Aortic coarctation diagnosed in a hypertensive child undergoing Doppler sonography for suspected renal artery stenosis.
A 5-year-old girl presented with hypertension, with no perceived blood pressure differential between the lower and upper extremities. Doppler ultrasound revealed a tardus-parvus pattern with diminished systolic acceleration and peak systolic velocities in the abdominal aorta and both main renal arteries. Doppler interrogation of the suprasternal aorta showed a normal waveform, suggesting a partial obstruction distally. Echocardiography and aortography confirmed severe discrete aortic coarctation with transverse arch hypoplasia. Because classic findings of aortic coarctation may not be present, especially in the older child, the radiologist must be aware that a tardus-parvus Doppler waveform in the abdominal aorta and bilateral renal arteries is suggestive of proximal aortic stenosis, which may be localized by spectral Doppler of the aortic arch.


On the use of regular solution theory as a theoretical frame for the analysis of membrane phenomena.
The structural heterogeneity of the phospholipid membrane causes difficulties in the analysis of membrane functions. These difficulties can be overcome by using probes which dissolve preferentially into one of the regions, provided that a general theory correlating probe behaviour to membrane structure exists. The use of regular solution theory (RST) as a theoretical frame for membrane analysis is examined below, and it is concluded that some, but not all, of the relations furnished by the theory are useful for membrane analysis. Using these relations, it is concluded that the hydrophobic region of the membrane has a stabilizing effect. The polar region is less stable and changes faster than the hydrophobic region. Diffusion rates are smaller in the hydrophobic region.


A simple QD-FRET bioprobe for sensitive and specific detection of hepatitis B virus DNA.
We report here a simple quantum dot-FRET (QD-FRET) bioprobe based on fluorescence resonance energy transfer (FRET) for the sensitive and specific detection of hepatitis B virus DNA (HBV DNA). The proposed one-pot HBV DNA detection method is very simple, rapid and convenient due to the elimination of the washing and separation steps. In this study, the water-soluble CdSe/ZnS QDs were prepared by replacing the trioctylphosphine oxide on the surface of QDs with mercaptoacetic acid (MAA). Subsequently, DNA was attached to QDs surface to form the functional QD-DNA bioconjugates by simple surface ligand exchange. After adding 6-carboxy-X-rhodamine (ROX)-modified HBV DNA (ROX-DNA) into the QD-DNA bioconjugates solution, DNA hybridization between QD-DNA bioconjugates and ROX-DNA was formed. The resulting hybridization brought the ROX fluorophore, the acceptor, and the QDs, the donor, into proximity, leading to energy transfer from QDs to ROX. When ROX-DNA was displaced by the unlabeled HBV DNA, the efficiency of FRET was dramatically decreased. Based on the changes of both fluorescence intensities of QDs and ROX, HBV DNA could be detected with high sensitivity and specificity. Under the optimized conditions, the linear range of HBV DNA determination was 2.5 - 30 nmol L(-1), with a correlation coefficient (R) of 0.9929 and a limit of detection (3σ black) of 1.5 nmol L(-1). The relative standard deviation (R.S.D.) for 12 nmol L(-1) HBV DNA was 0.9% (n = 5). There was no interference to non-complementary DNA. Time-resolved fluorescence spectra and fluorescence images were performed to verify the validity of this method and the results were satisfying.


Participation of calcium in flagellar shortening and regeneration in Chlamydomonas reinhardii.
Cation chelators cause flagellar shortening in Chlamydomonas reinhardii. Most effective are EDTA and EGTA (1 mM) but pyrophosphate (10 mM) also is effective. Addition of 5 mM Ca2+ after shortening caused by 4 mM EGTA results in flagellar regeneration. Other divalent cations can replace Ca2+ with the following relative activities: Ca2+ greater than Sr2+ = Mn2+ much greater than Ba2+ = Mg2+. Although the specific ion requirement to reverse shortening is not clear, it is possible that all of the ions act by displacing one bound cation, presumably Ca2+. A specific requirement for Ca2+ in flagellar regeneration could be demonstrated, however, because as little as 50 microM EGTA in the presence of 500 microM Mg2+ delayed regeneration and prevented full regeneration. Ca2+ at 100 microM overcame this inhibition.


Validation of a Turkish Version of the Athlete Food Choice Questionnaire.
There are multiple influences on food choice for athletes. The aim of this study was to assess the validity and reliability of a Turkish Athlete Food Choice Questionnaire (Turkish-AFCQ) and describe the main factors influencing food choices. A multi-step process of language and content validation, Explanatory Factor Analysis, Confirmatory Factor Analysis, and test-retest reliability were used to examine factorial structure and construct validity (convergent and discriminant) and reliability (internal and external). The translated Turkish-AFCQ was administered to 446 athletes (59% male, median age = 21 years) from a variety of sports. The original nine-factor structure was validated, external reliability was acceptable, and all factors achieved acceptable discriminate validity. Convergent validity and internal reliability received tenable-ideal ratings for seven and eight factors, respectively. Interpretation and future application are discussed for low-performing factors 'food and health awareness' and 'influence of others'. The factor most frequently (never 1-always 5) influencing choices was 'performance' (Md = 4.33) and the least was both the 'influence of others' and 'food values and beliefs' (Md = 2.67). The Turkish-AFCQ can be used to expand researchers' and practitioners' understanding of the relative influence multiple factors have on food choices, and this study provides a model for AFCQ linguistic translation and validation.


Investigation of Microbial Diversity in Geothermal Hot Springs in Unkeshwar, India, Based on 16S rRNA Amplicon Metagenome Sequencing.
Microbial diversity in geothermal waters of the Unkeshwar hot springs in Maharashtra, India, was studied using 16S rRNA amplicon metagenomic sequencing. Taxonomic analysis revealed the presence of Bacteroidetes, Proteobacteria, Cyanobacteria, Actinobacteria, Archeae, and OD1 phyla. Metabolic function prediction analysis indicated a battery of biological information systems indicating rich and novel microbial diversity, with potential biotechnological applications in this niche.


Mechanisms of platelet adhesion and aggregation: an update.
A hemostatic plug is initially composed of an adherent layer of platelets, but it is subsequent platelet aggregation that stems the flow of leaking blood. Unlike platelet adhesion--which is a passive process--platelet aggregation is active, requiring ongoing platelet metabolism and stimulation by one or more specific agonists.


Time course of skin rash, computed tomography findings, and viral load in a rheumatoid arthritis patient with severe varicella pneumonia.
Varicella-zoster virus (VZV) infection in adults or immunocompromised patients has a more severe presentation compared to the mild disease in children. To the best of our knowledge, no reports have described the clinical course of VZV pneumonia focusing on time course of skin rash, chest computed tomography (CT) findings, and viral load. Furthermore, no reports have described the reactivation of human herpes virus 6 (HHV-6) in VZV pneumonia. Here, we report a case of severe VZV pneumonia that resulted in reactivation of HHV-6 in a patient with rheumatoid arthritis (RA). A 66-year-old female treated for RA was admitted to our hospital with papules. Her chest CT showed granular infiltrates, micronodules, and ground-glass opacities. The day after admission, because the typical skin rashes and chest CT findings were observed, she was diagnosed with VZV pneumonia and treated with acyclovir. Her skin rash then crusted over five days and entered the healing process, whereas it took approximately two weeks for her respiratory condition and chest CT findings to improve. In addition, VZV deoxyribonucleic acid (DNA) gradually decreased with treatment. On the 34th day of admission, VZV DNA was not found in the serum sample but remained in the sputum sample. Furthermore, although reactivation of HHV-6 was observed, viremia resolved without treatment. Clinicians should be able to recognize the differences in the improvement of skin rashes, respiratory status, and chest CT findings. In addition, treatment for HHV-6 reactivation should be carefully determined for each case.


Probiotic and intra-nasal oxytocin combination therapy on autonomic function and gut-brain axis signaling in young children and teens with autism spectrum disorder.
Autonomic dysfunction has been widely studied in individuals with autism spectral disorder (ASD); however, the autonomic response to probiotic and oxytocin (OT) combination intervention has not yet been explored. We conducted the present study that includes 35 individuals with ASD aged 3-20 years to explore autonomic responses to daily Lactobacillus plantarum probiotic supplementation and OT nasal spray treatment both alone and in combination. We identified significant improvements in autonomic indices from subjects receiving combination treatment relative to those receiving placebo. Parameters that were observed to improve following combination treatment are time domain metrics of heart rate variability (HRV), including the root mean square of successive differences between normal heartbeats (RMSSD), standard deviation of normal-to-normal R-R intervals (SDNN), and proportion of the number of pairs of adjacent NN intervals that differ by more than 50ms (pNN50, p < 0.05). Furthermore, individuals that received either probiotics or OT alone demonstrated fewer changes in RMSSD, pNN50, and SDNN. Several parameters that demonstrated significant improvements in combination therapy were found to be correlated with baseline levels of OT (LF power: r = -0.86, p = 0.024; mean HR: r = 0.89, p = 0.012). Additionally, Social Responsiveness Scale (SRS) raw total scores (mean HR, r = 0.86, p = 0.024) and Aberrant Behavior Checklist (ABC) raw total scores (mean HR r = 0.94, p = 0.017) were correlated with mean heart rate (HR) and HRV-derived parameters. These results provide further evidence of synergy of probiotic and OT combination and help us gain a better understanding of the role of the gut-brain axis in ASD phenotypes and pathogenesis.


Induction of chromosomal aberrations and sister chromatid exchange in vivo and in vitro by the insecticide cypermethrin.
The induction of chromosomal aberrations and sister chromatid exchange in vivo in mouse spleen and bone marrow as well as in vitro in cultured mouse spleen cells by the insecticide 'Cypermethrin' (cis-trans 1:1) was investigated. The percentage of chromosomal aberrations in the spleen and in the bone marrow as almost the same and reached its maximum 6 h following i.p. injection. The aberrations induced were chromatid and chromosome gaps, fragments and tetraploidy. The insecticide caused a significant and dose-dependent increase in the frequency of sister chromatid exchanges (SCEs) in mouse bone-marrow cells: it reached 11.12 +/- 0.05 per cell after treatment with Cypermethrin at 300 mg kg-1 body wt. compared with 3.7 +/- 0.14 per cell and 4.4 +/- 0.26 per cell in the solvent and control, respectively. The percentage of viable cells in mouse spleen cell cultures reached 87.4% and 99.9% relative to the control after treatment of the cell cultures with 10(-3) and 10(-7) Cypermethrin, respectively. All the tested concentrations of Cypermethrin (0.25-400 micrograms ml-1) induced a high percentage of metaphases with chromosomal aberrations after 4 h of treatment. The mean frequency of SCEs per cell reached 15.1 +/- 0.05 after treatment with Cypermethrin at 4.00 micrograms ml-1 compared with 8.6 +/- 0.23 and 5.9 +/- 0.39 in the solvent and control, respectively. The results indicate that Cypermethrin is genotoxic in mouse spleen and bone marrow as well as in cultured mouse spleen cells.


