Effect of two herbicides on Xenylla welchi (Hexapoda:Collembola) under laboratory conditions.
Xenylla welchi was used to evaluate toxicity of two herbicide formulations, pretilachlor (50 EC) and pendimethalin (30 EC) under laboratory conditions. Twenty four hours LC₅₀ value of pretilachlor and pendimethalin formulations on Xenylla welchi were 72.7 and 190.0 g a.i/ha respectively which were less than their corresponding recommended agricultural doses. Again pretilachlor attained fastest LT₅₀ (110 min) followed by pendimethalin (140 min). Significant reductions in hatching success were noted with the application of both the herbicide formulations at all doses excepting ¹/₈ and ¹/₁₀th of LC₅₀ (9.1, 7.3 and 23.8, 19.0 g a.i/ha for pretilachlor and pendimethalin, respectively). Hatching success of the test specimens recorded 44.1 and 63.3% reduction from control for the highest applied dose (½ of LC₅₀) of pretilachlor and pendimethalin, respectively. Juveniles of Xenylla welchi exposed to ¹/₆, ¹/₈ and ¹/₁₀th LC₅₀ for pretilachlor (12.1, 9.1, 7.3 g a.i/ha) and ¹/₈ and ¹/₁₀th LC₅₀ for pendimethalin (23.8, 19.0 g ai/ha) survived and exhibited increased moulting frequency (7 moultings in 28 days in both the herbicide treatments) in comparison to control (8 moulting in 42 days). Test specimens required 26.0 ± 1.2 and 28.1 ± 2.1 days to attain sexual maturity exposed to pretilachlor and pendamethalin respectively which was significantly less than control (42 ± 2.6 days).


Stress-Reducing Effect of a 50 Hz Electric Field in Mice after Repeated Immobilizations, Electric Field Shields, and Polarization of the Electrodes.
In BALB/c mice, immobilization-increased plasma glucocorticoid (GC) levels are suppressed by extremely low frequency (ELF) electric fields (EF). The aim of this study was to advance our understanding of the biological effects of ELF-EF, using its suppressive effect on the GC response. Mice were exposed to a 50 Hz EF of 10 kV/m via a parallel plate electrode and immobilized as needed. We examined the suppressive effect of ELF-EF on GC level change after repeated immobilizations, electrode polarization, and EF shielding of different portions of the mouse body parts. Additionally, bodyweight changes owing to stress and EF were examined. Immobilization-induced reduction in the plasma GC levels was reproduced in mice with stress and EF exposure, regardless of the stress episode numbers and electrode polarization. Furthermore, when the head of mice was shielded from the EF, the suppressive effect was possibly relatively lower than that when the abdomen was shielded. The bodyweight of the mice decreased for 3 days after immobilization before recovering; ELF-EF did not affect the bodyweight. Thus, to elicit the biological effects of the EF, not only the size of the area where the EF is distributed but also the area where the field is distributed should be important. The results also confirmed the stableness of the present experimental system, at least in terms of the stress-reducing effect. In addition, the restriction in this study caused weight loss, but ELF-EF was not considered to affect it. The results improve the understanding of the biological effect and medical applications of ELF-EF.


Chromosome analyses in a rhabdoid tumor of the brain.
A malignant rhabdoid tumor of the brain from a 19-month-old child was studied. Two related clones, 46,XX,-8,+der(8)t(8;22)(p11;q?12)x2,-22,del(22)(q12q?13) and 46,XX-8,+der(8)t(8;22) (p11;q?12) x2,-22,r(22) were found after chromosome analyses of primary and recurrent tumor, and multiple nude mouse passages of the tumor. Breakpoints were studied using FISH.


