/sadness/shock and similarities emerged from those who denied having experienced them.


Apnea testing: the effects of insufflation catheter size and flow on pressure and volume in a test lung.
The apnea test is used to determine the absence of respiratory drive when determining brain death. Current guidelines for performing the apnea test do not specify the size of insufflation catheter (IC) to use with each endotracheal tube (ETT) size, despite case reports describing procedure-related complications with the use of various IC sizes. We studied the effect of the ratio of IC outer diameter to ETT inner diameter on the pressure and volume generated within the lungs during the apnea test. We tested ETTs with inner diameters of 6.0-10.0 mm, IC outer diameters of 10-16 French, and oxygen-supply tubing, at oxygen flows of 6-15 L/min, in an intubation manikin connected to a test lung. The multivariate analysis of variance method identified significant differences in the pressures and volumes during the apnea test (P < .001), and the Tukey method identified significant differences in the pressures and volumes associated with IC/ETT ratios ≥ 0.7 and < 0.7 (P < .05). An IC with an outer diameter < 70% of the ETT inner diameter, at 6 L/min, may prevent inappropriate lung pressure and volume during the apnea test. This recommendation, coupled with current American Academy of Neurology guidelines for the determination of brain death, may reduce the risk of procedure-related complications.


Association of candidate genes (ALR2, RAGE, and VEGF) polymorphisms with diabetic retinopathy in type 2 diabetic patients of Khyber Pakhtunkhwa, Pakistan.
To evaluate the aldose reductase (ALR2, rs759853), receptor for advanced glycation end products (RAGE, rs2070600), and vascular endothelial growth factor (VEGF, rs833061) association with diabetic retinopathy in type 2 diabetic patients of Khyber Pakhtunkhwa population. A case-control study was conducted on a total of 550 subjects consisting of 186 with diabetic retinopathy (DR) having type 2 diabetes, 180 had type 2 diabetes (T2DM), and 184 healthy controls (HC). All the samples were subjected to DNA isolation using salting-out method followed by SNP genotyping through Tetra-ARMS PCR. Chi square and Exact Fischer tests were used for alleles and genotypes distribution. Odd ratio and confidence interval values were found out by online software Medcalc Odd ratio Calculator. Multiple parameters such as random blood sugar (RBS) (p < 0.001), fasting blood sugar (FBS) (p < 0.001), HbA1c (p < 0.001), total cholesterol (p < 0.001), LDL (p < 0.001), HDL (p < 0.001), BMI (p < 0.001) and hypertension (p = 0.018) exhibited strong association with DR as compared to DM and HC. Our results displayed that the VEGF-rs833061 and RAGE- rs2070600 exhibited significant association (p < 0.05) with an increased DR risk, when compared with T2DM. In contrast, ALR2 didn't display association with DR (p > 0.05) when compared with T2DM, but showed association (p < 0.05) when compared with HC. Statistically significant association was observed in VEGF-rs833061 and RAGE-rs2070600 with DR in type 2 diabetic patients. While, ALR2- rs759853 didn't exhibit significant association with DR. This is the first study to report the association of candidate genes (ALR2, VEGF and RAGE) with DR in type 2 diabetes of Khyber Pakhtunkhwa population. More similar research studies are recommended with larger data sets in other ethnicities both national and international.


Effect of prolonged thienopyridine use after drug-eluting stent implantation (from the TAXUS landmark trials data).
Previous observational studies have evaluated the utility of prolonged thienopyridine therapy in patients receiving drug-eluting stents, with conflicting results. A landmark analysis was therefore performed on the basis of the prospective, double-blind TAXUS-II SR, TAXUS-IV, and TAXUS-V trials. Of 2,736 randomized patients, 2,171 were event free at 1 year, of whom 964 (44.4%) at physician discretion were still taking thienopyridines at that time. Among the 1,141 event-free patients randomized to Taxus stents, a trend was present in those patients still taking compared with those having discontinued thienopyridines at 1 year to have numerically fewer very late stent thrombosis episodes at 2 years (0 vs 4 [0.7%] events, respectively, p = 0.07) and 5 years (4 [0.8%] vs 8 [1.4%] events, respectively, p = 0.43). However, in event-free Taxus patients taking compared with those not taking thienopyridines at 1 year, there were no significant differences in the 2- and 5-year rates of death (1.4% vs 0.6%, p = 0.22, and 6.0% vs 7.4%, p = 0.83, respectively) and death or myocardial infarction (1.8% vs 1.9%, p = 0.82, and 8.3% vs 9.8%, p = 0.75, respectively). There were no significant interactions between 1-year thienopyridine use status and stent type (Taxus vs bare-metal stent) on the individual or composite end points of stent thrombosis, death, or myocardial infarction at either 2 or 5 years (all interaction p values >0.50). In conclusion, thienopyridine use beyond 1 year after drug-eluting stent implantation may reduce stent thrombosis over the subsequent 12-month period, but the rates of death and myocardial infarction at 2 and 5 years are not prevented by extended thienopyridine use after either drug-eluting or bare-metal stent implantation.


Sexual Violence in Women with HIV Positive Spouse and Their Mental Health.
Sexual violence (SV) against women is one of the most important issues in women's health. We aimed to investigate the related variable for SV against women with HIV spouse and its relationship with mental problems in them. A cross-sectional study. This study was performed on 143 women referred to Hamadan and Malayer Risky Behavior Related Disease Clinic (Triangular Clinic), located in Comprehensive Health Service centers, Iran in 2019. SV and mental problems were assessed using standard questionnaires, based on interview. All analyses performed using SPSS. The significance level of all analyses was considered 0.05. Totally, 407 HIV+ patients were diagnosed from 1998 to 2018, in Hamadan and Malayer cities. We assessed the wives of survivors who allowed about SV. Mean of SV in women with HIV positive spouse was significantly higher than control group (P=0.004). Among all variables, unsafe sex, extramarital relationship, smoking, alcohol, multi-partner and suicide were significantly related to SV; but age, living area, educational status, income and job in both men and women had not statically significant relationship with SV. SV besides its complications and mental problems in women with HIV positive spouses must be considered in interventional programs in order to improve sexual rights in this vulnerable group in the future.


Systemic inflammation and insulin sensitivity in obese IFN-γ knockout mice.
Adipose tissue macrophages are important mediators of inflammation and insulin resistance in obesity. IFN-γ is a central regulator of macrophage function. The role of IFN-γ in regulating systemic inflammation and insulin resistance in obesity is unknown. We studied obese IFN-γ knockout mice to identify the role of IFN-γ in regulating inflammation and insulin sensitivity in obesity. IFN-γ-knockout C57Bl/6 mice and wild-type control litter mates were maintained on normal chow or a high fat diet for 13 weeks and then underwent insulin sensitivity testing then sacrifice and tissue collection. Flow cytometry, intracellular cytokine staining, and QRTPCR were used to define tissue lymphocyte phenotype and cytokine expression profiles. Adipocyte size was determined from whole adipose tissue explants examined under immunofluorescence microscopy. Diet-induced obesity induced systemic inflammation and insulin resistance, along with a pan-leukocyte adipose tissue infiltrate that includes macrophages, T-cells, and NK cells. Obese IFN-γ-knockout animals, compared with obese wild-type control animals, demonstrate modest improvements in insulin sensitivity, decreased adipocyte size, and an M2-shift in ATM phenotype and cytokine expression. These data suggest a role for IFN-γ in the regulation of inflammation and glucose homeostasis in obesity though multiple potential mechanisms, including effects on adipogenesis, cytokine expression, and macrophage phenotype.


Loading of Cefixime to pH sensitive chitosan based hydrogel and investigation of controlled release kinetics.
Chitosan (biopolymer) and polyvinyl pyrolidone (PVP) with aminopropyletriethoxy silane (cross linker) based hydrogels were prepared and tested for controlled drug release. The drug release and kinetics were studied as a function of pH. Formulations were characterized by Fourier Transform Infrared (FTIR) and Thermogravimetric (TGA) analysis and TAP 32 hydrogel formulation was the most stable and hydrogel samples showed promising antibacterial activity against E. coli strain. The maximum swelling (4386%) was observed for TAP 32 formulation in distilled water, which was decreased with the concentration of ions. The diffusion exponent (n) values of all hydrogel formulations were recorded to be <0.5, which is an indication of Quasi-Fickian diffusion. The maximum swelling was observed at pH 2 and decreased at higher pH. The pH sensitivity of hydrogels found to be promising for their use in drug delivery, which was tested for cefixime drug. Drug release of 81.6% was observed for the period of 12 h in a simulated gastric fluid (SGF). The values of R2 for zero order, first order, Higuchi, Hixson, Korsmeyer-Peppas and Baker-Lonsdale were 0.97, 0.9818, 0.99, 0.99, 0.88 and 0.80, respectively. The hydrogels based on chitosan and PVP revealed potential for controlled cefixime drug release in gastric pH medium.