[Intracranial hypotension with subdural hematoma following lumbar puncture: case report].
Lumbar puncture is a common procedure highly contributive to neurological diagnosis. It can also cause serious adverse side effects including subdural hematoma and intracranial hypotension as illustrated by this case report. A 38-year-old women presented severe intracranial hypotension after a lumbar puncture. Magnetic resonance imaging was compatible with intracranial hypotension and revealed an acute subdural hematoma with midline deviation. A first blood patch was unsuccessful. Symptom relief was achieved with a second patch. The patient was, then, discharged but developed recurrent headache subsequent to the transformation from acute to chronic subdural hematoma. Surgical drainage was required. The postoperative imaging and physical examination returned to normal and the patient was discharged with no recurrence. The serious adverse effects of lumbar puncture is an easy and common medical procedure that must be kept in mind.


Estrogen therapy attenuates adiposity markers in spontaneously hypertensive rats.
Ovarian hormones modulate the metabolism of adipose cells and present a protective effect against hypertension. The aim of this study was to compare the effect of estradiol on adiposity markers in spontaneously hypertensive rats. Ovariectomized spontaneously hypertensive rats treated with estradiol (5 μg/100 g/day), three weeks after ovariectomy, presented decreased blood pressure and insulin levels and increased hepatic glycogen content. Periuterine or mesenteric adipocytes from treated animals were smaller as compared to vehicle treated group, whereas no differences were observed in relation to the number of cells. Basal rates of glycerol release were higher only in periuterine adipocytes of treated rats. The increment of glycerol release over basal values in response to isoproterenol was 400% and 440%, 283% and 330% for vehicle and estradiol treated periuterine and mesenteric adipocytes, respectively. The estradiol treated group was more sensitive to insulin inhibition of isoproterenol-stimulated lipolysis than the control animals. The lipoprotein lipase activity decreased after treatment, only in periuterine adipose tissue. Estradiol administration increased basal and insulin-stimulated rates of glucose transport in adipocytes of both sites, although the values obtained by periuterine were higher than those observed for mesenteric adipocytes. Both adipose tissues from treated animals exhibited a decreased expression of the peroxisome proliferator-activated receptor-γ, but an increased expression of peroxisome proliferator-activated receptor-α in liver. These findings suggest that estrogen administration attenuates adiposity markers of spontaneously hypertensive rats as a result of the decreased expression levels of peroxisome proliferator-activated receptor-γ in adipose tissue and increased expression of peroxisome proliferator-activated receptor-α in liver.


Sildenafil therapy in patients with sickle cell disease and pulmonary hypertension.
Pulmonary hypertension is a frequent complication of sickle cell disease that is associated with haemolysis, impaired nitric oxide bioavailability and high mortality. We sought to evaluate the safety and efficacy of selective pulmonary vasodilators and antiproliferative agents in this at-risk population. After optimising sickle cell disease therapy to stabilise haemoglobin and fetal haemoglobin levels, we evaluated the safety and efficacy of sildenafil in 12 patients with sickle cell disease and pulmonary hypertension. Sildenafil therapy (mean duration 6 +/- 1 months) decreased the estimated pulmonary artery systolic pressure [50 +/- 4 to 41 +/- 3 mmHg; difference 9 mmHg, 95% confidence interval (CI): 0.3-17, P = 0.043] and increased the 6-min walk distance (384 +/- 30 to 462 +/- 28 m; difference 78 m, 95% CI: 40-117, P = 0.0012). Transient headaches occurred in two patients and transient eye-lid oedema in four patients. No episodes of priapism occurred in the three men in the study; two of them were on chronic exchange transfusions and one had erectile dysfunction. (1) sickle cell disease patients with anaemia and pulmonary hypertension have significant exercise limitation; (2) the 6-min walk distance may be a valid endpoint in this population; (3) therapy with sildenafil appears safe and improves pulmonary hypertension and exercise capacity. Additional phase I studies in males with sickle cell disease followed by phase II/III placebo controlled trials evaluating the safety and efficacy of sildenafil therapy in sickle cell disease patients with pulmonary hypertension are warranted.


Migratory properties of cultured olfactory ensheathing cells by single-cell migration assay.
Olfactory ensheathing cells (OECs) are a unique type of glial cells that have axonal growth-promoting properties. OEC transplantation has emerged as a promising experimental therapy of axonal injuries and demyelinating diseases. However, some fundamental cellular properties of OECs remain unclear. In this study, we found that the distinct OEC subpopulations exhibited different migratory properties based on time-lapse imaging of single isolated cells, possibly due to their different cytoskeletal organizations. Moreover, OEC subpopulations displayed different attractive migratory responses to a gradient of lysophosphatidic acid (LPA) in single-cell migration assays. Finally, we found that OEC subpopulations transformed into each other spontaneously. Together, these results demonstrate, for the first time to our knowledge, that distinct OEC subpopulations display different migratory properties in vitro and provide new evidence to support the notion of OECs as a single cell type with malleable functional phenotypes.


Safety evaluation of proanthocyanidin-rich extract from grape seeds.
Proanthocyanidins, extracted from grape seeds, are widely used mainly as nutritional supplements. However, there has not been a systematic report to investigate toxicological studies on proanthocyanidins, especially in oral administration. In our studies, proanthocyanidin-rich extract from grape seeds was subjected to a series of toxicological tests to document its safety for use in various foods. The grape seed extract (GSE) was examined for acute and subchronic oral toxicity using Fischer 344 rats and for mutagenic potential by the reverse mutation test using Salmonella typhimurium, the chromosomal aberration test using CHL cells, and the micronucleus test using ddY mice. No evidence of acute oral toxicity at dosages of 2 and 4 g/kg, and no evidence of mutagenicity in the above tests was found. Administration of GSE as a dietary admixture at levels of 0.02, 0.2 and 2% (w/w) to the rats for 90 days did not induce noticeable signs of toxicity. The no-observed-adverse-effect level (NOAEL) of GSE in the subchronic toxicity study was 2% in the diet (equal to 1410 mg/kg body weight/day in males and 1501 mg/kg body weight/day in females). The results of our studies indicate a lack of toxicity and support the use of proanthocyanidin-rich extract from grape seeds for various foods.


BiGRUD-SA: Protein S-sulfenylation sites prediction based on BiGRU and self-attention.
S-sulfenylation is a vital post-translational modification (PTM) of proteins, which is an intermediate in other redox reactions and has implications for signal transduction and protein function regulation. However, there are many restrictions on the experimental identification of S-sulfenylation sites. Therefore, predicting S-sulfoylation sites by computational methods is fundamental to studying protein function and related biological mechanisms. In this paper, we propose a method named BiGRUD-SA based on bi-directional gated recurrent unit (BiGRU) and self-attention mechanism to predict protein S-sulfenylation sites. We first use AAC, BLOSUM62, AAindex, EAAC and GAAC to extract features, and do feature fusion to obtain original feature space. Next, we use SMOTE-Tomek method to handle data imbalance. Then, we input the processed data to the BiGRU and use self-attention mechanism to do further feature extraction. Finally, we input the data obtained to the deep neural networks (DNN) to identify S-sulfenylation sites. The accuracies of training set and independent test set are 96.66% and 95.91% respectively, which indicates that our method is conducive to identifying S-sulfenylation sites. Furthermore, we use a data set of S-sulfenylation sites in Arabidopsis thaliana to effectively verify the generalization ability of BiGRUD-SA method, and obtain better prediction results.


The use of biostatic human amnion and platelet-rich plasma in topical treatment of toxic epidermal necrolysis-A case report.
Toxic epidermal necrolysis (TEN) (also known as Lyell syndrome) and Stevens-Johnson syndrome (SJS) are life-threatening mucocutaneous blistering diseases. They are characterized by generalized blisters and epidermal inflammation, most likely resulting from the administration or interaction of medicines. To report potential new method in the treatment of TEN. This article presents a case report of a 35-year-old man suffering from TEN covering about 95% of his body surface. Lesions occurred in the patient during antiepileptic therapy, after taking simultaneously amoxicillin (with clavulanic acid) and naproxen followed by lamotrigine treatment. Standard general treatment was performed. Intravenous feeding was necessary. Due to acute respiratory failure, the patient required mechanical ventilation. Two methods were combined in topical treatment: application of platelet-rich plasma (PRP) and a simultaneous biostatic human amnion transplant. In the presented case, the combination of both methods contributed to a significant acceleration of wound healing. After the application of PRP and biostatic amnion transplantation, the healing of wounds on the back and posterior surfaces of the legs was completed after six days. The surgical treatment most probably contributed to a significant acceleration of wound healing. The case report shows that topical TEN/SJS treatment with biostatic human amnion and PRP has a positive clinical effect and may be a new method of treatment of TEN.


Neurologic Toxicities of Immunotherapy.
Immunotherapy has revolutionized treatment of cancer over the past two decades. The antitumor effects of immunotherapy approaches are at the expense of growing spectrum of immune-related adverse events (irAEs) due to cross-reactivity between the tumor and normal host tissue. These adverse events can happen in any organ and range from mild to severe and even life-threatening conditions. While neurological irAEs associated with immune checkpoint inhibitors (CPIs) are rare, they pose a significant challenge in management as the clinical phenotypes are heterogenous and frequently necessitate cessation of therapy and systemic immune suppression and lead to transient functional decline. On the other hand, immune effector cell-associated neurotoxicity (ICANS) is common, frequently occurs in conjunction with cytokine release syndrome (CRS), and poses a significant clinical challenge to the development and widespread use of these effective therapies. Early recognition of these neurological syndromes, timely diagnosis, and thoughtful management are key for further clinical development of these effective therapies in cancer patients. Here, we describe clinical phenotypes of CPI-induced neurological complications and ICANS and discuss steps in clinical monitoring, diagnosis, and effective management.


Interaction of the aminoglycoside antibiotic dihydrostreptomycin with the H+-ATPase of mitochondria.
In this paper a study is presented of the effect of dihydrostreptomycin on the H+-ATPase of the inner mitochondrial membrane. The antibiotic caused at concentrations of 1-5 X 10(-3)M a marked enhancement of the hydrolytic activity of the H+-ATPase complex in intact mitochondria and submitochondrial particles which was accompanied, in the latter, by enhancement of passive transmembrane proton conduction by the complex. The stimulation by dihydrostreptomycin of ATP hydrolysis resulted in a suppression of the sensitivity of this activity to inhibition by oligomycin. On the other hand the dihydrostreptomycin-promoted proton conduction in submitochondrial particles was suppressed by oligomycin. At concentrations above 10(-2)M dihydrostreptomycin caused inhibition of the activity of both membrane bound and isolated H+-ATPase. In submitochondrial particles devoid of the catalytic moiety (F1) of the H+-ATPase complex, dihydrostreptomycin caused partial inhibition of proton conductivity. It is concluded that the antibiotic uncouples the hydrolytic activity of the catalytic moiety (F1) from transmembrane proton conduction by the membrane sector (F0) of the ATPase complex. This effect can be followed at higher concentrations of dihydrostreptomycin by inhibition of the catalytic activity of F1 and, when F1 is removed from the membrane, by inhibition of transmembrane proton conduction by F0.