Structure-guided affinity maturation of a single-chain variable fragment antibody against the Fu-bc epitope of the dengue virus envelope protein.
Dengue is one of the most dominant arthropod-borne viral diseases, infecting at least 390 million people every year throughout the world. Despite this, there is no effective treatment against dengue, and the only available vaccine has already been withdrawn owing to the significant adverse effects. Therefore, passive immunotherapy using monoclonal antibodies is now being sought as a therapeutic option. To date, many dengue monoclonal antibodies have been identified, most of which are serotype-specific, and only a few of which are cross-reactive. Furthermore, antibodies that cross-react within serotypes are weakly neutralizing and frequently induce antibody-dependent enhancement, which promotes viral entry and replication. Therefore, broadly neutralizing antibodies with no risk of antibody-dependent enhancement are required for the treatment of dengue. Here, we developed a single-chain variable fragment (scFv) antibody from an anti-fusion loop E53 antibody (PDB: 2IGF). We introduced previously predicted favorable complementarity-determining region (CDR) mutations into the gene encoding the scFv antibody for affinity maturation, and the resultant variants were tested in vitro against the highly conserved fusion and bc epitope of the dengue virus envelope protein. We show some of these scFv variants with two to three substitution mutations in three different CDRs possess affinity constants (KD) ranging from 20 to 200 nM. The scFv-mutant15, containing D31L, Y105W, and S227W substitutions, showed the lowest affinity constant, (KD = 24 ± 7 nM), approximately 100-fold lower than its parental construct. We propose that the scFv-derivative antibody may be a good candidate for the development of an effective and safe immunotherapy.


The role of peroxisome proliferator-activated receptor gamma coactivator-1 beta in the pathogenesis of fructose-induced insulin resistance.
Peroxisome proliferator-activated receptor gamma coactivator-1 beta (PGC-1beta) is known to be a transcriptional coactivator for SREBP-1, the master regulator of hepatic lipogenesis. Here, we evaluated the role of PGC-1beta in the pathogenesis of fructose-induced insulin resistance by using an antisense oligonucletoide (ASO) to knockdown PGC-1beta in liver and adipose tissue. PGC-1beta ASO improved the metabolic phenotype induced by fructose feeding by reducing expression of SREBP-1 and downstream lipogenic genes in liver. PGC-1beta ASO also reversed hepatic insulin resistance induced by fructose in both basal and insulin-stimulated states. Furthermore, PGC-1beta ASO increased insulin-stimulated whole-body glucose disposal due to a threefold increase in glucose uptake in white adipose tissue. These data support an important role for PGC-1beta in the pathogenesis of fructose-induced insulin resistance and suggest that PGC-1beta inhibition may be a therapeutic target for treatment of NAFLD, hypertriglyceridemia, and insulin resistance associated with increased de novo lipogenesis.


Immunoreactive prolactin like material in the urine of women.
Immunoreactive prolactin-like material (Ir Prl) was detected in urines of eugonadal women during the luteal phase and in urines of pregnant and lactating women. The levels of Ir Prl urinary excretion per 24 h and of elimination per 100 ml of glomerular filtrate were highest in lactating women as compared to pregnant women; levels in pregnant women were elevated as compared to eugonadal subjects. Iv injection of thyrotropin releasing hormone (TRH, 200 micrograms) caused increased levels of urinary Ir Prl. The physiochemical characteristics of urinary Ir Prl of lactating women were investigated by filtrating urine samples on Ultragel Aca 54 in presence or absence of Trasylol. Urines, supplemented with Trasylol and analyzed either immediately or after storage at room temperature for 24 h, contained in addition to the 23,000 Mr monomeric form (25.2 +/- 7.4%), two fractions of high (greater than or equal to 70,000) or low (less than 23,000) molecular weight, respectively. The latter material largely predominated (73.5 +/- 7.3%). Urines kept at room temperature for 24 h without Trasylol showed variable but significant decreases in the monomer form with a parallel increase in high MW and fragmented forms. The extent of degradation of the monomer was directly proportional to the proteolytic activity of the urines as estimated by the Azocoll breakdown test. Contrary to what was observed with the urinary endogenous monomeric Prl, human pituitary Prl remained unaltered upon incubation in Trasylol-free urines up to 45 h.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of dietary protein on glomerular renin secretion.
Previous studies from our and other laboratories demonstrated that dietary protein restriction lowers plasma renin activity by impairing renin release. The effect of protein intake on glomerular renin secretion has not been investigated. Accordingly, we studied male Sprague-Dawley rats weighing 180 to 200 g for 3 weeks that were receiving isocaloric diets that provided either standard 20% protein (SP) or low 6% protein (LP). Renin secretion was measured in the glomeruli isolated from these rats, at baseline and following stimulation with arachidonic acid and isoproterenol. The activity of plasma renin (3.0 +/- 0.5 ng/mL/min on SP v 1.1 +/- 0.1 ng/mL/min on LP) was significantly (P < 0.02) lower on LP intake. In contrast, glomerular renin content (22.9 +/- 0.7 ng/micrograms protein on SP v 32.3 +/- 1.4 ng/micrograms protein on LP) was significantly (P < 0.01) higher on the LP diet. Furthermore, renin secretion (ng/mL/h) from the isolated glomeruli at baseline (3.9 +/- 1.0 on SP v 12.5 +/- 3.0 on LP, P < 0.02), and following incubation with arachidonic acid 10(-5) mol/L (5.9 +/- 1.7 on SP v 19.6 +/- 3.1 on LP, P < 0.005), and isoproterenol 10(-3) mol/L (6.0 +/- 0.5 on SP v 17.3 +/- 3.3 on LP, P < 0.01) was significantly higher on the LP diet. These studies suggest that dietary protein restriction impairs in vivo renin release. In contrast, in vitro glomerular renin release is augmented by protein restriction. The factors modulating in vivo renin release require further characterization.