Repeated assessment of coronary flow velocity pattern in patients with first acute myocardial infarction.
The aim of this study was to evaluate the coronary blood flow velocity pattern immediately and 24 h after percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI) in relation to myocardial reperfusion and follow-up left ventricular (LV) function. Analysis of coronary blood flow velocity pattern after AMI may provide information about microvascular damage and the occurrence of a reperfusion injury. Measurement of coronary blood flow velocity pattern was performed immediately after PTCA and after 24 h in 25 patients with first AMI using a Doppler guidewire. Measurements were related to reperfusion determined by intravenous myocardial contrast echocardiography (MCE) performed before PTCA and at 24 h and to LV function at four weeks. Using MCE, 13 patients showed reperfusion and 12 patients showed nonreperfusion. Compared with patients with reperfusion, patients with MCE nonreperfusion had a lower systolic peak flow velocity immediately after PTCA (10.0 +/- 0.3 cm/s vs. 19.3 +/- 0.8 cm/s, respectively) and after 24 h (12.3 +/- 0.4 cm/s vs. 21.3 +/- 0.1 cm/s, respectively, p = 0.0022), more frequent early systolic retrograde flow (6/12 vs. 0/13, p = 0.0052 immediately after PTCA and 24 h later) and a shorter diastolic deceleration time immediately after PTCA (483 +/- 6 ms vs. 737 +/- 0 ms, respectively) and after 24 h (551 +/- 9 ms vs. 823 +/- 2 ms, respectively, p = 0.0091). Similarly, patients with impaired LV function at four weeks had altered coronary flow pattern compared with patients with preserved function. The coronary flow velocity pattern showed a tendency for improvement after 24 h in the reperfusion and the nonreperfusion groups. The coronary flow velocity pattern immediately and 24 h after PTCA for AMI relates to myocardial perfusion determined by MCE and LV function at four weeks. The flow velocity pattern shows slight improvement during the first 24 h after revascularization, indicating the absence of a major reperfusion injury.


Comparison of faecal Lactobacillus populations in experimental animals from different breeding facilities and possible consequences for probiotic studies.
The effect of probiotic lactobacilli is likely dependent on the indigenous Lactobacillus strains in the intestinal tract. Since a substantial number of probiotic studies is performed in rodents, we compared the Lactobacillus strains of different rat and mouse populations in three animal facilities. SDS-PAGE and 16S rDNA analysis of cultured faecal lactobacilli revealed that different Lactobacillus strains were detected in genetically similar Wistar rats bred at different locations. Further, within the same animal facility host genetics did not affect the types of the predominant lactobacilli strains. Our results show that the environmental background of laboratory animals rather than host genetics determines the indigenous Lactobacillus strains that are found. Our findings underline the importance of microflora analysis in probiotic studies.


In silico fragment-based discovery of indolin-2-one analogues as potent DNA gyrase inhibitors.
We describe here the fragment-based design of potent DNA gyrase inhibitors. Using the tools of virtual screening and NMR spectroscopy we identified the binding of two low-molecular weight fragments (2-aminobenzimidazole and indolin-2-one) to the 24kDa N-terminal fragment of DNA gyrase B. Further in silico optimization of indolin-2-one led to the discovery of potent DNA gyrase inhibitors.


Ischemic acute renal failure in the rat: effects of L-arginine and superoxide dismutase on renal function.
Regulation of renal hemodynamics -- especially intraglomerular hemodynamics -- is closely related to the L-arginine (L-Arg)/nitric oxide (NO) pathway, both under basal conditions and in acute renal failure (ARF). Also, superoxide anions -- which may react with NO -- play a role in ischemic ARF. L-Arg not only has beneficial effects on glomerular filtration rate (GFR) but also reduces O2(-) production and prevents NO synthase isoform I up-regulation. Thus, it is of interest to elucidate whether the potential beneficial effects of L-Arg in reperfusion can be augmented by additional treatment with superoxide dismutase (SOD). ARF was induced by renal artery clamping for 40 minutes. Animals were treated with either L-Arg, SOD, a combination of both, or saline. GFR, renal plasma flow (RPF), filtration fraction (FF) and blood pressure were recorded at baseline, after induction of ARF, during drug infusion and thereafter. Renal artery clamping induces a severe drop of GFR, RPF and FF, which all are improved by L-Arg and SOD. Increasing GFR is mainly due to better renal perfusion. FF fell after reperfusion and increased with L-Arg and SOD, indicating improvement of disturbed intrarenal hemodynamics. Combined administration of L-Arg and SOD showed similar effects in comparison with each substance alone, but did not induce additional effects on GFR and RPF. L-Arg and SOD exert beneficial effects in ischemic ARF. Probably, improvements in reducing NO availability and in enhancing O2(-) formation are both playing a mediating role. The underlying mechanisms regulating the interplay between NO availability and O2(-) formation need to be elucidated in further studies using -- aside from other means -- selective NOS inhibitors, intervention in different experimental phases and treatment for a longer period.


The role of free fatty acids in the regulation of lipolysis by human adipose tissue cells.
The effect of added fatty acid on lipolysis and cyclic AMP concentration of human adipose tissue cells was studied. The addition of sodium oleate decreased the lipolytic response of adipocytes to 10(-7) M isoproterenol. Inhibition was detectable with the lowest quantity of oleate added, 0.2 mM, and was progressively greater with increasing quantities of added fatty acid. Palmitic and linoleic acids were as effective as oleic acid in suppressing isoproterenol-stimulated lipolysis. Suppression of cyclic AMP formation was detectable within one minute after the addition of oleate. Cyclic AMP formation, suppressed by accumulated fatty acids, could not be stimulated by the addition of fresh isoproterenol. However, after the accumulated fatty acids were removed by buffer change, cyclic AMP formation was stimulated by fresh isoproterenol. These findings are consistent with the view that fatty acids are physiologically significant regulators of lipolysis.


A role of color vision in emmetropization in C57BL/6J mice.
Spectral composition affects emmetropization in both humans and animal models. Because color vision interacts the effects of chromatic defocus, we developed a method to bypass the effects of longitudinal chromatic aberration by placing a spectral filter behind the optics of the eye, using genetic tools. Newborn C57BL/6J (B6) mice were reared in quasi-monochromatic red (410-510 nm) or blue (585-660 nm) light beginning before eye-opening. Refractive states and ocular dimensions were compared at 4, 6, 8, and 10 weeks with mice reared in normal white light. Cre recombinase-dependent Ai9 reporter mice were crossed with Chx10-Cre to obtain Chx10-Cre;Ai9 mice, expressing red fluorescent protein in retinal Cre-positive cells. Ai9 offsprings, with and without Cre, were reared under a normal visual environment. Refraction and axial components were measured as described above. Expression levels of M and S opsin were quantified by western blotting at 10 weeks. Compared with those reared in white light, B6 mice reared in red light developed relative hyperopia, principally characterized by flattening of corneal curvature. Emmetropization was not affected by blue light, possibly because the reduction in vitreous chamber depth compensated for the increase in corneal curvature. Compared with Cre-negative littermates, the refraction and axial dimensions of Chx10-Cre;Ai9 mice were not significantly different at the follow-up timepoints. M opsin levels were higher in Chx10-Cre;Ai9 mice at 10 weeks while S opsin levels were not different. Red light induced a hyperopic shift in mouse refractive development. Emmetropization was not impacted in mice with perturbed color vision caused by intrinsic red-fluorescent protein, suggesting that color vision may not be necessary in mouse emmetropization when other mechanisms are present.


The application of region-specific probes for the resolution of duplication 8p: a case report and a review of the literature.
The structural rearrangement in the short arm of a chromosome 8 in a clinically affected patient has been reinvestigated by FISH using whole chromosome painting and region specific YAC probes. An inverted duplication of the segment p22-->p11.2 and a deletion of the subtelomeric region were demonstrated. By this approach, a more detailed resolution of the duplication/deletion 8p was possible. With the application of molecular cytogenetic methods the existence of different duplication segments within the clinical entity of duplication/deficiency 8p can be shown.


Transcatheter Versus Rapid-Deployment Aortic Valve Replacement: A Propensity-Matched Analysis From the German Aortic Valve Registry.
This study sought to compare patient characteristics, procedural outcomes, and valve hemodynamics of surgical aortic valve replacement (SAVR) with current-generation rapid-deployment valves (RDVs) versus transcatheter aortic valve replacement (TAVR) with current-generation transcatheter heart valves (THVs). The patient population currently treated with RDVs may have potential similarities with the current TAVR population, but comparative studies in a large patient population remain scarce. A total of 16,473 patients who underwent isolated SAVR using current-generation RDVs or isolated transfemoral TAVR with current-generation THVs between 2011 and 2017 were enrolled into the German Aortic Valve Registry. Baseline, procedural, and in-hospital outcome parameters were analyzed for RDVs and THVs before and after 1:1 propensity score matching. Furthermore, RDVs and THVs with similar design characteristics were compared with each other. A total of 1,743 patients received SAVR with an RDV, whereas 14,730 patients were treated with transfemoral TAVR. Patients treated with TAVR were significantly older and had higher surgical risk scores. Following valve replacement, patients treated with an RDV had a significantly higher rate of disabling stroke (1.7% vs. 1.1%; p = 0.03), need for transfusion of >4 red blood cell units (8.5% vs. 1.4%; p < 0.001), and new onset renal replacement therapy (1.9% vs. 1.2%; p = 0.01), whereas the need for a new permanent pacemaker was lower (8.4% vs. 14.9%; p < 0.001). In-hospital mortality was similar (1.6% vs. 1.8%; p = 0.62). These findings persisted after 1:1 propensity score matching, but in-hospital mortality was significantly higher after RDVs (1.7% vs. 0.6%; p = 0.003). Balloon-expandable (BE) RDVs had significantly lower residual gradients compared with BE-THVs, while self-expanding (SE)-RDVs had significantly higher residual gradients compared with SE-THVs. In a large all-comers' registry, TAVR with current-generation THVs was associated with improved in-hospital outcomes compared with SAVR with current-generation RDVs. The pacemaker rate is significantly higher with TAVR. Post-procedural hemodynamic function varied between individual RDVs and THVs.