Clinical outcome and humoral immune responses of β-thalassemia major patients with severe iron overload to SARS-CoV-2 infection and vaccination: a prospective cohort study.
COVID-19 has raised special concern for patients with β-thalassemia major (β-TM) due to frequent comorbidities, regular blood transfusions, and iron overload. However, the exact implications of COVID-19 for patients with β-TM remain uncertain. We aimed to explore the COVID-19 incidence and severity, and the serological response to SARS-CoV-2 infection and vaccination in patients with β-TM. Patients with β-TM (n = 105) and age-matched healthy controls, all individuals of all control groups were health care workers of the hospital, were prospectively enrolled at the haematology department of Al-Shifa hospital in the Gaza Strip from January 1st, 2021 to December 31st, 2021. Data on COVID-19 incidence and severity were analysed, with Alpha, Beta, and Delta SARS-CoV-2 variants dominating at that time. Anti-SARS-CoV-2 IgG antibody levels were measured and compared between study groups. Patients with β-TM showed a higher incidence of SARS-CoV-2 infection than the general population (61.9% vs. 7.1%, p < 0.0001). Most patients with β-TM had asymptomatic (70.8%) or mild disease (26.1%), with no fatalities recorded. COVID-19 illness was more severe among female than male patients with β-TM. Anti-SARS-CoV-2 IgG antibodies were significantly higher in symptomatic patients with β-TM than controls post-infection (geometric mean ÷ geometric standard deviation 1299.0 ÷ 3.3 vs. 555.7 ÷ 2.4 AU/mL, p = 0.009) and post-vaccination (8404.0 ÷ 3.9 vs. 2785.6 ÷ 5.0 AU/mL, p = 0.015). Similar responses were observed when comparing splenectomised to non-splenectomised (both asymptomatic and symptomatic) patients with β-TM post-infection (595.4 ÷ 3.9 vs. 280.7 ÷ 3.5 AU/mL, p = 0.005) and post-vaccination (13,778.2 ÷ 3.2 vs. 4961.8 ÷ 4.1 AU/mL, p = 0.045). This distinctive β-TM cohort exhibited a high susceptibility to SARS-CoV-2 infection but mild disease course. Our findings support favourable serological responses to SARS-CoV-2 infection and to vaccination in patients with β-TM, indicating a potential interplay between iron availability and COVID-19-related immunity. This study was funded by Mr. Hosam and Wasim s. El Helou.


Favorable gradients with the mitroflow aortic valve prosthesis in everyday surgery.
The supra-annular Mitroflow valve has been implanted for over 20 years, preferably in small aortic roots. Early outcomes and gradients in unselected elderly patients receiving aortic valve surgery are reported in this study. Mitroflow valves were implanted in 190 consecutive patients (70% females). Mean age was 75.6 ± 5.5 years, body mass index was 28.2 ± 5.3 kg/m2, and logistic EuroSCORE 17.8 ± 16.5%. There were 170 single, 17 double, and 3 triple valve procedures. Of all, 46.8% of surgeries were performed with coronary artery bypass grafting and 39.5% were performed with isolated aortic valve replacement (AVR). Rates of redo and endocarditic cases were 14.2 and 4.7%. The 19-mm (n = 14), 21-mm (n = 135), and 23-mm (n = 41) valves showed mean gradients of 16.1 ± 7.4 mm Hg, 15.8 ± 7.1 mm Hg, and 11.6 ± 4.1 mm Hg, respectively, before discharge. Maximum gradients were 27.5 ± 13.0, 28.4 ± 12.6, and 21.6 ± 7.6 mm Hg, respectively. Correlation between gradients and sizes was significant. In-hospital mortality was 12.6% overall (6.7% in isolated AVR). The rate of valve-related events was low (mild paravalvular leakage 2.1%, neurologic 3.2%, bleeding 3.2%, atrioventricular block 4.2%, no thrombosis). The Mitroflow valve can be safely implanted in elderly patients undergoing advanced surgical procedures. Gradients were acceptably low even in the smallest valves.


Evaluation of genetic risks of alkylating agents. III. Alkylation of haemoglobin after metabolic conversion of ethene to ethene oxide in vivo.
Male CBA mice, exposed to air contaminated with [14C] labelled ethene, were able to metabolize this olefine to ethene oxide. The amount of epoxide formed was quantitatively determined from the degree of alkylation of cysteine and histidine in haemoglobin. These hydroxyethylated amino acids were determined by ion-exchange chromatography of the labelled products. In a separate experiment the formation of S-(2-hydroxyethyl) cysteine was verified by gas chromatography--mass spectrometry. In addition this cysteine derivative was determined in urine by thin-layer chromatography. For unknown reasons, uninduced mice varied strongly in the extent to which they converted ethene to epoxide.


Individualized Quality Control Plan (IQCP): Is It Value-Added for Clinical Microbiology?
The Center for Medicaid and Medicare Services (CMS) recently published their Individualized Quality Control Plan (IQCP [https://www.cms.gov/regulations-and-guidance/legislation/CLIA/Individualized_Quality_Control_Plan_IQCP.html]), which will be the only option for quality control (QC) starting in January 2016 if laboratories choose not to perform Clinical Laboratory Improvement Act (CLIA) [U.S. Statutes at Large 81(1967):533] default QC. Laboratories will no longer be able to use "equivalent QC" (EQC) or the Clinical and Laboratory Standards Institute (CLSI) standards alone for quality control of their microbiology systems. The implementation of IQCP in clinical microbiology laboratories will most certainly be an added burden, the benefits of which are currently unknown.


Human CYP1B1-dependent genotoxicity of dioxin-like polychlorinated biphenyls in mammalian cells.
Polychlorinated biphenyls (PCBs) are persistent organic pollutants and human carcinogens. It was reported that rat CYP1A1 and catfish CYP1A can hydroxylate 3,3',4,4',5-pentachlorobiphenyl (PCB 126) and 3,3',4,4'-tetrachlorobiphenyl (PCB 77), while potential roles of other CYP1 enzymes in the metabolism of dioxin-like (DL) PCBs remain unconfirmed. In this study, three representative DL-PCBs, i.e., PCB 77, PCB 126, and 3,4,4',5-tetrachlorobiphenyl (PCB 81), were investigated on their genotoxicity in Chinese hamster V79-derived cell lines genetically engineered for the expression of human CYP1A1, 1A2 and 1B1, and in the human hepatoma C3A cell line, which endogenously expresses various CYPs. Under both 6 h/18 h and 18 h/6 h (exposure/recovery) regimes, PCB 77 and 81 induced micronuclei in V79-hCYP1B1 cells at micromolar levels, with slightly higher potency in the latter regime, while they were inactive in the parental V79-Mz cells and the V79-derived cell lines expressing human CYP1A1 and 1A2. However, PCB 126 was negative in each cell line. Likewise, PCB 77 and 81 induced micronuclei formation in C3A cells, which expressed CYP1B1. This effect was blocked by co-exposure to tetramethoxystilbene (30 nM), a selective CYP1B1 inhibitor. Immuno-fluorescent staining of centromere protein B in the micronuclei in PCB-treated cultures showed a predominance of centromere-negative micronuclei, which indicated a clastogenic effect. Moreover, all three PCBs elevated the level of γ-H2AX protein (indicating DNA double-strand breaks) in C3A cells, and these effects were blocked by tetramethoxystilbene (10 nM). This study demonstrates that some DL-PCBs are clastogenic in mammalian cells following metabolic activation by human CYP1B1.


Nomifensine antagonizes the ouabain-induced increase in dopamine metabolites in cerebrospinal fluid of the rat.
The effect of the Na+, K+-ATPase inhibitor, ouabain, on cerebrospinal fluid dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) levels was studied in pentobarbitone-anesthetized rats. An intracerebroventricular injection of ouabain (100 nmol) dramatically increased DOPAC and HVA levels. A dopamine uptake inhibitor, nomifensine (10 mg/kg i.p.) injected prior to ouabain, completely abolished the effect of ouabain on dopamine metabolites. These results are in agreement with the ouabain-induced increase in dopamine efflux described in vitro and favour the role of a carrier-mediated cytosolic release of dopamine.


Online health communities and the patient-doctor relationship: An institutional logics perspective.
Taking an institutional logics perspective, this study investigates how "internet-informed" patients manage tensions between the logic of personal choice and the logic of medical professionalism as they navigate treatment decisions and the patient-doctor relationship. Based on 44 semi-structured interviews with members of an online health community for people with diabetes, this study finds that patients exercise a great deal of agency in evaluating healthcare options not only by activating the logic of personal choice but also by appropriating the logic of medical professionalism. Furthermore, patients are strategic in deciding what community advice to share with their doctor or nurse depending on the healthcare professionals' reaction to the logic of personal choice. In contrast to many previous studies that emphasise patient consumerism fuelled by information on the Internet, this study provides a more nuanced picture of patient-doctor relationship engendered by patients' participation in online health communities.


Reactive intermediates in the oxidation of hydralazine by HOCl: the major oxidant generated by neutrophils.
The use of the antihypertensive hydralazine is associated with an autoimmune syndrome resembling systemic lupus erythematosus. Adverse drug reactions, such as drug-induced lupus, often involve reactive intermediates. Oxidation of hydralazine by liver microsomes or activated leukocytes leads to reactive intermediates that covalently bind to protein and may be involved in hydralazine-induced lupus. Oxidation of hydralazine to a reactive intermediate by cells involved in immune response, such as leukocytes, would be more likely to lead to an autoimmune reaction, such as drug-induced lupus, than would oxidation by cells in the liver. Leukocytes possess a defense system that generates HOCl in response to invading microorganisms. Hydralazine was oxidized to a reactive intermediate by HOCl generated by activated leukocytes. The reactive intermediate was trapped with N-acetylcysteine and the adduct was identified as 1-phthalazylmercapturic acid. The reactive intermediate is likely the diazonium salt of hydralazine. Two stable products were formed in the reaction, phthalazine and phthalazinone. Although phthalazine is oxidized to phthalazinone by HOCl, the rate of the reaction is much too slow to explain the rapid production of phthalazinone. It is more likely that most of the phthalazinone is formed by reaction of the putative diazonium salt with water. We propose that this reactive metabolite is responsible for hydralazine-induced lupus.