Pharmacokinetic Similarity of ABP 710, a Proposed Biosimilar to Infliximab: Results From a Randomized, Single-Blind, Single-Dose, Parallel-Group Study in Healthy Subjects.
This was a randomized, single-blind, single-dose, 3-arm parallel-group study. Healthy subjects were randomized to receive ABP 710 (n = 50) or infliximab reference product (RP) sourced from the United States (infliximab US; n = 50) or the European Union (infliximab EU; n = 50) 5 mg/kg intravenously over 2 hours. The primary endpoint was area under the serum concentration-time curve from time 0 extrapolated to infinity (AUCinf ) for the comparison of ABP 710 to infliximab US and infliximab EU. Secondary endpoints included safety, tolerability, and immunogenicity. AUCinf was similar across the 3 groups, showing similarity of ABP 710 to infliximab RP as well as similarity of infliximab US with infliximab EU. Geometric mean ratio of AUCinf was 0.89 between ABP 710 and infliximab US, 1.00 between ABP 710 and infliximab EU, and 1.11 between infliximab US and infliximab EU. All 90% confidence intervals of the geometric mean ratios were fully contained within the prespecified standard pharmacokinetic equivalence criteria range of 0.80 to 1.25. Treatment-related adverse events were mild to moderate and reported for 83.7%, 86.0%, and 83.7% of subjects in the ABP 710, infliximab US, and infliximab EU treatment groups, respectively; incidence of antidrug antibody rates observed across the 3 groups were similar. Results of this study demonstrated pharmacokinetic similarity of ABP 710 with infliximab RP following a single 5-mg/kg intravenous injection. The safety and tolerability of ABP 710 and infliximab RP were comparable. These results add to the totality of evidence providing further support that the proposed biosimilar ABP 710 is similar to infliximab RP. (Trial ID: ACTRN12614000903684.).