Concomitant Temozolomide plus radiotherapy for high-grade and recurrent meningioma: a retrospective chart review.
High-grade and recurrent meningiomas are often treatment resistant and pose a therapeutic challenge after surgical and radiation therapy (RT) failure. Temozolomide (TMZ) is a DNA alkylating agent that appears to have a radiosensitizing effect when used in combination with RT and may be worthwhile in meningioma treatment. Thus, we investigated the potential efficacy of concomitant RT plus TMZ compared to historical controls of just RT used in the treatment of high-grade and recurrent meningiomas. We performed a retrospective analysis of patients with meningioma treated at the University of Colorado with TMZ chemoradiation. Progression free survival (PFS) and overall survival (OS) were calculated from the start of chemoradiation to local recurrence or death, respectively. Eleven patients (12 tumors) were treated with chemoradiation with a median follow-up of 41.5 months. There were two WHO grade 1, eight grade 2 and two grade 3 meningiomas. Three patients died during the follow-up period-one being disease related (11.1%). Two patients had meningioma recurrence-at 2.3 months (WHO grade 3), and 5.4 years (WHO grade 2). Three-year OS and PFS for grade 2 meningiomas were each 88%. Historical controls demonstrate a 3-year median OS and PFS of 83% and 75.8%, respectively. Treatment options are limited for meningiomas after local failure. In this study, TMZ chemoradiation demonstrated no significant difference in PFS and OS in the treatment of grade 2 meningiomas compared to historic controls. Further study is warranted to find novel methods for the treatment of malignant and recurrent meningiomas.


Escape from senescence: molecular basis and therapeutic ramifications.
Cellular senescence constitutes a stress response mechanism in reaction to a plethora of stimuli. Senescent cells exhibit cell-cycle arrest and altered function. While cell-cycle withdrawal has been perceived as permanent, recent evidence in cancer research introduced the so-called escape-from-senescence concept. In particular, under certain conditions, senescent cells may resume proliferation, acquiring highly aggressive features. As such, they have been associated with tumour relapse, rendering senescence less effective in inhibiting cancer progression. Thus, conventional cancer treatments, incapable of eliminating senescence, may benefit if revisited to include senolytic agents. To this end, it is anticipated that the assessment of the senescence burden in everyday clinical material by pathologists will play a crucial role in the near future, laying the foundation for more personalised approaches. Here, we provide an overview of the investigations that introduced the escape-from-senescence phenomenon, the identified mechanisms, as well as the major implications for pathology and therapy. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.


Establishing a method of short-term rainfall forecasting based on GNSS-derived PWV and its application.
Global Navigation Satellite System (GNSS) can effectively retrieve precipitable water vapor (PWV) with high precision and high-temporal resolution. GNSS-derived PWV can be used to reflect water vapor variation in the process of strong convection weather. By studying the relationship between time-varying PWV and rainfall, it can be found that PWV contents increase sharply before raining. Therefore, a short-term rainfall forecasting method is proposed based on GNSS-derived PWV. Then the method is validated using hourly GNSS-PWV data from Zhejiang Continuously Operating Reference Station (CORS) network of the period 1 September 2014 to 31 August 2015 and its corresponding hourly rainfall information. The results show that the forecasted correct rate can reach about 80%, while the false alarm rate is about 66%. Compared with results of the previous studies, the correct rate is improved by about 7%, and the false alarm rate is comparable. The method is also applied to other three actual rainfall events of different regions, different durations, and different types. The results show that the method has good applicability and high accuracy, which can be used for rainfall forecasting, and in the future study, it can be assimilated with traditional weather forecasting techniques to improve the forecasted accuracy.


A Gene-for-Gene Relationship Underlying the Species-Specific Parasitism of Avena/Triticum Isolates of Magnaporthe grisea on Wheat Cultivars.
ABSTRACT To elucidate genetic mechanisms of the species-specific parasitism of Magnaporthe grisea, a Triticum isolate (pathogenic on wheat) was crossed with an Avena isolate (pathogenic on oat), and resulting F(1) progeny were subjected to segregation analyses on wheat cvs. Norin 4 and Chinese Spring. We found two fungal loci, Pwt3 and Pwt4, which are involved in the specific parasitism on wheat. Pwt3 operated on both cultivars while Pwt4 operated only on 'Norin 4'. Using the cultivar specificity of Pwt4, its corresponding resistance gene was successfully identified in 'Norin 4' and designated as Rmg1 (Rwt4). The presence of the corresponding resistance gene indicated that Pwt4 is an avirulence locus. Pwt3 was assumed to be an avirulence locus because of its temperature sensitivity. We suggest that gene-for-gene interactions underlie the species-specific parasitism of M. grisea.


[Effect of proliferation-stimulating factors on cholesterol esterification in the serum of rats with acute tetrachloromethane poisoning].
Three phases of cholesterolemia were detected in rats after single administration of CCl4 at a dose of 0.3 ml of oil solution per 100 g of body mass. Factors, stimulating proliferation of hepatocytes and isolated from regenerating liver tissue, did not affect the type of cholesterolemia whereas they stimulated cholesterol esters formation in circulation.


Comparison of Sensitivity and Quantitation between Microbead Dielectrophoresis-Based DNA Detection and Real-Time PCR.
In this study, we describe a microbead-based method using dielectrophoresis (DEP) for the fast detection of DNA amplified by polymerase chain reaction (PCR). This electrical method measures the change in impedance caused by DEP-trapped microbeads to which biotinylated target DNA molecules are chemically attached. Using this method, measurements can be obtained within 20 min. Currently, real-time PCR is among the most sensitive methods available for the detection of target DNA, and is often used in the diagnosis of infectious diseases. We therefore compared the quantitation and sensitivity achieved by our method to those achieved with real-time PCR. We found that the microbead DEP-based method exhibited the same detection limit as real-time PCR, although its quantitative detection range was slightly narrower at 10-10⁵ copies/reaction compared with 10-10⁷ copies/reaction for real-time PCR. Whereas real-time PCR requires expensive and complex instruments, as well as expertise in primer design and experimental principles, our novel method is simple to use, inexpensive, and rapid. This method could potentially detect viral and other DNAs efficiently in combination with conventional PCR.


Clinical, immunologic and genetic profiles of DOCK8-deficient patients in Kuwait.
Deficiency of dedicator of cytokinesis 8 (DOCK8) is a newly described combined primary immunodeficiency disease. It was found to account for 15% of combined immune deficiency cases in the National Primary Immunodeficiency Disorders Registry in Kuwait, a country with high prevalence of consanguinity. We present the clinical, immunologic and molecular characteristics of 9 Kuwaiti patients with DOCK8 deficiency and discuss differences that distinguish DOCK8 deficiency from atopic dermatitis. Clinical immunologists in areas with high incidence of consanguinity should have a high index of suspicion of DOCK8 deficiency in children with recalcitrant eczema, recurrent non-cutaneous infections and lymphopenia.


Clinical potential of pupillary light reflex parameters as objective indicators reflecting chronic rhinosinusitis-specific quality of life: a 12-month prospective longitudinal study.
Pupillary light reflex (PLR) and heart rate variability (HRV) parameters can be objective indicators of chronic rhinosinusitis (CRS) status from the viewpoint of autonomic nervous system activity. This study aimed to establish objective indicators for CRS using the 22-item Sino-Nasal Outcome Test (SNOT-22) and PLR/HRV parameters. Sixty-seven patients were prospectively and longitudinally followed up after surgical treatment. We investigated changes in SNOT-22 scores, representing CRS-specific quality of life (QOL). We prepared two models: linear regression model adjusting clinical factors as predictor variables (model 1) and linear mixed-effects model adjusting clinical factors and among-individual variability (model 2). We compared Akaike's information criterion (AIC) values and regression coefficients. The model with lower AIC values was defined as the better-fit model. Model 2 showed lower AIC values in all parameters (better-fit model). Three parameters showed opposite results between the two models. The better-fit models showed significances in the five PLR parameters but not in any HRV parameters. Among these PLR parameters, constriction latency can be the most robust indicator because of the narrowest 95% confidence intervals. Adjusting the among-individual variability while investigating clinical potential of PLR/HRV parameters to reflect CRS-specific QOL can improve the model fit, thereby reaching robust conclusions from obtained data.