Expanding the phenotypic and genetic spectrum of Chinese patients with congenital absence of vas deferens bearing CFTR and ADGRG2 alleles.
Congenital absence of vas deferens (CAVD) is a major cause of obstructive azoospermia. Mutations in CFTR and ADGRG2 are responsible for this disease. However, until now the genetic spectrum of the CFTR and ADGRG2 genes in Chinese population and the reasons of the differences from Caucasian cohorts were not clear. (i) To study the characteristic and functional consequences of CFTR and ADGRG2 mutations in Chinese CAVD patients. (ii) To describe the genetic spectrum of Chinese CAVD patients and explain the reasons of the differences from Caucasian cohorts and Chinese cystic fibrosis (CF) patients. Patients were screened for mutations in CFTR by Sanger sequencing. Patients with only one or no mutations were further investigated by multiplex ligation-dependent probe amplification analysis and direct sequencing of ADGRG2 gene. Bioinformatic analysis and structural modeling of proteins were performed. A total of 28 mutations in CFTR were identified in 72 patients, of which five mutations were novel. Fifty-five patients (76.39%) had CFTR mutations but no indels, among which 80.00% CBAVD patients have at least one CFTR mutation and 66.67% CUAVD have at least one CFTR mutation. Two novel mutations (p.Lys818* and p.Arg1008Gln) in ADGRG2 were detected. These novel mutations were predicted to be damaging by bioinformatics and were absent or extremely low frequency among our controls and databases. The genetic spectrum of Chinese CAVD patients revealed that the most common mutations were c.1210-12T[5], p.Ile556Val and p.Gln1352His, the last two of which were predicted to reduce the domains' contacts and weaken adenosine triphosphate binding. This study illustrates the significance of all exon sequencing in CFTR and ADGRG2. A picture of the genetic spectrum of Chinese CAVD patients and the most common mutations can be described, which are different from Caucasian cohorts and Chinese CF patients.


[Effects of L-arginine on the microcirculation of rat island skin flaps after ischemia- reperfusion].
To investigate the effects of L-arginine on the microcirculation and survival of rat island skin flaps after ischemia-reperfusion. A right lower abdominal island flap was created in SD rats and the microcirculatory blood flow in these flaps measured with laser Doppler velocimetry following L-arginine injection via the contralateral femoral artery. Both NO and malondialdehyde (MDA) levels in the flaps were assayed and the survival of the flaps replanted in situ was evaluated 1 week later. L-arginine treatment caused increase in the microcirculatory blood flow of the flaps and elevation of NO while and decrease of MDA levels. The survival rate of the flaps with L-arginine treatment was significantly higher than the flaps from saline-treated and normal rats. L-arginine can improve the survival of island flap through increasing the microcirculatory blood flow and lessening ischemia-reperfusion injury of the flaps.


Social subordination and scent-marking in male Mongolian gerbils (Meriones unguiculatus).
Mongolian gerbil (Meriones unguiculatus) readily attacks an unfamiliar gerbil intruding into its territory. After several attacks, subordinated intruders seldom scent-mark in the occupied area. This inhibition of scent-marking is a response to stimuli associated with the defended territory, since subordinated males mark normally elsewhere. Previous research suggested that olfactory cues were primarily responsible, but data presented here do not support this. Subordinated males scent-marked as often as controls in a neutral arean contaminated with the dominant animals' bedding odours. Moreover, subordinate males seldom scent-marked in an area resembling the defended territory, even though defeat-related odours were absent. Repeated exposure without attack to the visually similar, but clean, test area did not enhance marking in subordinated males.


Crystallization and preliminary X-ray diffraction studies of leishmanolysin, the major surface metalloproteinase from Leishmania major.
The membrane-bound GPI-anchored zinc metalloproteinase leishmanolysin purified from Leishmania major promastigotes has been crystallized in its mature form. Two crystal forms of leishmanolysin have been grown by the vapor diffusion method using 2-methyl-2,4-pentanediol as the precipitant. Macroseeding techniques were employed to produce large single crystals. Protein microheterogeneity in molecular size and charge was incorporated into both crystal forms. The tetragonal crystal form belongs to the space group P4(1)2(1)2 or the enantiomorph P4(3)2(1)2, has unit cell parameters of a = b = 63.6 A, c = 251.4 A, and contains one molecule per asymmetric unit. The second crystal form is monoclinic, space group C2, with unit cell dimensions a = 107.2 A, b = 90.6 A, c = 70.6 A, beta = 110.6 degrees, and also contains one molecule per asymmetric unit. Both crystal forms diffract X-rays beyond 2.6 A resolution and are suitable for X-ray analysis. Native diffraction data sets have been collected and the structure determination of leishmanolysin using a combination of the isomorphous replacement and the molecular replacement methods is in progress.


Different Interventions for COVID-19 Primary and Booster Vaccination? Effects of Psychological Factors and Health Policies on Vaccine Uptake.
Mitigation of the COVID-19 pandemic requires continued uptake of SARS-CoV-2 vaccines. To increase vaccination intention and uptake, key determinants of primary and booster vaccination need to be understood and potential effects of vaccination policies examined. Using experimental data collected in Germany in February 2022 (N = 2701), this study investigated 1) predictors of primary and booster vaccination and 2) potential effects of policies combining vaccination mandates and monetary incentives. Compared with unvaccinated participants, those with primary vaccination were less complacent, more often understood the collective protection afforded by vaccination, and less often endorsed conspiracy-based misinformation. Compared with participants with primary vaccination, boosted individuals were even less complacent, exhibited fewer conspiracy-based beliefs, perceived fewer constraints by prioritizing vaccination over other things, and more often favored compliance with official vaccination recommendations. Support for and reactance about vaccination mandates depended on vaccination status rather than policy characteristics, regardless of mandate type or incentives (up to 500 EUR). While unvaccinated individuals rejected policy provisions and declined vaccination, boosted individuals indicated mid-level support for mandates and showed high vaccination intention. Among vaccinated individuals, higher incentives of up to 2000 EUR had a considerable positive effect on the willingness to get boosted, especially in the absence of a mandate. While mandates may be needed to increase primary vaccination, our results indicate that financial incentives could be an alternative to promote booster uptake. However, combining both measures for the same target group seems inadvisable in most cases. Unvaccinated individuals and people with primary and booster vaccinations differ on psychological dimensions, calling for tailored immunization campaigns.Vaccination intentions depend on vaccination status rather than on mandatory or incentivizing policies.Incentives are unlikely to persuade unvaccinated individuals but may increase booster uptake.Positive effects of incentives decrease when vaccination is mandatory, advising against combination.


Intravital lipid droplet labeling and imaging reveals the phenotypes and functions of individual macrophages in vivo.
Macrophages play pivotal roles in the maintenance of tissue homeostasis. However, the reactivation of macrophages toward proinflammatory states correlates with a plethora of inflammatory diseases, including atherosclerosis, obesity, neurodegeneration, and bone marrow (BM) failure syndromes. The lack of methods to reveal macrophage phenotype and function in vivo impedes the translational research of these diseases. Here, we found that proinflammatory macrophages accumulate intracellular lipid droplets (LDs) relative to resting or noninflammatory macrophages both in vitro and in vivo, indicating that LD accumulation serves as a structural biomarker for macrophage phenotyping. To realize the staining and imaging of macrophage LDs in vivo, we developed a fluorescent fatty acid analog-loaded poly(lactic-co-glycolic acid) nanoparticle to label macrophages in mice with high efficiency and specificity. Using these novel nanoparticles, we achieved in situ functional identification of single macrophages in BM, liver, lung, and adipose tissues under conditions of acute or chronic inflammation. Moreover, with this intravital imaging platform, we further realized in vivo phenotyping of individual macrophages in the calvarial BM of mice under systemic inflammation. In conclusion, we established an efficient in vivo LD labeling and imaging system for single macrophage phenotyping, which will aid in the development of diagnostics and therapeutic monitoring. Moreover, this method also provides new avenues for the study of lipid trafficking and dynamics in vivo.


Experimental investigation on regulated and unregulated emissions of a diesel engine fueled with ultra-low sulfur diesel fuel blended with biodiesel from waste cooking oil.
Experiments were conducted on a 4-cylinder direct-injection diesel engine using ultra-low sulfur diesel, bi oesel and their blends, to investigate the regulated and unregulated emissions of the engine under five engine loads at an engine speed of 1800 rev/min. Blended fuels containing 19.6%, 39.4%, 59.4% and 79.6% by volume of biodiesel, corresponding to 2%, 4%, 6% and 8% by mass of oxygen in the blended fuel, were used. Biodiesel used in this study was converted from waste cooking oil. The following results are obtained with an increase of biodiesel in the fuel. The brake specific fuel consumption and the brake thermal efficiency increase. The HC and CO emissions decrease while NO(x) and NO(2) emissions increase. The smoke opacity and particulate mass concentrations reduce significantly at high engine load. In addition, for submicron particles, the geometry mean diameter of the particles becomes smaller while the total number concentration increases. For the unregulated gaseous emissions, generally, the emissions of formaldehyde, 1,3-butadiene, toluene, xylene decrease, however, acetaldehyde and benzene emissions increase. The results indicate that the combination of ultra-low sulfur diesel and biodiesel from waste cooking oil gives similar results to those in the literature using higher sulfur diesel fuels and biodiesel from other sources.


Ibotenic acid induced demyelination in the central nervous system: a consequence of a local inflammatory response.
We examined the effects of injections of ibotenic acid into the medial septum (MS), dorsal lateral geniculate nucleus (dLGN), caudate-putamen (CP) or fornix-fimbria (FF) on fibres close to the injection site. Injections into the MS and dLGN resulted in demyelination. The area of demyelination correlated with the area of maximal gliosis. The major cell type in the area of gliosis were cells of haemopoietic origin, as revealed by using monoclonal antibodies (Mabs). Demyelination was not observed in the CP or FF. Axonal transport in fibres en passage through the dLGN lesion was also disrupted following injections of horseradish peroxidase (HRP) into the eye contralateral to the lesion. These results show that when ibotenic acid induces cell death it can secondarily damage myelin sheaths and disrupt axonal transport in areas containing diffuse fibre systems. We suggest that this is due to a non-specific effect of the inflammatory response.