Advances in environmental and occupational disorders in 2014.
In 2014, the Journal published a number of studies that have advanced our understanding of the effects of various environmental factors and immune responses in patients with allergic diseases. In this review we emphasize reports that have appeared in the Journal over the past year that deal with environmental and occupational respiratory disorders and novel approaches to their treatment. The review will focus on the effects of environmental factors and immune responses in allergic airway diseases, identification of new allergens, and risk factors in stinging insect allergy, development of asthma in different age groups, effects of viral infections, and benefits of new therapies.


Thrombomodulin exerts cytoprotective effect on low-dose UVB-irradiated HaCaT cells.
Thrombomodulin (TM) is an endothelial cell surface anticoagulant glycoprotein that performs antimetastatic, angiogenic, adhesive, and anti-inflammatory functions in various tissues. It is also expressed in epidermal keratinocytes. We found that a physiological dose (10mJ/cm(2)) of mid-wavelength ultraviolet irradiation (UVB) significantly induced TM expression via the p38mitogen-activated protein kinase (MAPK)/cyclic AMP response element (CRE) signaling pathway in the epidermal keratinocyte cell line HaCaT; this shows that TM regulates the survival of HaCaT cells. SB203580, a p38MAPK inhibitor, significantly decreased TM expression and the viability of cells exposed to UVB. Furthermore, overexpression of TM markedly increased cell viability, and it was abrogated by TM small interfering RNA (siRNA), suggesting that TM may play an important role in exerting cytoprotective effect on epidermal keratinocytes against low-dose UVB.


Mechanistic aspects regarding the direct aqueous environmental photochemistry of phenol and its simple halogenated derivatives. A review.
We have reviewed the mechanistic aspects regarding the direct aqueous phase environmental photochemistry of phenol and its simple halogenated derivatives. These compounds are important industrial and natural products, are ubiquitous in aquatic systems, and their acute and chronic toxicity makes their environmental fate of interest. Work over the past two decades has unified the photochemistry of phenol and its simple halogenated derivatives. In general, three photochemical pathways dominate in aqueous solution depending on the nature of the substrate: (1) photoionization, (2) photochemical aryl-halogen bond homolysis, and (3) photochemical aryl-halogen bond heterolysis. Photoionization typically results in an array of biaryl radical coupling products which are only relevant for highly concentrated waste streams. Photolytic aryl-halogen bond homolysis will primarily give photoreduction products where reducing agents such as dissolved organic matter or reduced metal cations are present, and radical coupling products in highly concentrated waste streams. The 2- and 4-substituted halophenols may undergo photochemical aryl-halogen bond heterolysis upon irradiation to give an aryl cation. The aryl cation can be attacked by water to give the corresponding hydroxylated derivative, or may deprotonate to generate alpha- and gamma-ketocarbenes, respectively. Following their formation, the singlet alpha-ketocarbenes may undergo Wolff rearrangements to cyclopentadiene-ketenes that are subsequently hydrolyzed to cyclopentadiene carboxylic acids. The triplet alpha- and gamma-ketocarbenes are attacked by oxygen and hydrolyzed to give benzoquinones, directly hydrolyzed to yield hydroquinones, reduced to give phenols, or could take part in coupling reactions in highly concentrated waste streams to give dimers and hydroxybiaryl complexes. Additional studies in natural water samples are required to assess the relative importance of these direct irradiation mechanisms relative to indirect photolysis and other abiotic and biotic degradation and environmental partitioning pathways across the continuum of marine, freshwater, and wastewater biogeochemical signatures.


A new wave of leaders: Early evaluation of the interdisciplinary Foundations of Leadership in Radiation Oncology (FLiRO) program.
Effective leadership across all areas of radiation oncology (RO) is vital to fully realise the benefits of radiation therapy in cancer care. We report outcomes of a novel interdisciplinary leadership program designed for RO professionals under a global joint society initiative. The Foundations of Leadership in RO (FLiRO) program was designed for aspiring RO leaders. Initially delivered in a blended learning format, it was adapted to fully virtual in 2021. It comprised a webinar tutorial, on-line modules and homework followed by 'live' in-person/virtual workshops over an approximately 6-week period. Topics included personal awareness, effective teamwork, quality improvement skills, leading change and conflict management. An immediate post-program online survey was performed using Likert scales to measure self-reported educational value, interaction with others and the likely application of learning to practice. Open comments were invited. 170 participants from 36 countries and 6 continents took part from 2018 to 2021 (99 doctors, 36 physicists, 32 radiation therapists/RTTs and 3 others). 141 (83%) participants responded to the post-program survey. Average weightings for responders' views on whether pre-determined learning objectives were met ranged from 4.30 to 4.61 on a 5-point scale (1 = 'not met at all' and 5 = completely met). For the question addressing potential value of learning for application to their workplace, 124 of 130 (95%) of responders indicated that FLIRO would be 'very useful' or 'extremely useful'. Initial evaluation of the FLiRO program supports its continuation and expansion with ongoing evolution based on emerging evidence around leadership education and participant feedback.


Effects of dietary protein and butylated hydroxytoluene on the kidneys of rats.
Semipurified diet using Na-caseinate or lactalbumin as the only protein source was given to female rats to study the influence of nephrocalcinosis on butylated hydroxytoluene (BHT) induced kidney damage. The study showed, that BHT induces nephropathy in female rats irrespective of the diet used. Pronounced nephrocalcinosis was only found in rats fed the Na-caseinate diet. Thus, this study does not indicate a connection between the development of the BHT-nephropathy and nephrocalcinosis. The results from this study once more stress the influence of the diet on reaction of the animal to experimental procedures.


Denitrification potential of the Northern Arabian Gulf--an experimental study.
The study aims to establish denitrification potential of the Northern Arabian Gulf (NAG), as nitrogen critically affects the ocean productivity, obliterates acidity, oxidative capacity and radiative transfer capability of atmosphere. The experimental study was conducted by taking cores from intertidal zones from two different sites in North and South, referred as sites N and S; representing two distinct environmental milieu. The experiment was conducted in controlled laboratory conditions simulating the tidal cycles. Multiple cores were taken and loaded with seawater with different N concentrations, the redox potential was established for each condition. Redox potential was significantly lower at 10 cm depth compared to the surface in all cores (P < 0.001). The redox potential at surface and at 10 cm depth was significantly lower at site S compared to site N (P < 0.001; F = 714.2), suggesting anaerobic sediments at site S. Effects of nitrate spiked seawater on denitrification under nonflooded and flooded conditions at the two sites were also studied. Three-way ANOVA analysis indicated that site, nitrate concentration, and flooding had significant main and interactive effects on the rate of denitrification. The results suggest that under ambient nitrate concentrations (0.03 mg NO(3)-N l(-1)), 6.3 ± 2.1 g NO(3)-N ha day can be denitrified by inter-tidal zone sediments. At a nitrate concentration of 1 mg NO(3)-N l(-1), 92 ± 16 g NO(3)-N ha day may be denitrified whilst at a very high nitrate load of 10 mg NO(3)-N l(-1), the sediments may attain a rate of denitrification close to 404 ± 78 g NO(3)-N ha day.


The kinetic characterization and X-ray structure of a putative benzoylformate decarboxylase from M. smegmatis highlights the difficulties in the functional annotation of ThDP-dependent enzymes.
Benzoylformate decarboxylase (BFDC) is a thiamin diphosphate (ThDP)-dependent enzyme that catalyzes the nonoxidative decarboxylation of benzoylformate. It is the penultimate enzyme in both the mandelate pathway and the d-phenylglycine degradation pathway. The ThDP-dependent Enzyme Engineering Database (TEED) now lists more than 800 sequences annotated as BFDCs, including one from Mycobacterium smegmatis (MsBFDC). However, there is no evidence that either pathway for benzoylformate formation exists in the M. smegmatis genome. Further, sequence alignments of MsBFDC with the well characterized enzyme isolated from Pseudomonas putida (PpBFDC) indicate that there will be active site substitutions in MsBFDC likely to reduce activity with benzoylformate. Taken together these data would suggest that the annotation is unlikely to be correct. To test this hypothesis the putative MsBFDC was cloned, expressed, purified, and the X-ray structure was solved to a resolution of 2.2Å. While showing no evidence for ThDP in the active site, the structure was very similar to that of PpBFDC. A number of 2-oxo acids were tested as substrates. For MsBFDC the K(m) value for benzoylformate was ~23 mM, nearly 100-fold greater than that of PpBFDC while the k(cat) value was reduced 60-fold. These values would suggest that benzoylformate is not the physiological substrate for this enzyme, and that annotation as a 2-oxo acid decarboxylase may be more appropriate.


Physical separation and functional interaction of Kluyveromyces lactis and Saccharomyces cerevisiae ARS elements derived from killer plasmid DNA.
Two DNA fragments which have autonomously replicating sequence (ARS) activity in both Saccharomyces cerevisiae and Kluyveromyces lactis have been isolated from the K. lactis kl killer plasmid. One fragment (Kla1) is 700 base pairs (bp) in length and plasmids carrying it are mitotically unstable in both hosts. In K. lactis, this instability leads to colonies having a 'nibbled' phenotype when grown on selective media and appears to be the result of inefficient plasmid segregation. The other fragment (Kla2) is an artificial junction fragment of 1100 bp which was produced during the cloning procedure. Kla2 has been divided into two sub-fragments Kla2A and Kla2B which have, respectively, ARS activity in K. lactis and S. cerevisiae but not the other species. This indicates that these two closely related yeasts have different sequence requirements for ARS activity. Kla2B contains a perfect match to the S. cerevisiae ARS consensus but Kla2A does not. Both Kla2A and Kla1 share a 10 bp sequence as the sole region of homology between them. This sequence, 5'TCATAATATA3', is tentatively offered as defining the ARS consensus sequence for K. lactis.


Is it worth to insert uterine pack instead of Bakri balloon to control postpartum hemorrhage after vaginal delivery in hypertensive patients?
To assess the safety and effectiveness of uterine packing with gauze compared to Bakri balloon to control postpartum hemorrhage (PPH) after vaginal delivery in patients with hypertensive disorders with pregnancy (HDP). This was a prospective observational study conducted on 142 patients with HDP who suffered atonic PPH following vaginal delivery and were allocated either to insert uterine packing with gauze (n = 68) or insertion of Bakri balloon (n = 74). Success of the tamponade to arrest bleeding was the primary outcome measure. Data was collected and analyzed. Most of the included patients experienced spontaneous onset of labour (69%), had not receive I.V. antihypertensive drugs (83.1%) or magnesium sulphate (94.4%), or calcium channel blocker (95.7%), underwent spontaneous vaginal delivery (85.9%), received Pethidine by IMI for pain relief during labour (67.6%), did not need an episiotomy (59.2%), with spontaneous delivery of the placenta (95.77%). Bakri balloon was associated with a shorter duration to insert (p < 0.001), a higher failure rate with the need for laparotomy (p < 0.05) and more post-delivery hospital stay compared to uterine packing (p < 0.001). Although uterine packing with gauze to control PPH after vaginal delivery in patients with HDP requires a longer time to insert compared to Bakri balloon yet associated with a lesser need for laparotomy and shorter hospital stay. Larger trials are warranted to confirm or refute these findings.


Symptomatic corpus spongiosum defect in adolescents and young adults who underwent distal hypospadias repair during childhood.
Several popular surgical techniques have been described for the repair of distal hypospadias; however, the role of repairing the corpus spongiosum was rarely discussed. Herein we review our experience with adolescents who underwent hypospadias repair during childhood. Their main complaints were partially or totally related to spongiosum deficiency, the surgical outcomes are also discussed. Between 2007 and 2018, 25 patients aged between 13 and 28 years of age (median 19 years) were operated upon to repair the deficiency or absence of corpus spongiosum in addition to a Thiersch-Duplay urethroplasty. Their records indicated that the primary hypospadias repairs during childhood included MAGPI (N = 10) and TIPU (N = 9), in 6 patients the repair of the distal hypospadias was unknown. The main complaints were; abnormal urinary stream which patients described as spraying and/or dripping of urine (N = 10) and distal urethral swelling during voiding and dripping of urine post voiding (N = 15). Eight patients reported that they were treated for symptomatic recurrent urinary tract infections by their primary physicians. In 5 patients, the urethral wall was thin and covered with adherent epidermis only. In 20 patients, the laterally displaced spongiosum pillars were well-defined, 4 of whom exhibited mild chordee. In 14 patients the spongiosum pillars were mobilized and approximated using interrupted absorbable sutures. Four patients had spongiosum deficiency and urethral swelling resulting in mild diverticulum formation. The urethral wall was plicated and covered with the spongiosum and/or dartos flaps. In 4 patients the spongiosum pillars were fixed and could not be mobilized to provide a tension-free closure. In these cases, a dartos flap harvested from the scrotum, and used to cover the urethral wall and was sutured on either side to the spongiosum pillars. 12/25 patients underwent glandular contouring and/or meatoplasty simultaneously to improve the penile esthetics. The follow-up period varied between 18 months and 7 years (mean 3.5 years). 24/25 patients reported a normal steady urinary stream, absence of urethral swelling during voiding and none (22) or minimal (2) postvoid droplets of urine which soiled the underwear. One patient developed glans dehiscence and is voiding through a coronal meatus; he declined further surgery. None developed symptomatic urinary infection. The spongioplasty corrected the mild curvature in all 4 patients. Failure to recognize and/or correct the deficient corpus spongiosum during the repair of distal hypospadias during childhood may become symptomatic during adolescence however, the abnormality can be corrected successfully.


Effects of transient temperature increases on odor production from thermophilic anaerobic digestion.
The City of Los Angeles, Bureau of Sanitation, has implemented thermophilic anaerobic sludge digestion at the Hyperion and Terminal Island Treatment Plants (HTP and TITP). A two-stage continuous-batch process was established at HTP, while a single-stage sequencing batch process was established at TITP. This was to evaluate compliance with the Class A pathogen reduction requirements of U.S. EPA 40 CFR Part 503. A rapid increase of the digester temperature at TITP from 57.5 to 65.5 degrees C caused an increase of the volatile fatty acid to alkalinity ratio, a decline in digester performance, and an elevated production of methyl mercaptan and hydrogen sulfide. A rapid increase of the digester temperature at HTP from 54 to 58 degrees C caused an elevated production of methyl mercaptan, but the effect on the volatile fatty acid to alkalinity ratio and digester performance was insignificant. It is likely that these effects observed at TITP and HTP were transient responses to rapid changes in temperature.


Clomipramine and EEG sleep in depression.
Recent studies with clomipramine (CMI) have demonstrated that a pulse-loading approach is associated with a rapid improvement in symptomatology in the absence of continuous treatment. In the present study, sleep changes were evaluated to ascertain the rapidity of clomipramine's effect on electroencephalographic sleep, especially rapid eye movement (REM) and delta wave sleep measures. Clomipramine produced rapid changes in sleep with reduced sleep continuity and almost complete suppression of REM sleep as well as a redistribution of slow wave sleep. Delta waves during sleep were also found to be shifted to the earlier part of the night and increased in intensity. Spectral analysis revealed an increase in power in the delta frequency range that was correlated with clinical responsiveness. These studies point toward a role for clomipramine in the rapid treatment of depression and confirm that sleep physiology may be a good predictor of antidepressant action.


Diallyl trisulfide reduced the reproductive capacity of male Sitotroga cerealella via the regulation of juvenile and ecdysone hormones.
Environmental pollution and resistance in animals are major concerns for the application of synthetic pesticides. Diallyl trisulfide (DAT), an active compound in garlic essential oil, is a novel tool for active and safe control of agricultural insect pests. In this study, we analysed the effects of DAT (0.01 μL/L) on the protein content in male reproductive tissues (accessory glands, ejaculatory ducts, and testis), and juvenile hormone (JH) and ecdysone titres in a highly detrimental pest of stored products, Sitotroga cerealella. Evaluation of the expression profile of JH and ecdysone pathway-related genes in various tissues indicated that the accessory gland protein and ecdysone titres were markedly decreased after DAT fumigation, whereas the testis protein content and JH titre were increased. However, the protein content of the ejaculatory ducts remained unchanged between the treated and control groups. Further investigation revealed that DAT disrupted the mRNA expression of key enzymes involved in JH and ecdysone pathways. While increased mRNA levels of juvenile hormone acid O-methyltransferase (JHMAT) and Kruppel homologue 1 (Kr-h1) were observed after 4 and 7 h of DAT fumigation, the levels of juvenile hormone epoxide hydrolase (JHEH) were substantially reduced 3 h post-fumigation. mRNA levels of the ecdysone-responsive gene, FTZF1, and cytochrome P450 enzyme, CYP315A1, were notably decreased at 7 h and 4 h, respectively, post-fumigation, whereas CYP314A1 and CYP302A1 mRNA levels decreased after 3 h and 4 h, respectively. While DAT fumigation disrupted sperm number in the testis, ejaculatory ducts, and seminal vesicles, topical application of the 20-hydroxyecdysone (20E) analogue also lowered sperm number in the ejaculatory ducts. Topical application of methoprene, a JH analogue, increased the protein content in the testes, but not in the accessory glands or ejaculatory ducts. However, the survival rate was not affected by the topical application of methoprene or 20E. These data suggest that DAT regulates JH and ecdysone via its molecular pathway genes and modulates endocrine secretion during the male reproductive process.