Comparison of the Efficacy of Endoscopic Radial Incision and Cutting Procedure and Endoscopic Balloon Dilation for Benign Anastomotic Stricture After Low Anterior Resection Combined With Preventive Loop Ileostomy in Rectal Cancer.
Endoscopic radial incision and cutting procedure is a notable technique in the treatment of benign anastomotic strictures after low anterior resection in rectal cancer. However, the efficacy and safety of the endoscopic radial incision and cutting procedure and traditional endoscopic balloon dilation remain unknown. To compare the efficacy and safety of the endoscopic radial incision and cutting procedure and endoscopic balloon dilation in patients with anastomotic stricture after low anterior resection. Rectal cancer patients with anastomotic stricture after low anterior resection combined with synchronous preventive loop ileostomy between January 2014 and June 2021 were retrospectively collected. These patients underwent the endoscopic radial incision and cutting procedure or endoscopic balloon dilation as an initial treatment. The clinicopathological baseline data of the patients, endoscopic surgery success rate, complications, and restricture rate were analyzed. This study was conducted at Nanfang Hospital in China. A total of 30 patients were eligible after reviewing the medical records. Twenty patients underwent endoscopic balloon dilation, and 10 patients underwent endoscopic radial incision and cutting procedure. The adverse event rate and stricture recurrence rate. There were no significant differences in patient demographics or clinical features. No adverse events occurred in either of the 2 groups. The mean operation time was 18.9 ± 3.6 minutes in the endoscopic balloon dilation group and 10.2 ± 3.3 minutes in the endoscopic radial incision and cutting procedure group ( p < 0.001). The stricture recurrence rates between the endoscopic balloon dilation group and the endoscopic radial incision and cutting procedure group were significantly different (44.4% vs 0%; p = 0.025). This was a retrospective study. The endoscopic radial incision and cutting procedure is safe and more efficacious than endoscopic balloon dilation for anastomotic stricture after low anterior resection combined with synchronous preventive loop ileostomy in rectal cancer.


Enhancing International Cancer Organization Collaborations: King Hussein Cancer Center and Princess Margaret Cancer Centre Model for Collaboration.
Collaborative partnerships, which link two health organizations with shared characteristics to achieve common goals and to improve healthcare quality, are becoming increasingly common in oncology. The purpose of this study is to review the collaboration between King Hussein Cancer Center (KHCC) and Princess Margaret Cancer Centre (PM). The context, input, process, and product (CIPP) model, a quasi-experimental form of program evaluation, has been applied to the KHCC-PM collaboration. This model is well suited to evaluate complex collaborations as it does not assume linear relationships. Data sources include stakeholders' judgements of the collaboration, assessment of achievements, and informal interviews with key participants involved in the program. KHCC and PM are recognized as high-caliber comprehensive cancer centers, with a common goal of delivering high-quality care to patients. Through personal relationships among faculty in the centers and the perceived opportunities for mutual benefit, KHCC and PM signed a memorandum of understanding in 2013 to enter into a formal partnership. This partnership has been an evolving process that started with collaboration on education and grew to include clinical care. Research is an area for potential future collaboration. Enabling factors in the collaboration include dedication of individuals involved, trusting relationships amongst faculty, and the reciprocal nature of the relationship. Challenges have been financial, competing interests, and the absence of a successful collaborative model to follow. The KHCC and PM collaboration has been successful. A strategic plan is being developed and followed to guide areas of expansion.


Graphene oxide and self-avoiding molecular recognition systems-assisted recombinase polymerase amplification coupled with lateral flow bioassay for nucleic acid detection.
A new nucleic acid detection technique, termed Nano-SAMRS-RPA, is reported which employed carbon nanomaterial (graphene oxide, GO) and self-avoiding molecular recognition systems (SAMRS) to improve the specificity of recombinase polymerase amplification (RPA). In the presence of GO and SAMRS primers, the assay artifacts, including primer-dimers, nonspecific products, off-target hybrids, and non-canonical folds, are completely suppressed and eliminated, which makes the creation of RPA-based methods faster by simplifying the primer design and eliminating the need for primer optimization and complex probe. Moreover, a lateral flow bioassay (LFB) was also devised for simply and rapidly indicating the Nano-SAMRS-RPA results. Particularly, the new detection system only requires a single-labeled primer, eliminating the false-positive result from hybridization (the labeled probe and reverse primer) and the use of real-time instrument, more complex enzymatic solutions, and probes. As a result, GO, SAMRS primers, and LFB convert RPA from a technique suited only for the research laboratory into one that has a practical value in clinical settings, field environments, and at points-of-care testing. Human papillomaviruses (HPV) genotypes 16 and 18 were applied as model analytes to test the assay's availability. The initial data indicated that Nano-SAMRS-RPA could detect down to 10 copies per reaction, and the sensitivity (14/14 samples collected from HPV16 and HPV 18 patients) and specificity (75/75 samples collected from non-HPV patients) for clinical sample detection were 100%. The proof-of-concept technique can be reconfigured to detect various nucleic acid sequences by redesigning the specific RPA primers.Graphical abstract.


Risk factors and treatment of childhood and adolescent Burkitt lymphoma/leukaemia.
Burkitt lymphoma/leukaemia is the most common (40%) form of non-Hodgkin lymphoma that occurs in children and adolescents. The prognosis of advanced (disseminated) Burkitt lymphoma/leukaemia in children and adolescents three decades ago had a 5-year event-free survival (EFS) of <40%, and required combination chemotherapy and radiation therapy over a 1-2 year period. Currently, the prognosis for the same advanced stage has a 5-year EFS of 85-90% with <6 months of chemotherapy only. Radiation therapy has been eliminated for children and adolescents with Burkitt lymphoma/leukaemia except in emergencies, such as superior vena cava syndrome and acute neurological impairment or in patients with relapse/progression. Current risk factors in the prognosis of childhood and adolescent Burkitt lymphoma/leukaemia include: lactate dehydrogenase level ≥ 2× the upper normal limit at diagnosis, bone marrow and central nervous system involvement, poor response to cyclophosphamide, vincristine and prednisone reduction therapy and poor risk cytogenetics. New and novel therapeutic approaches include monoclonal antibody (anti-CD20) therapy, targeted cellular immune therapy and small molecule inhibitors. Future strategies should include improved staging and risk classification, reduction of cytotoxic chemotherapy, the investigation of targeted therapy, an increased understanding of the underlying biology of Burkitt lymphoma/leukaemia, strategies for prevention and approaches to reduce acute and chronic toxicities.


High co-expression of vascular endothelial growth factor receptor-1 and Snail is associated with poor prognosis after curative resection of hepatocellular carcinoma.
VEGFR-1-mediated signaling promotes invasiveness by direct tumor activation in some cancers. However, VEGFR-1 expression and its relationship with clinical features and prognosis in HCC remained unclear. Overexpression of Snail is common in HCC and associated with poorer prognosis. Therefore, expression of VEGFR-1 and Snail was investigated in HCC cell lines and tissue specimens in our study, and special attention was paid to evaluating the role of VEGFR-1 expression in prognosis of HCC. Western blot and immunofluorescence were used to detect expression of VEGFR-1, Snail and MMP-9 in 4 HCC cell lines, respectively. Moreover, expression of these proteins was confirmed on the samples from 95 HCC patients who underwent curative resection using immunohistochemistry. ROC and survival analysis determined the predictive values of parameters and the association with survival. HCC cell lines with a higher VEGFR-1 expression were more invasive. Both VEGFR-1 and Snail expressions were significantly higher in HCC tissues than in non-cancerous tissues. High-expression VEGFR-1 and Snail, associated with adverse clinical features, were independent prognostic factors for RFS and OS (P=0.023 and P=0.044, respectively). Positive correlation was found between VEGFR-1 and Snail or MMP-9 (r=0.418 and r=0.232, respectively, P<0.05 for both) in cancerous tissues. The combination of VEGFR-1 and Snail gave a better power to predict patients' recurrence and death (P<0.001 for both). High VEGFR-1 expression, distinctively expressed in the cytomembrane of HCC cells, was associated with HCC progression and worse outcome. High co-expression of VEGFR-1 and Snail may be a novel prognostic marker for HCC, especially in recurrence.


Impact of nationwide centralization of pancreaticoduodenectomy on hospital mortality.
The impact of nationwide centralization of pancreaticoduodenectomy (PD) on mortality is largely unknown. The aim of this study was to analyse changes in hospital volumes and in-hospital mortality after PD in the Netherlands between 2004 and 2009. Nationwide data on International Classification of Diseases, ninth revision (ICD-9) code 5-526 (PD, including Whipple), patient age, sex and mortality were retrieved from the independent nationwide KiwaPrismant registry. Based on established cut-off points of annually performed PDs, hospitals were categorized as very low (fewer than 5), low (5-10), medium (11-19) or high (at least 20) volume. A subgroup analysis based on a cut-off age of 70 years was also performed. Some 2155 PDs were included. The number of hospitals performing PD decreased from 48 in 2004 to 30 in 2009 (P = 0·011). In these specific years, the proportion of patients undergoing PD in a medium- or high-volume centre increased from 52·9 to 91·2 per cent (P < 0·001). Nationwide mortality rates after PD decreased from 9·8 to 5·1 per cent (P = 0·044). The mortality rate during the 6-year period was 14·7, 9·8, 6·3 and 3·3 per cent in very low-, low-, medium- and high-volume hospitals respectively (P < 0·001). The difference in mortality between medium- and high-volume centres was statistically significant (P = 0·004). The volume-outcome relationship was not influenced by age (P = 0·467). The mortality rate after PD in patients aged at least 70 years was 10·4 per cent compared with 4·4 per cent in younger patients (P < 0·001). With nationwide centralization of PD, the in-hospital mortality rate after this procedure decreased. Further centralization of PD is likely to decrease mortality further, especially in the elderly.


Absence of rapid terpene turnover in several diverse species of terpene-accumulating plants.
Terpenes are commonly believed to undergo rapid metabolic turnover in plants, but the evidence for this process comes largely from studies that used detached organs or applied radiolabeled precursors in unnatural ways. When 14CO2 pulse labeling experiments were carried out with intact plants of four taxonomically distant, terpene-accumulating species, no significant turnover of monoterpenes, sesquiterpenes or diterpenes was detected in young foliage over a two week period after exposure to 14CO2. These results are consistent with those of other investigations performed under physiologically realistic conditions, and caution against the uncritical incorporation of turnover into models or theories concerning plant chemical defense.


Side effects of intravenous immunoglobulins in neurological autoimmune disorders--a prospective study.
The increased use of intravenous immunoglobulins (IVIg) in the treatment of neurological autoimmune diseases has led to more awareness of adverse reactions. We studied prospectively the side effects of IVIg during 84 treatment courses with a total of 341 infusions under routine clinical conditions. Mild reactions were common. Headache was noted most often, occurring during 30% of treatment courses. There were three severe adverse events (3.6% of all treatment courses) that led to discontinuation of the treatment, namely thrombosis of the jugular vein, allergic reaction and retrosternal pressure. Significant changes in laboratory findings were seen for leucocytes, erythrocytes, haematocrit, haemoglobin, ALAT and ASAT. None of these changes were clinically relevant. The elevation of liver enzymes was dependent on the IVIg preparation used, while there was no association with the underlying disease, age, or gender of the patient. In conclusion, this prospective study confirms the high frequency of mild, self-limited side effects of IVIg. Elevation of liver enzymes may possibly be associated with certain IVIg preparations. Bearing these complications in mind, this prospective study supports the notion that IVIg can generally be regarded as safe, leading to severe adverse events during only 3 (0.9%) of 341 infusions (or 3 of 84 treatment courses, 3.6 %). However, careful monitoring for severe side effects remains mandatory, and we propose that laboratory findings like full blood count, renal and liver function should be monitored routinely.