Incidental encounter of intraperitoneal tuberculosis during renal surgeries: A surgeon's dilemma.
Tuberculosis is a major healthcare burden in India, which accounts for the maximum number of cases worldwide. Due to its non-specific features, peritoneal tuberculosis has been dubbed as the great mimicker of various other abdominal pathologies. This case series highlights the importance of incidental intra operative detection of peritoneal tuberculosis in cases being operated for renal pathologies. Diagnostic and therapeutic dilemma is bound to occur when surgeon is faced with such an unexpected finding. Incidental peritoneal tuberculosis was defined as peritoneal tubercular lesions (ascites or tubercles) detected intraoperatively in patients being operated for non-tuberculosis related indications and no prior preoperative suspicion of abdominal tuberculosis. We here review 3 cases with different renal pathologies and no prior history or exposure to tuberculosis in which intraperitoneal tuberculosis was encountered incidentally at the time of surgery. Case 1 was a suspected case of right renal cell carcinoma and underwent right robotic nephron sparing surgery. Case 2 underwent robotic assisted lap simple nephrectomy for a right nonfunctioning kidney due to obstructive ureteric calculus. Case 3 was a suspected case of left upper tract urothelial carcinoma who underwent robotic nephroureterectomy with bladder cuff excision. In all 3 cases, on encountering the peritoneal lesions, an intraoperative decision to continue with the proposed surgery was made after frozen section biopsies from the multiple peritoneal and omental deposits revealed no malignant cells. Histopathology of these lesions in all 3 cases revealed caseating granulomas consistent with a diagnosis of disseminated peritoneal tuberculosis. None of the resected specimen had features suggestive of tuberculosis. ATT was started and on follow up the patients are doing well. Peritoneal tuberculosis although uncommon is not a rare presentation of active tuberculosis. Surgeons on encountering such lesions during non-related surgeries should always have a high suspicion of tuberculosis. Despite the existing literature favoring abandoning the procedure in such situations, we successfully completed the proposed surgeries.


Prevalence of gambling among Minnesota public school students in 1992 and 1995.
The purposes of this study were to examine the prevalence of gambling among youth, compare rates of gambling between 1992 and 1995, and determine what levels of gambling frequency may be considered common and uncommon. The two samples included 122,700 Minnesota public school students in the 6th, 9th, and 12th grades in 1992; and 75,900 9th and 12th grade students in 1995. Students were administered the Minnesota Student Survey, a 126-item, anonymous, self-administered, paper-and-pencil questionnaire that inquires about multiple content domains, including gambling behaviors. The same questionnaire, with minor revisions to the gambling items, was administered in both 1992 and 1995 to students in their classrooms by the Minnesota Department of Education. There were slight decreases in overall gambling rates from 1992 to 1995. The majority of students gambled at least once during the past year. However, most did not play any game on a weekly/daily rate and did not report any problems associated with their gambling. Gender, grade, and race effects were found for gambling frequency. Boys gambled more often than girls, and 9th and 12th grade students gambled more often than 6th grade students. Asian American and White students reported lower rates of gambling frequency than Mexican/Latin American, African American, and American Indian students. From a statistical standpoint (i.e., beyond the 97.7 percentile), it may be considered in the uncommon range for girls to play two or more games at a weekly/daily rate, and for boys to play four or more games at a weekly/daily rate. Variables associated with gambling frequency included antisocial behavior, gender, and alcohol use frequency. Although the finding that gambling did not increase from 1992 to 1995 is encouraging, this is the first generation of youth to be exposed to widespread accessibility to gambling venues and gambling advertising and it will be important to continue monitoring the prevalence of youth gambling.


Chronic Pruritus and Connective Tissue Disorders: Review, Gaps, and Future Directions.
Chronic itch is a common skin manifestation in many connective tissue diseases. However, the cause of chronic itch in these diseases is still not fully understood. The complex, and in some cases incomplete understanding of, pathogenesis in each condition makes it difficult to target specific mediators of chronic itch. It is important to better understand the pathophysiology of chronic itch in these conditions, as this information might provide a fuller understanding of the pathogenesis of the diseases in general and lead to the development of more specific treatments for connective tissue diseases in patients with chronic itch. We present a review of the literature on what is known about the prevalence, possible pathophysiology, and effect on quality of life of chronic itch in patients with scleroderma, Sjögren's syndrome, dermatomyositis, systemic lupus erythematosus, cutaneous lupus erythematosus, and mixed connective tissue disease.


Cytotoxicity evaluation of Curcuma zedoaria (Christm.) Roscoe fluid extract used in oral hygiene products.
This in vitro study evaluated the cytotoxic effects of the Curcuma zedoaria (Christm.) Roscoe (popular name: zedoary) fluid extract, as used in preparations for oral hygiene, mostly for anti-septic purposes. The cell viability and cell growth were assessed by Trypan blue dye exclusion assay using the LMF cell line derived from oral mucosa. Cell viability (short-term assay) was measured 0, 6, 12 and 24 h after contact with the fluid extract. Cell growth (long-term assay) was analyzed in 1, 3, 5 and 7 days. The experimental groups were those testing the fluid extract obtained from the zedoary rhizome and the extractor liquid (ethanol 70° GL) in the concentrations of 0.01-0.0001% v/v. Fresh DMEM were used in the control cultures. Short-term assay-all studied cultures maintained stable cell viability; Long-term assay-there was progressive cell growth in all studied cultures. According to the results, the zedoary fluid extract presents low cytotoxicity and probably can be used in the oral hygiene products.


Electrophoretic methods for process monitoring and the quality assessment of recombinant glycoproteins.
In many ways electrophoretic techniques appear ideal for quality monitoring of proteins and are thus well suited for the analysis of recombinant glycoproteins. The requirements of high throughput, comparative analysis and resolution of many variants are met by several electrophoretic techniques. A wide variety of such techniques are available to biotechnologists in the rapidly developing area of recombinant glycoproteins. It is the aim of this review to specifically cover recent work which has been applied to the analysis of DNA-derived glycoproteins, both from a process control standpoint and final product validation. All major areas of electrophoresis including sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), isoelectric focusing and techniques utilizing capillary electrophoresis are covered, with emphasis on analysis of glycoforms and oligosaccharide profiles of recombinant glycoproteins. As illustration, actual examples rather than standard glycoproteins are given to indicate the potential and limitations which may be encountered. It is anticipated that this review will prove a useful and practical guide to the latest developments by indicating the relevant merits of different methods.


Chicken fumarase. II. Kinetic studies.
The catalysis of the hydration of fumarate and deshydration of L - malate by chicken fumarase was measured spectrophotometrically over a range of substrate concentrations from 4 times 10(-3) M to 8 times 10(-5) M for fumarate and from 8 times 10(-2) M to 10(-3) M for L - malate. For the forward and reverse reactions, linear Lineweaver and Burk plots were obtained. The Michaelis constants and the maximum initial velocities for both substrates were determined and the Haldane relation was found to be obeyed. The effect of pH on activity was investigated over a pH range from 5.5 to 9.0 and the data indicate the presence, in the active site, of two ionizable groups, one in the acidic form and one in the basic form. The values of the ionization constants, determined for the enzyme - substrate complexes, agree closely with the ones obtained for the porcine enzyme. The mode of action of twenty-four structural analogs on the initial velocity of the dehydration of L-malate, by chicken fumarase was examined. From these studies, two regions positively charged appear necessary for the effective binding of the carboxylates of the substrates and competitive inhibitors to the active center. Moreover, the data suggest the presence of an additional group, in the catalytic site of chicken fumarase, that stabilizes the carbon-carbon double bond common to fumarate and its structural analogs. Finally, from the comparison of the kinetic properties of the chicken and pig fumarases, it may be concluded that the catalytic mechanism of the homologous enzymes are very similar, if not identical.


Enhanced tryptophan catabolism in the absence of the molecular adapter DAP12.
DAP12 is an immunoreceptor tyrosine-based activation motif-bearing membrane adapter molecule expressed by different cell types. Although several receptors associate with DAP12 in murine dendritic cells (DC), the function of these receptors is as yet unknown. Here we report that splenic mature DC with DAP12 overexpression are characterized by an impaired tolerogenic potential. In contrast, inhibition of DAP12 function results in enhanced tolerogenesis and constitutive expression of immunosuppressive tryptophan catabolism mediated by indoleamine 2,3-dioxygenase (IDO). Increased resistance to experimental encephalomyelitis is observed in DAP12 knockin mice, which is dependent on IDO expression. Therefore, DAP12-related receptors act as negative regulators of IDO-mediated tolerance in vivo.


Influence of maternal education on child immunization and stunting in Kenya.
In 2003, the child mortality rate in Kenya was 115/1000 children compared to 88/1000 average for Sub-Saharan African countries. This study sought to determine the effect of maternal education on immunization (n=2,169) and nutritional status (n=5,949) on child's health. Cross-sectional data, Kenya Demographic Health Survey (KDHS)-2003 were used for data analyses. 80% of children were stunted and 49% were immunized. After controlling for confounding, overall, children born to mothers with only a primary education were 2.17 times more likely to be fully immunized compared to those whose mothers lacked any formal education, P<0.001. For nutrition, unadjusted results, children born to mothers with primary education were at 94% lower odds of having stunted growth compared to mothers with no primary education, P<0.01. Policy implications for child health in Kenya should focus on increasing health knowledge among women for better child health outcomes.