Alcohol-related stimuli reduce inhibitory control of behavior in drinkers.
Poor behavioral control and heightened attentional bias toward alcohol-related stimuli have independently received considerable attention in regard to their roles in alcohol abuse. Theoretical accounts have begun to speculate as to potential reciprocal interactions between these two mechanisms that might promote excessive alcohol consumption, yet experimental evidence is lacking. The objective of the study was to integrate these two lines of research through the development of a novel laboratory task that examines the degree to which alcohol cues serve to disrupt mechanisms of behavioral control. Fifty adult drinkers were recruited to perform the attentional bias-behavioral activation (ABBA) task. The ABBA task, an adaptation of traditional cued go/no-go tasks, is a reaction time model that measures the degree to which alcohol-related stimuli can increase behavioral activation of a drinker and reduce the ability to inhibit inappropriate responses. Participants also completed a novel measure of attentional bias, the scene inspection paradigm (SIP), that measures fixation time on alcohol content imbedded in complex scenes. As hypothesized, the proportion of inhibitory failures on the ABBA task was significantly higher following alcohol images compared to neutral images. Correlational analyses showed that heightened attentional bias on the SIP was associated with greater response activation following alcohol images on the ABBA task. These findings suggest that alcohol stimuli serve to disrupt mechanisms of behavioral control, and that heightened attentional bias is associated with greater disruption of control mechanisms following alcohol images.


Tissue-Specific RNA Localization in the Uterus During Implantation, Decidualization and Placentation: Technical Nuances of Various Labeling Approaches.
In situ hybridization (ISH) is a sensitive method used to localize a specific sequence of DNA or RNA in biological samples, including cells, tissue sections or whole organs. RNA ISH can be used to determine spatial gene expression using a single-stranded probe with a reverse-complementary sequence. Cell-specific gene expression has been studied using mRNA and protein levels. Signals produced by RNA probes are usually more specific than those produced by antibodies in immunostaining. Currently, ISH is the most widely used method to localize mRNA molecules. Traditionally, probes were labeled with radioactive isotopes, but the cumbersome procedures and potential health risk limit their acceptance. Recently, probes labeled with nonradioactive materials including digoxigenin, biotin and various fluorophores have been developed. The tyramide signal amplification system further enhances the sensitivity of detection. These methods have been applied in numerous studies in various tissues including reproductive organs. This article details three methods of RNA in situ hybridization: radioactive in situ hybridization, digoxigenin in situ hybridization, and digoxigenin-tyramide signal amplification fluorescein in situ hybridization. The pros and cons of each protocol are discussed. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Radioactive in situ hybridization (radioactive-ISH) Basic Protocol 2: Digoxigenin in situ hybridization (DIG-ISH) Basic Protocol 3: Digoxigenin-tyramide signal amplification fluorescein in situ hybridization (DIG-TSA-FISH).


Comparing the Outcomes and Complication Rates of Biologic vs Synthetic Meshes in Implant-Based Breast Reconstruction: A Systematic Review.
This systematic review evaluates all published studies comparing biologic and synthetic meshes in implant-based breast reconstruction (IBBR), to determine which category of mesh produces the most favorable outcomes. Breast cancer is the most common cancer in women globally. Implant-based breast reconstruction is currently the most popular method of postmastectomy reconstruction, and recently, the use of surgical mesh in IBBR has become commonplace. Although there is a long-standing belief among surgeons that biologic mesh is superior to synthetic mesh in terms of surgical complications and patient outcomes, few studies exist to support this claim. A systematic search of the EMBASE, PubMed, and Cochrane databases was performed in January 2022. Primary literature studies comparing biologic and synthetic meshes within the same experimental framework were included. Study quality and bias were assessed using the validated Methodological Index for Non-Randomized Studies criteria. After duplicate removal, 109 publications were reviewed, with 12 meeting the predetermined inclusion criteria. Outcomes included common surgical complications, histological analysis, interactions with oncologic therapies, quality of life measures, and esthetic outcomes. Across all 12 studies, synthetic meshes were rated as at least equivalent to biologic meshes for every reported outcome. On average, the studies in this review tended to have moderate Methodological Index for Non-Randomized Studies scores. This systematic review offers the first comprehensive evaluation of all publications comparing biologic and synthetic meshes in IBBR. The consistent finding that synthetic meshes are at least equivalent to biologic meshes across a range of clinical outcomes offers a compelling argument in favor of prioritizing the use of synthetic meshes in IBBR.


A Virtual Point-of-care Ultrasound Course During the COVID-19 Pandemic.
Due to the COVID-19 pandemic, in-person educational activities for emergency medicine (EM) residents were suspended. As a result, we developed a virtual point-of-care ultrasound (POCUS) course for incoming EM interns consisting of online didactics and faculty-proctored hands-on scan sessions utilizing a video conferencing platform and a handheld smartphone-compatible ultrasound transducer. Learners found the course to be effective in improving their POCUS knowledge and scanning skills. Feedback obtained from this course will allow us to improve future virtual courses.


AAA+ proteins: have engine, will work.
The AAA+ (ATPases associated with various cellular activities) family is a large and functionally diverse group of enzymes that are able to induce conformational changes in a wide range of substrate proteins. The family's defining feature is a structurally conserved ATPase domain that assembles into oligomeric rings and undergoes conformational changes during cycles of nucleotide binding and hydrolysis. Here, we review the structural organization of AAA+ proteins, the conformational changes they undergo, the range of different reactions they catalyse, and the diseases associated with their dysfunction.


Developmental changes in density and distribution of serotoninergic fibers in the chick spinal cord.
Developmental changes of serotoninergic innervation in the chick spinal cord (third lumbosacral segment) were examined with an immunohistochemical technique using an antiserum to serotonin. In the 1-day-old hatched chick, serotoninergic fibers were located in laminae I, II, VII, IX, and X. A large number of serotonin-positive fibers and terminals were found around somal profiles of large neurons and in the neuropil of the medial and lateral parts of the lateral motor column (LMC). In the 1-week-old chick, the density of serotoninergic fibers was greatly increased in the posterior columns, and serotoninergic fibers were most densely aggregated in the dorsolateral part of the LMC. In the 2-week-old chick, a considerable decrease in the density of serotoninergic fibers was observed in the lateral funiculus and the gray matter (laminae I, II, VII, IX, and X). In the LMC, serotonin-positive fibers and terminals were largely absent from the neuropil, but were found preferentially around the somal profiles of large neurons. Between 1 and 2 weeks after hatching the density of varicosities and terminals in the neuropil of the dorsolateral and medial parts of the LMC decreased by 33% and 56%, respectively. In the 3-month-old chick, the density of serotoninergic fibers in laminae I, II, V, VII, and X had increased compared to younger ages. Serotonin-positive fibers were not evenly distributed in the LMC of the adult chicken; rather, they were densely aggregated around the soma and proximal dendrites of motoneurons in the dorsolateral LMC. Many neuronal soma in the medial and intermediate regions of the LMC lacked serotoninergic fibers.


Aortic dissection in Indonesia male: 3 case report.
Aortic dissection (AD) is a life-threatening rare condition caused by a tear in the aortic wall which requires urgent surgery. 3 Indonesian males obtained a CT angiography (CTA) showing a picture of AD which was confirmed using the Stanford and De Bakey classification. The patient was successful in undergoing TEVAR and open-heart surgery which 2 patients survived and 1 patient died. The speed of handling in AD is the key to successful management of AD supported by an understanding of the signs and symptoms and results of thoracoabdominal CTA. The ability to interpret CTA results and understand AD sign symptoms is very helpful in minimizing mortality.


High-flow arteriovenous fistula and hemodynamic consequences at 1 year after kidney transplantation.
There are only scarce data regarding the cardiovascular impact of arteriovenous fistula after kidney transplantation depending on fistula flow. We performed a single-center, prospective, cohort study including 49 patients with a functional fistula at 1 year from kidney transplantation. Patients were convened for a clinical work-up, a biological analysis, a fistula's Doppler ultrasonography and an echocardiography. Main judgment criterion was comparison of echocardiography parameters between patients with relative (fistula flow >1 L/min and a fistula flow/cardiac output ratio >20%), absolute high-flow fistula (fistula flow >2 L/min) and normal-flow fistula. High-flow fistula frequency was 69%. Significantly higher left ventricular end-diastolic and systolic diameters were observed in this group compared with the normal-flow fistula group (53 ± 6 vs. 48 ± 7 mm; p = 0.04 and 33 ± 6 vs. 28 ± 8 mm; p = 0.02) and between the absolute and relative high-flow fistula subgroups (56 ± 6 vs. 51 ± 6 mm; p = 0.009 and 35 ± 6 vs. 31 ± 5 mm; p = 0.01). The study showed no other significant differences. This study showed a significantly higher but not pathological left ventricular end-diastolic and systolic diameters values in patients with high-flow fistula compared with patients with normal-flow fistula and between patients with respectively absolute and relative high-flow fistula.


Glucose-lowering agents and risk of ventricular arrhythmias and sudden cardiac death: A comprehensive review ranging from sulphonylureas to SGLT2 inhibitors.
Type 2 diabetes is associated with a higher risk of cardiac arrhythmias, especially in presence of cardiovascular disease and/or heart failure. Even if atrial fibrillation/flutter episodes are the most frequent and well-studied, ventricular arrhythmias (VA: tachycardia/fibrillation) are more severe and can lead to sudden cardiac arrest/death (SCA/SCD). The effects of glucose-lowering agents on the risk of VA/SCD remain poorly understood. Findings may be derived from experimental animal studies, randomised controlled trials/cardiovascular outcome trials and observational retrospective studies. A higher risk was attributed to hypoglycaemia when induced by insulin or even more critically by sulphonylureas. Insulin-secreting agents seem to be associated with a higher risk of cardiac arrhythmias compared with insulin sensitizers (metformin, thiazolidinediones), yet the risk linked to sulphonylureas remains controverted. Incretin-based therapies (DPP-4 inhibitors and GLP-1 receptor agonists) overall appear to be neutral regarding the risk of cardiac arrhythmias, despite some heterogeneous results. SGLT2 inhibitors appear to reduce the risk of SCA/SCD and possibly VA, yet only a non-significant trend was noticed in most reports. Overall, hazard ratios with SGLT2 inhibitors versus other therapies were lower for SCD (presumably of diverse causes) than for well demonstrated VA episodes. Underlying mechanisms remain uncertain and numerous pleiotropic effects may be involved. Prospective controlled trials and experimental studies specifically devoted to the effects of SGLT2 inhibitors on cardiac arrhythmias are needed to confirm their positive effects in diabetic patients and in individuals with heart failure irrespective of diabetes and, if possible, to carefully dissect the underlying protective mechanisms.