Successful Treatment of Severe COVID-19 Pneumonia With Clazakizumab in a Heart Transplant Recipient: A Case Report.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is characterized by an overwhelming cytokine response. Various treatment strategies have been attempted. A 61-year-old man with heart transplantation in 2017 presented with fever, cough, and dyspnea, and was confirmed positive for coronavirus disease 2019 (COVID-19). Laboratory tests showed significant elevations in C-reactive protein and interleukin-6 (IL-6). Echocardiogram showed left ventricular ejection fraction 58% (with ejection fraction 57% 6 months prior). Given the lack of clear management guidelines, the patient was initially managed symptomatically. However, the patient subsequently had a rapid respiratory deterioration with worsening inflammatory markers on day 5 of admission. Tocilizumab (anti-IL-6R) was in low supply in the hospital. The patient was offered clazakizumab (anti-IL-6) for compassionate use. Patient received 25 mg intravenously × 1 dose. Within 24 hours, he showed significant improvement in symptoms, oxygen requirements, radiological findings, and inflammatory markers. There was a transient leukopenia that improved in 4 days. He was discharged home on day 11, with negative nasopharyngeal SARS-CoV-2 PCR as an outpatient on day 35, development of positive serum COVID-19 IgG antibody, and he continued to do well on day 60, with no heart-related symptoms. Clazakizumab is a monoclonal antibody against human IL-6, which may be helpful in inhibiting the cytokine response to SARS-CoV-2 in COVID-19. Although not yet FDA approved, it is being investigated for treatment of renal antibody-mediated rejection. Clinical trials of clazakizumab for treatment of COVID-19 are underway worldwide.


Impaired energy metabolism and abnormal muscle histology in mut- methylmalonic aciduria.
The authors report a 27-year-old man with B12-responsive mut- methylmalonic aciduria associated with pure muscle symptoms. Two mutations were found in the methylmalonyl-CoA mutase gene. An exercise test showed a reduced maximal workload and reduced oxygen uptake, and a muscle biopsy showed subsarcolemmal accumulation of mitochondria and normal respiratory chain enzyme activities. These findings may be caused by inhibition of mitochondrial energy metabolism by methylmalonate or its metabolites.


Iron status in patients receiving erythropoietin for dialysis-associated anemia.
Adequate body iron stores are crucial to assuring rapid and complete response to recombinant human erythropoietin (rHuEPO). In the present study, markers of iron storage were examined in 27 patients with normochromic, normocytic anemia undergoing acute rHuEPO (150 to 300 U/kg t.i.w.) treatment for anemia. We calculated projected iron needed for new hemoglobin synthesis from the difference between initial and target hemoglobin concentrations, initial iron reserves available from initial serum ferritin levels, and net projected surplus or deficit from the difference between needs and reserves. Of 22 patients predicted to develop iron deficiency (mean projected deficit 268 +/- 70 mg), 20 developed evidence of exhausted iron stores (transferrin %sat less than 16 or ferritin less than 30 micrograms/liter) before reaching target hemoglobin; two predicted to become deficient (projected deficit less than 100 mg) did not; and all five predicted to avoid iron deficiency (mean projected surplus 177 +/- 20 mg) remained iron replete. During acute rHuEPO therapy net body iron balance remained neutral in patients receiving no iron supplements and increased 5 mg/kg in patients prescribed oral ferrous sulfate. However, in patients given iron dextran i.v. less than 60% of elemental iron administered became measurable as iron stores or usable for hemoglobin synthesis.


Calpain 10 gene and laryngeal cancer: a survival analysis.
Laryngeal carcinoma is a common upper respiratory tract cancer with different environmental and genetic factors involved in its development. Calpains are Ca2+-dependent cysteine proteases that modulate cellular function. A novel association between calpain 10 (CAPN10) haplotypes and laryngeal cancer has been found recently. Therefore, the goal of this study was to analyze the contribution of CAPN10 alleles to laryngeal cancer survival. Patients were recruited from southern Spain. Genotypes were determined using pyrosequencing technology. We analyzed CAPN10 UCSNP-44, UCSNP-43, UCSNP-19, and UCSNP-63 allelic distributions in 199 patients with unrelated laryngeal cancer. Survival curves were calculated from the date of the intervention to the date of death. Multivariate analyses were done using the Cox proportional risk model. UCSNP-19, UCSNP-43, and UCSNP-44 were unrelated to survival in both univariate and multivariate analyses. However, for UCSNP-63 genotype 12 a significant relationship was observed in multivariate analysis (hazard ratio [HR] = 2.73; 95% confidence interval [CI], 1.21-6.20). CAPN10 UCSNP-63 genotype 12 seems to be related with a worse prognosis in laryngeal cancer.


Evolution of testing strategies for genetic toxicity.
Shortly following the inception of genetic toxicology as a distinct discipline within toxicology, questions arose regarding the type and number of tests needed to classify a chemical as a mutagenic hazard or as a potential carcinogen. To some degree the discipline separated into two sub-specialties, (1) genetic risk assessment and (2) cancer prediction since data from experimental oncology also supports the existence of a genotoxic step in tumor initiation. The issue of which and how many tests continued to be debated, but is now focused more tightly around two independent phenomena. Tier or sequential testing was initially proposed as a logical and cost-effective method, but was discarded on the basis that the lower tier tests appeared to have too many false responses to force or exclude further testing of the test agent. Matrix (battery) testing was proposed for screening on the hypothesis that combinations of endpoints and multiple phylogenetic target organisms were needed to achieve satisfactory predictability. As the results from short-term test 'validation' studies for carcinogen prediction and evaluations of EPA's Gene-Tox data accumulated, it became obvious that qualitative differences remained between predictive and definitive tests and by assembling different combinations of short-term assays investigators did not appear to resolve the lack of concordance. Recent trends in genetic toxicology testing have focused on mathematical models for test selection, and standardized systems for multi-test data assessment.


Factors influencing inadequate and excessive weight gain in pregnancy: Colorado, 2000-2002.
To identify the biological, psychosocial, and behavioral characteristics that are associated with inadequate and/or excessive weight gain in pregnancy. Univariate, bivariate, and multiple logistic regression analyses were conducted using data from Colorado's 2000-2002 Pregnancy Risk Assessment Monitoring System (PRAMS). Independent variables included biological risk factors (prepregnancy BMI, parity, preterm labor, maternal morbidity), psychosocial risk factors (pregnancy intention, WIC and Medicaid enrollment, area of residence, age, race/ethnicity, education, and stressors), and behavioral risk factors (smoking and drinking alcohol in the last trimester of pregnancy). In the bivariate analysis, all the biological risk factors were significantly associated with the pregnancy weight gain distribution, as were several of the psychosocial risk factors (WIC and Medicaid enrollment, area of residence, race/ethnicity, and maternal education). Smoking and alcohol use were not significant. After controlling for other variables through logistic regression, the only characteristics associated with inadequate weight gain were parity, underweight or obesity, preterm labor, nausea, residence in a rural area, low levels of education, and smoking. The characteristics associated with excessive weight gain were overweight or obesity, high blood pressure, and having 12 years of education. Having a pre-pregnancy BMI above 29 greatly increases the risk for both inadequate and excessive weight gain. Unfortunately, obesity, like the other major risk factors identified here (maternal education and parity) are not modifiable after a given pregnancy begins. To address these problems, a sustained approach to women's health, education, and well-being across the lifespan will be required, rather than a reliance upon targeted interventions during pregnancy.


Closed rupture of flexor tendon by hyperextension mechanism in wrist level (zone V): a report of three cases.
Closed flexor tendon ruptures due to trauma without external wound are rare. When the flexor tendon has excessive loading, failure occurs at the tendon insertion or its origin from the bone. It is likely to result in avulsion fracture rather than rupture of the proper portion of the tendon by forceful grasping with hyperextension. However, we have experienced three cases of closed flexor tendon ruptures at zone V, caused by forceful grasping or hyperextension mechanism against resistance. On physical examination, these patients could not flex interphalangeal joint of thumb or distal interphalangeal joint of the fifth finger. All patients underwent MRI or ultrasonography to find out the location of loss in continuity of the flexor tendons before the operation. After identifying the location, flexor tendon repair or tendon graft using palmaris longus were performed.