Yield and activity of Autographa californica multicapsid nucleopolyhedrovirus and Phthorimaea operculella granulosis virus in cloned and uncloned cell lines of P. operculella.
Three selected uncloned Pop 2, Pop 3, Pop 4 and two cloned cell lines Pop cl1A and Pop cl2B were derived from the original cell line established from Phthorimaea operculella (ORS-Pop-93). Three new non-selected cell lines ORS-Pop-94A, ORS-Pop-94B and ORS-Pop-95 were also established from embryos of the same insect. Differences in morphology, growth rate and polypeptide profile were determined between these cell lines. All the cell lines were susceptible to the Autographa californica nucleopolyhedrovirus (AcMNPV). The cloned cell lines produced higher levels of AcMNPV (TCID-50 and PIB) than the parental cells and at the same rate as the Sf9 reference cell line. Substantial amounts of viral DNA were synthesized in the clone Pop cl 2B after infection with the granulosis virus of the potato tuber moth P. operculella (PTMGV) and a complete multiplication was obtained in the ORS-Pop-95 cell line. The comparison between Pop cell lines which support limited or complete replication of certain baculoviruses can offer insights into some of the molecular barriers which restrict the host range of these viruses. These cell lines with variable susceptibility to baculoviruses could also be used for in vitro recombinations, increasing their virus host range to be used for the control of this pest.


Megasession: excision of numerous skin cancers in a single session.
A large number of synchronous skin cancers in a patient may be managed with extensive removal in one session or limited removal in several sessions. Our objective was to prospectively evaluate the experiences of patients undergoing excisional surgery for multiple nonmelanoma skin cancers in one session. Patients scheduled for excision of five or more skin lesions in one operative session were prospectively surveyed and followed for outcomes. Patients were surveyed immediately postoperatively and 7 and 90 days postoperatively. Ten patients were prospectively enrolled. They had a previous history of numerous skin cancers (median 76; range 4-551). The median number of lesions excised was 8 (range 5-21). All patients received local anesthesia, 90% received sedation, and none had general anesthesia. The median duration of the procedure was 480 minutes. Nine patients tolerated the procedure well. Two patients were electively hospitalized for observation because of the extent of surgery. Nine patients were very satisfied with the megasession. Carefully selected patients with extensive skin cancer can tolerate excisional surgery of a large number of cutaneous neoplasms in one session, with few and readily managed complications. Most of our patients preferred extensive tumor removal in one session to removal of fewer tumors in several sessions.


Recording of Brugada electrocardiogram pattern by an implantable cardiac monitor.
A 51-year-old man with Brugada syndrome (BrS) electrocardiogram (ECG) type I pattern underwent implantable cardiac monitor (ICM) insertion. After pre-insertion potential mapping, we could observe the patient-specific repolarization abnormalities on the subcutaneous ECG provided by the ICM. A few weeks later, we received remotely a device recording with a higher ST-segment elevation and a longer duration of the interval between the onset of the coved elevation and its termination at the isoelectric line. Our observation supports the conceptual premise that ICM could add information on quantifying the amount of time with abnormal ECG patterns rather than only for the diagnosis of cardiac arrhythmias.


Urothelial Carcinoma: Divergent Differentiation and Morphologic Subtypes.
Urothelial carcinoma (UC) is known to encompass a wide spectrum of morphologic features and molecular alterations. Approximately 15% to 25% of invasive UC exhibits histomorphologic features in the form of "divergent differentiation" along other epithelial lineages, or different "subtypes" of urothelial or sarcomatoid differentiation. It is recommended that the percentage of divergent differentiation and or subtype(s) be reported whenever possible. Recent advances in molecular biology have led to a better understanding of the molecular underpinning of these morphologic variations. In this review, we highlight histologic characteristics of the divergent differentiation and subtypes recognized by the latest version of WHO classification, with updates on their molecular and clinical features.


Field evaporation and atom probe tomography of pure water tips.
Measuring biological samples by atom probe tomography (APT) in their natural environment, i.e. aqueous solution, would take this analytical method, which is currently well established for metals, semi-conductive materials and non-metals, to a new level. It would give information about the 3D chemical structure of biological systems, which could enable unprecedented insights into biological systems and processes, such as virus protein interactions. For this future aim, we present as a first essential step the APT analysis of pure water (Milli-Q) which is the main component of biological systems. After Cryo-preparation, nanometric water tips are field evaporated with assistance by short laser pulses. The obtained data sets of several tens of millions of atoms reveal a complex evaporation behavior. Understanding the field evaporation process of water is fundamental for the measurement of more complex biological systems. For the identification of the individual signals in the mass spectrum, DFT calculations were performed to prove the stability of the detected molecules.


[Herpetic meningoencephalitis in infants. Study of 7 cases].
Seven children with herpes meningoencephalitis aged between 14 days and 13 months were studied. The herpes infection was confirmed by isolation of herpes virus from the CSF (one case), from the brain (one case), and in the 5 remaining cases by serology. The strains isolated were herpes type 2. The clinical features of herpes meningoencephalitis in the first year of life and the laboratory data are described.


[Equipment for lyoluminescent dosimetry].
The paper deals with experience gained during construction of photometry set suitable for application in lyoluminiscent dosimetry. Results of stability measurement are presented and possibilities of constructing these apparatuses using Czechoslovak parts are discussed.


[Endoscopic vacuum therapy for Boerhaave's syndrome].
Operative and interventional treatment of Boerhaave's syndrome include closure of the esophageal defect and drainage of the septic focus. Initial reports on the use of endoscopic vacuum therapy (EVT) of Boerhaave's syndrome are now available. This article describes the experiences gained from the clinical application in two patients using this new surgical endoscopic procedure. The current literature regarding treatment of Boerhaave's syndrome is presented. Open-pore drainage is endoscopically placed either through the transmural defect in the extraluminal wound cavity (intracavitary EVT) or overlapping the defect into the esophageal lumen (intraluminal EVT). The application of a negative pressure results in active drainage directed to the lumen and simultaneously in defect closure. Through these therapeutic measures the perforation defect and the septic focus can be healed. Open-pore drains are manufactured from drainage tubes and open-pore foam or an open-pore film. In both patients the distal esophageal perforation defects were completely healed using EVT. In 1 patient the treatment with EVT alone lasted 8 days. For the second patient EVT was combined with an open thoracotomy for decortication of pleural empyema. The treatment with EVT lasted 23 days and 1 cycle of EVT was carried out with an new open-pore film drainage (OFD). Surgical treatment to close the defect or an esophageal resection was not necessary for both patients. In the currently available studies and single case reports of ETV for Boerhaave's syndrome, 11 patients (84 %) of a total of 13 patients have been successfully treated. First clinical experiences have demonstrated that with EVT draining of the septic focus and closure of the Boerhaave defect at the gastroesophageal junction can be achieved. The EVT is an organ-preserving endoscopic surgical treatment, which can be an alternative and complementary to traditional surgery.


Uptake of Oral Anticoagulants for Stroke Prevention in Patients with Atrial Fibrillation in a Single Clinical Commissioning Group in England Without Restrictions to Their Use.
In England, the uptake of direct oral anticoagulants (DOACs) for stroke prevention in atrial fibrillation has been slow and varied across different Clinical Commissioning Groups (CCGs). This study aimed to profile the prescribing of oral anticoagulants for stroke prevention in patients with atrial fibrillation over 3 years in a CCG without restrictions to DOACs use to understand more about organisational and/or individual barriers to the early uptake of DOACs. Data were collected from nine general practices between 1 April 2012 and 31 March 2015 of patients who were initiated on the oral anticoagulant therapy. Data were analysed descriptively and with independent Student's t test and Chi square test to explore if there was an association between type of oral anticoagulant initiated and sex, age, type of prescriber and prior aspirin use. The early uptake of DOACs significantly increased over the study period (p < 0.0001; medium size effect φc = 0.372). There was no statistically significant difference between sex or age and type of oral anticoagulant initiated. Primary-care prescribers were responsible for initiating the majority of oral anticoagulants (71%; N = 257) and driving the use of DOACs (72%, N = 71). Patients switched from aspirin to an oral anticoagulant were more likely to be initiated on warfarin than a DOAC. The early use of DOACs, in a CCG without restrictions to their use, was embraced by primary-care prescribers in this particular CCG.


Severe neurologic and hepatic toxicity in a newborn prenatally exposed to methamphetamine. A case report.
In the recent years the increase of methamphetamines (MTA) abusers women has become an emerging problem. Very little data has been published regarding the effects of prenatal MTA exposure. We describe a case of MTA related toxicity in a term newborn which have early onset of neonatal encephalopathy and liver failure. A term infant born to a MTA abuser mother developed seizures and severe neurological symptoms shortly after birth. Methamphetamine was detected both in maternal and in neonatal urine. The laboratoristic tests revealed severe hepatic insufficiency, coagulopathy and thrombocytopenia. Due to neonatal encephalopathy the newborn underwent hypothermia. Phenobarbital, fresh frozen plasma, platelet transfusions and vitamin K were administered. Cranial ultrasonography and magnetic resonance imaging (MRI) showed diffuse white matter damage and two ischemic-hemorrhagic cerebral lesions. Gradually the clinical conditions improved, at 1 month MRI showed a stabilization of cerebral lesions with residual diffuse leukomalacia. Physiotherapy and neurological follow up is ongoing to evaluate the long term effects. although infrequent, MTA-related toxicity should be suspected in infants with neurologic and hepatic symptoms. Further studies are warranted to confirm our findings in order to identify newborns at high risk of acute MTA toxicity in time to provide them the appropriate support.