Changes in Morphology, Metabolism and Composition of Cuticular Wax in Zucchini Fruit During Postharvest Cold Storage.
Cuticle composition is an important economic trait in agriculture, as it is the first protective barrier of the plant against environmental conditions. The main goal of this work was to study the role of the cuticular wax in maintaining the postharvest quality of zucchini fruit, by comparing two commercial varieties with contrasting behavior against low temperatures; the cold-tolerant variety 'Natura', and the cold-sensitive 'Sinatra', as well as 'Sinatra' fruit with induced-chilling tolerance through a preconditioning treatment (15°C for 48 h). The freshly-harvested 'Natura' fruit had a well-detectable cuticle with a significant lower permeability and a subset of 15 up-regulated cuticle-related genes. SEM showed that zucchini epicuticular waxes mainly consisted of round-shaped crystals and clusters of them, and areas with more dense crystal deposition were found in fruit of 'Natura' and of preconditioned 'Sinatra'. The cuticular wax load per surface was higher in 'Natura' than in 'Sinatra' fruit at harvest and after 14 days at 4°C. In addition, total cuticular wax load only increased in 'Natura' and preconditioned 'Sinatra' fruit with cold storage. With respect to the chemical composition of the waxes, the most abundant components were alkanes, in both 'Natura' and 'Sinatra', with similar values at harvest. The total alkane content only increased in 'Natura' fruit and in the preconditioned 'Sinatra' fruit after cold storage, whereas the amount of total acids decreased, with the lowest values observed in the fruit that showed less chilling injury (CI) and weight loss. Two esters were detected, and their content also decreased with the storage in both varieties, with a greater reduction observed in the cold-tolerant variety in response to low temperature. Gene expression analysis showed significant differences between varieties, especially in CpCER1-like and CpCER3-like genes, involved in alkane production, as well as in the transcription factors CpWIN1-like and CpFUL1-like, associated with cuticle development and epidermal wax accumulation in other species. These results suggest an important role of the alkane biosynthetic pathway and cuticle morphology in maintaining the postharvest quality of zucchini fruit during the storage at low temperatures.


Dopamine modifies the balance of rod and cone inputs to horizontal cells of the Xenopus retina.
Dopamine (greater than or equal to 2 microM) increased the cone input and suppressed the rod input to axon-bearing horizontal cells of the Xenopus retina. Dopamine (10 microM) also depolarized the horizontal cell by about 9 mV. The D2-dopamine antagonists spiperone and metoclopramide had the opposite action to dopamine, whereas the D1-dopamine antagonist SCH 23390 was without effect. None of the agents tested modified the light-evoked responses of rods.


[Anatomy, variations and malformations of the vessels of the head and neck region (author's transl)].
After a short review of developmental data concerning the head and neck arteries, the normal conditions, variations and malformations of single arteries are described. Special attention is paied to the skeletotopic and topographic relations of the arteries. In every bigger vessel its length, position, origin and branches are described, and in most cases are also demonstrated by diagrams and tables. As the aortic arch may also reach the neck region, its variation and malformations as well as the variations of its branches are mentioned. The variations and the malformations of the inominate artery, of the common carotid artery, as well as of the external and internal carotid arteries are described. The practical importance of these variations is stressed. Upon description of variations and malformations anatomical, surgical und roentgenological findings described in literature, as well as personal experiences are considered. Special attention has been paied to the variations of the circulus arteriosus Willisi, to the persistence of the presegmental arteries and to the possibility of formation of a by-pass in occlusion or aplasia of cerebral arteries. The position of the subclavian artery, its variations and the variations of its branches are described. After a short embryological introduction, the variations of the venous system and its anastomoses are described. At the end, the main variations of the big lymphatic vessels in the neck are mentioned.


Estimation of the Level of Abasic Sites in Plant mRNA Using Aldehyde Reactive Probe.
Oxidation of RNA is associated with the development of numerous disorders including Alzheimer's and Parkinson's diseases, amyotrophic lateral sclerosis (ALS), cancer, and diabetes. Additionally, a correlation has been found between increase in RNA oxidation and the process of aging. In plants, elevated level of oxidatively modified transcripts has been detected during alleviation of seeds dormancy and stress response. Increasing interest on the topic of RNA oxidative modifications requires elaboration of new laboratory techniques. So far, the most common method used for the assessment of RNA oxidation is quantification of 8-hydroxyguanine (8-OHG). However, reactive oxygen species (ROS) induce also numerous other changes in nucleic acids, including formation of abasic sites (AP-sites). Recently, the level of AP-sites in RNA has been measured with the use Aldehyde Reactive Probe (ARP). In the present chapter, we describe application of this technique for the evaluation of the level of AP-sites in plant transcripts.


Ultrasound imaging versus morphopathology in cardiovascular diseases. Myocardial cell damage.
This review article summarizes the results of histopathological and clinical imaging studies to assess myocardial necrosis in humans. Different histopathological features of myocardial cell necrosis are reviewed. In addition, the present role of echocardiographic techniques in assessing irreversible myocardial damage is briefly summarized.


Multi-targeted prevention and therapy of cancer by proanthocyanidins.
In recent years, a considerable emphasis has been focused on the importance of the naturally available botanicals that can be consumed in an individual's everyday diet and that can also be useful as a chemopreventive or chemotherapeutic agent for certain diseases, including cancers. A wide variety of botanicals, mostly dietary flavonoids or polyphenolic substances, have been reported to possess substantial anti-carcinogenic and antimutagenic activities because of their antioxidant and anti-inflammatory properties. Proanthocyanidins are considered as one of them, and are abundantly available in various parts of the plants, such as fruits, berries, bark and seeds. Their modes of action were evaluated through a number of in vitro and in vivo studies which showed their potential role as anti-carcinogenic agent. We summarize and highlight the latest developments on anti-carcinogenic activities of proanthocyanidins from different sources, specifically from grape seeds, and their molecular targets, such as NF-kappaB, mitogen-activated protein kinases, PI3K/Akt, caspases, cytokines, angiogenesis and cell cycle regulatory proteins and other check points, etc. Although the bioavailability and metabolism data on proanthocyanidins is still largely unavailable, certain reports indicate that at least monomers and smaller oligomeric procyanidins are absorbed in the gut. The modulation of various molecular targets by proanthocyanidins in vitro and in vivo tumor models suggests their importance, contribution and mechanism of action to the prevention of cancers of different organs.


Corrigendum: Potential genetic overlap between insomnia and sleep symptoms in major depressive disorder: A polygenic risk score analysis.
[This corrects the article DOI: 10.3389/fpsyt.2021.734077.].


Bacteremia and Deep Vein Thrombosis in an Infant.
Deep vein thrombosis (DVT) is rare in infancy. In pediatric populations, thrombosis occurs most frequently in hospitalized children and those with central venous catheters. The presence of a DVT in the general pediatric population indicates a hypercoagulable state and requires rapid diagnosis and treatment of both the thrombosis and the underlying process. A previously healthy 6-month-old male was brought to the emergency department by his family with a chief complaint of left leg swelling. Duplex ultrasonography in the emergency department revealed multiple DVTs in the leg vasculature. The patient was treated with anticoagulation and antibiotic therapy in the emergency department and admitted. Blood cultures revealed the subsequent growth of methicillin-resistant Staphylococcus aureus (MRSA). WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: While rare in infants, new-onset swelling in an extremity may be caused by thrombosis and be the initial symptom of an underlying hypercoagulable state. Duplex ultrasonography is a relatively benign test that can be readily performed in most emergency departments, and it allows physicians to rule out thrombosis. When present, DVT in the general pediatric population can indicate a critical illness, such as malignancy or infection, and requires rapid treatment and admission to a pediatric service for management.


Development of a Streptomyces-based system for facile thioholgamide library generation and analysis.
Derivatizing natural products (NPs) is essential in structure-activity relationship (SAR) studies, compound optimization, and drug development. Ribosomally synthesized and post-translationally modified peptides (RiPPs) represent one of the major classes of natural products. Thioholgamide represents thioamitide - a recently emerged family of RiPPs with unique structures and great potential in anticancer drug development. Although the method for generating the RiPP library by codon substitutions in the precursor peptide gene is straightforward, the techniques to perform RiPP derivatization in Actinobacteria remain limited and time-consuming. Here, we report a facile system for producing a library of randomized thioholgamide derivatives utilizing an optimized Streptomyces host. This technique enabled us to access all possible amino acid substitutions of the thioholgamide molecule, one position at a time. Out of 152 potential derivatives, 85 were successfully detected, revealing the impact of amino acid substitutions on thioholgamide post-translational modifications (PTMs). Moreover, new PTMs were observed among thioholgamide derivatives: thiazoline heterocycles, which have not yet been reported for thioamitides, and S-methylmethionine, which is very rare in nature. The obtained library was subsequently used for thioholgamide SAR studies and stability assays.


Production of alkaloids and differentiation in a submerged culture of Claviceps purpurea (Fr.) Tul.
The submerged culture of the Claviceps purpurea strain studied was polymorphous. In the process of alkaloid synthesis, cytodifferentiation preceded biochemical differentiation. The onset of the alkaloid phase was characterized by: predominance of chlamydospores in the culture, the presence of vegetative cells with reduced or arrested proliferation, maximum acetylCoA carboxylase activity, the maximum amount of total fatty acids, an over-average cell pool tryptophan level and minimum tryptophan synthetase activity. Intracellular ricinoleic acid was an indicator of differentiation of the culture towards alkaloid formation and also of alkaloid synthesis. The cytodifferentiation period in the initial phases of fermentation, when the cell has several alternative possibilities of development, is regarded as the most sensitive sector of the regulatory mechanisms of alkaloid formation.