Molecular heterozygosity and genetic exploitations of Trichoderma inter-fusants enhancing tolerance to fungicides and mycoparasitism against Sclerotium rolfsii Sacc.
Protoplast fusion is an imperative tool to develop Trichoderma inter-fusants having desire traits through genetic manipulation. Study designed to develop diverse Trichoderma fusants for fungicide tolerance (Mancozeb, Thiram, Tebuconazole, and Carbendazim) and enhanced mycoparasitic activity against Sclerotium rolfsii sacc. The mycoparasitic T. virens NBAII Tvs12 and fungicide tolerant T. koningii MTCC 796 were utilized for protoplast fusion. The derived inter-fusants were subjected to diploidization using d-camphor in minimal media followed by successive three sub culturing onto potato dextrose agar to obtain 36 stable fusants. The stable fusants were employed for conidial size, fungicide tolerance, mycoparasitism, gene specific SSR amplification and molecular heterozygosity analysis. The results explained that 22 homozygous mutants illustrated characteristic of either one parental strain and 14 heterozygous recombinants depicted traits of both parental strains. The antagonistic activity of fusants against S. rolfsii depicted highest growth inhibition (87.91%) by potent inter-fusant (Fu 21) with improved fungicide tolerance capacity. The molecular study revealed highest observed heterozygocity (0.544), coefficient of gene differentiation (0.526) and gene flow (0.387) by Fu 21 indicating better genetic exploitation of parental strains into that fusant with good genetic purity. Principal coordinate analysis of fusants and parental strains exhibited 65.07% total variation and confirmed the scattering pattern matched with UPGMA clustering pattern. The stable heterozygous Fu 21 derived from inter-fusion between Tvs 12 and MTCC 796 might be useful to practice eco-friendly bioformulation tolerance to fungicides for effective integrated stem rot disease management in groundnut.


Design and fabrication of a GaN HEMT power amplifier based on hidden Markov model for wireless applications.
Improvement of power amplifier's performance is the desired topic in communication systems. There are many efforts are made to provide good input and output matching, high efficiency, sufficient power gain and appropriate output power. This paper presents a power amplifier with optimized input and output matching networks. In the proposed approach, a new structure of the Hidden Markov Model with 20 hidden states is used for modeling the power amplifier. The widths and lengths of the microstrip lines in the input and output matching networks are defined as the parameters that the Hidden Markov Model should optimize. For validating our algorithm, a power amplifier has been realized based on a 10W GaN HEMT with part number CG2H40010F from the Cree corporation. Measurement results have shown a PAE higher than 50%, a Gain of about 14 dB, and input and output return losses lower than -10 dB over the frequency range of 1.8-2.5 GHz. The proposed PA can be used in wireless applications such as radar systems.


[Pilot study evaluating the ratio of adverse drug reactions related to antimicrobials over their consumption in 2012-2013].
As part of our antimicrobials stewardship program, we were interested in the use of antimicrobials and prevalence of adverse drug reactions associated with the use of these drugs. The retrospective and descriptive study was conducted over a one year-period between April 1st 2012 and March 31st 2013 in a mother-child Hospital. We determined the ratio: number of adverse drug reactions over 10,000 defined daily dose or 10,000days of therapy. We identified the ratios higher than average for which the confidence interval did not cross the calculated average. The severity of the adverse drug reactions was codified using the Common Terminology Criteria for Adverse Events. We found 570 adverse drug reactions including 100 (17.5%) adverse drug reactions related to antimicrobials during the financial year 2012-2013. It represented 96 patients. Thus, five antimicrobials, for which the confidence interval does not cross the calculated average value, may be targeted in risk management because they have a higher ratio than average: piperacillin (290 [113-722]), valganciclovir (244 [43-1260]), ceftriaxone (114 [56-234]), acyclovir (76 [26-220]) and liposomal amphotericin B (72 [20-258]). In a mother-child university hospital, we calculated a ratios of 19 [15-23] and 13 [10-15], it allows us targeting some antimicrobials in our approach to prevention and management of adverse drug reactions.


Exploring molecular networks directly in the cell.
The hierarchy of cell function comprises at least four distinct functional levels: genome, transcriptome, proteome, and toponome. The toponome is the entirety of all protein networks traced out directly as patterns on the single cell level in the natural environment of cells in situ (e.g. tissues). In this work a photonic microscopic robot technology (MELK) capable of tagging and imaging hundreds (and possibly thousands) of different molecular components (e.g. proteins) of morphologically-intact fixed cells and tissue have been developed. MELK data sets represent multidimensional vectors of the topologically determined arrangements of proteins within the cell. The data, assembled in a toponome dictionary of the cell, give rise to a new concept for target and drug lead discovery.


Attributes and risk factors of positive margins on 864 excisions of basal cell carcinomas: a single-center retrospective study.
Background: Residual tumors increase the likelihood of recurrence of basal cell carcinoma (BCC).Objective: We determined the attributes and risk factors for positive surgical margins (+SM) of excised BCC in a university hospital.Methods: In this cross-sectional retrospective study, we reviewed the histologic reports of BCC removed via conventional surgical excision (CSE) by specialists from different fields.Results: Among excised BCCs (n = 864), there was a predominance of nodular BCC (82.64%) in the facial H-area (72.81%; average diameter = 9.12 mm), which had the highest + SM rate (20.17%). Most cephalic (ce-BCC; 69.01%) and non-cephalic (91.11%) BCCs were excised by dermatologists, with low rates of + SM (4.53%; 1.46%, respectively); the overall + SM rate was 12.73%. Men had larger (p < .001) and more ulcerated (p = .04) BCC. An aggressive histologic pattern (Ag-P) (p < .04) and ulceration (p < .001) were correlated with tumor size on multivariate analysis. The risk for + SM increased in ulcerated ce-BCC (p = .02), BCC with Ag-P (p = .02), and in the H-area (p < .001), nasal (p = .007), and labial (p = .05) regions. ce-BCC excised by head-neck surgeons had a high chance of ulceration (p < .001) and Ag-P (p = .002).Conclusions: Ag-P and H-zone remain critical risk factors for + SM. Accordingly appropriate treatment protocols should be used to ensure low + SM rates via CSE.


A computational model of a network of initial lymphatics and pre-collectors with permeable interstitium.
Initial lymphatic vessels are made up of overlapped endothelial cells that act as unidirectional valves enabling one-way drainage of tissue fluid into the lumen of the initial lymphatics when there is a favourable pressure gradient. Initial lymphatics subsequently drain this fluid into the collecting lymphatics. This paper describes a computational model for a network of passive rat mesenteric lymphatic vessels with sparse secondary valves. The network was simulated with the secondary valves both operational and non-operational. The effects on the cycle-mean outflow-rate from the network of both inflammation and the resistance of the surrounding interstitium were considered. The cycle-mean outflow-rate is sensitive to vessel stiffness. If the influence of primary-valve resistance is reduced relative to that of interstitial resistance and intravascular resistance, there is no absolute advantage of extrinsic pumping, since maximum outflow-rate occurs when vessels are rigid. However, there is relative advantage, in that the outflow-rate at intermediate stiffness is higher with the secondary valves functioning than when they are deactivated. If primary-valve resistance dominates, then extrinsic pumping of non-rigid vessels provides absolute advantage. The nonlinear relation between pressure drop and flow-rate of the endothelial primary valves, combined with downstream compliance and pulsatile external pressure, constitutes a separate mechanism of pumping. By enabling the consideration of interactions between multiple phenomena (primary valves, secondary valves, a real network geometry with multiple branches, deformable vessel walls, interstitial resistance and external pressures), the model offers a perspective for delineating physiological phenomena that have not yet been fully linked to the biomechanics of fluid flow through initial lymphatic networks.


Surge capacity for critical care specialised allied health professionals in Australia during COVID-19.
Significant investment in planning and training has occurred across the Australian healthcare sector in response to the COVID-19 pandemic, with a primary focus on the medical and nursing workforce. We provide a short summary of a recently published article titled "Surge capacity of Australian intensive care units associated with COVID-19 admissions" in the Medical Journal of Australia and, importantly, highlight a knowledge gap regarding critical care specialised allied health professional (AHP) workforce planning in Australia. The unique skill set provided by critical care specialised AHPs contributes to patient recovery long after the patient leaves the intensive care unit, with management targeted at reducing disability and improving function, activities of daily living, and quality of life. Allied health workforce planning and preparation during COVID-19 must be considered when planning comprehensive and evidence-based patient care. The work by Litton et al. has highlighted the significant lack of available data in relation to staffing of critical care specialised AHPs in Australia, and this needs to be urgently addressed.


Development of mercury (II) ion biosensors based on mercury-specific oligonucleotide probes.
Mercury (II) ion (Hg(2+)) contamination can be accumulated along the food chain and cause serious threat to the public health. Plenty of research effort thus has been devoted to the development of fast, sensitive and selective biosensors for monitoring Hg(2+). Thymine was demonstrated to specifically combine with Hg(2+) and form a thymine-Hg(2+)-thymine (T-Hg(2+)-T) structure, with binding constant even higher than T-A Watson-Crick pair in DNA duplex. Recently, various novel Hg(2+) biosensors have been developed based on T-rich Mercury-Specific Oligonucleotide (MSO) probes, and exhibited advanced selectivity and excellent sensitivity for Hg(2+) detection. In this review, we explained recent development of MSO-based Hg(2+) biosensors mainly in 3 groups: fluorescent biosensors, colorimetric biosensors and electrochemical biosensors.


Management of delayed arterial hemorrhage after pancreaticoduodenectomy. A case series.
CONTEXT Delayed arterial hemorrhage is a rare complication after pancreaticoduodenectomy (frequency 2-4%) but carries a high mortality, with up to a third of patients dying as a consequence. Its ideal management remains unclear. Between 1993 and 2007, 317 head of pancreas resections were performed at our institution; there were 5 cases of delayed arterial hemorrhage (frequency 1.6%). This paper presents our experience in the management of delayed arterial haemorrhage post pancreaticoduodenecomy and discusses the role of angiograms, endoscopy and laparotomy in its management.


Y chromosome loss in cancer drives growth by evasion of adaptive immunity.
Loss of the Y chromosome (LOY) is observed in multiple cancer types, including 10-40% of bladder cancers1-6, but its clinical and biological significance is unknown. Here, using genomic and transcriptomic studies, we report that LOY correlates with poor prognoses in patients with bladder cancer. We performed in-depth studies of naturally occurring LOY mutant bladder cancer cells as well as those with targeted deletion of Y chromosome by CRISPR-Cas9. Y-positive (Y+) and Y-negative (Y-) tumours grew similarly in vitro, whereas Y- tumours were more aggressive than Y+ tumours in immune-competent hosts in a T cell-dependent manner. High-dimensional flow cytometric analyses demonstrated that Y- tumours promote striking dysfunction or exhaustion of CD8+ T cells in the tumour microenvironment. These findings were validated using single-nuclei RNA sequencing and spatial proteomic evaluation of human bladder cancers. Of note, compared with Y+ tumours, Y- tumours exhibited an increased response to anti-PD-1 immune checkpoint blockade therapy in both mice and patients with cancer. Together, these results demonstrate that cancer cells with LOY mutations alter T cell function, promoting T cell exhaustion and sensitizing them to PD-1-targeted immunotherapy. This work provides insights into the basic biology of LOY mutation and potential biomarkers for improving cancer immunotherapy.