Linc-ROR targets FGF2 to regulate HASMC proliferation and migration via sponging miR-195-5p.
Atherosclerosis is a common cardiovascular disorder and is characterized by damage of endothelial cells, cell inflammation, hyper-proliferation of vascular smooth muscle cells and the accumulation of extracellular lipids and fibrous tissues. In this study, we firstly examined the expression level of long intergenic non-protein coding RNA, regulator of reprogramming (linc-ROR) in homocysteine (Hcy)-stimulated human aortic smooth muscle cells (HASMCs), and then looked into the potential molecular signaling axis of linc-ROR in regulating the proliferation and migration of HASMCs. Hcy promoted HASMC proliferation and up-regulated linc-ROR expression. Functional studies showed that linc-ROR exerted enhanced actions on the proliferation and migration of HASMCs. In addition, linc-ROR acted as a competing endogenous RNA for miR-195-5p and repressed the miR-195-5p expression in HASMCs. Linc-ROR was up-regulated the miR-195-3p was down-regulated in the plasma from CAD patients when compared to normal controls. Furthermore, fibroblast growth factor 2 (FGF2) was identified as a target of miR-195-5p and was negatively regulated by miR-195-5p in HASMCs. The rescue experiments revealed that linc-ROR-mediated HASMC proliferation and migration may be via regulating miR-195-5p/FGF2 axis. Linc-ROR inhibition blocked the miR-195-5p/FGF2 signaling in Hcy-treated HASMCs, and this effect may also involve in the miR-195-5p/FGF2 axis. To summarize, the data of the present study identified the up-regulation of linc-ROR in Hcy-stimulated HASMCs, and further mechanistic functional studies revealed that linc-ROR promoted HASMC proliferation and migration via regulating miR-195-5p/FGF2 axis. The present study provided the novel actions of linc-ROR in regulating HASMC proliferation and migration, which may be related to the pathophysiology of atherosclerosis.


Variations in dose distributions by the use of independent asymmetric jaws. A new technique for irradiation of localized carcinoma of the prostate.
The use of independent jaws set asymmetrically in the moving field technique with bilateral arcs allows the entirely new dose distributions be obtained. The basic principle of this technique is that, with the use of moving field technique with bilateral arcs, the independent jaw more proximate to the central ray (axis) of beam must always be on the side of the critical organ. In this area the characteristic deformation of isodoses and the formation of very steep dose slope occur. We consider as optimum technique for the target irradiation of the prostatic carcinoma the moving field technique with bilateral 105 degrees arcs with 20 MeV X-ray beam of linear accelerator and with independent jaws set asymmetrically, when the independent jaw more proximate to the central ray is always + 1.5 cm from the central ray of the beam.


Analysis of procarbazine and metabolites by gas chromatography-mass spectrometry.
Twelve compounds representing procarbazine, seven metabolites, and an internal standard were analyzed by gas chromatography-mass spectrometry on a 3% OV-1 column. Procarbazine and four metabolites were derivatized with acetic anhydride. A sensitive, specific and quantitative assay was established by selected ion monitoring using a synthetic analogue of the drug as an internal standard. The limits of detection were approximately 1 ng/ml of plasma while the limits of quantitation were 10 ng/ml of plasma. Studies of the degradation of procarbazine . HCl in 0.05 M phosphate buffer (pH 7.4) were compared to in vivo studies. At 1 h after incubation of procarbazine . HCl in buffer, the azo and aldehyde metabolites were detected in the highest concentrations representing 27.2% and 20.3% of total drug and metabolites. In the in vivo studies, analyses of rat plasmas indicated that 1 h after an oral dose of procarbazine . HCl, the aldehyde metabolite represented 72% of the total drug and metabolites, and that relatively little of the azo metabolite was present.


Oxytocinergic circuit from paraventricular and supraoptic nuclei to arcuate POMC neurons in hypothalamus.
Intracerebroventricular injection of oxytocin (Oxt), a neuropeptide produced in hypothalamic paraventricular (PVN) and supraoptic nuclei (SON), melanocortin-dependently suppresses feeding. However, the underlying neuronal pathway is unclear. This study aimed to determine whether Oxt regulates propiomelanocortin (POMC) neurons in the arcuate nucleus (ARC) of the hypothalamus. Intra-ARC injection of Oxt decreased food intake. Oxt increased cytosolic Ca(2+) in POMC neurons isolated from ARC. ARC POMC neurons expressed Oxt receptors and were contacted by Oxt terminals. Retrograde tracer study revealed the projection of PVN and SON Oxt neurons to ARC. These results demonstrate the novel oxytocinergic signaling from PVN/SON to ARC POMC, possibly regulating feeding.


Listening loops and the adapting auditory brain.
Analysing complex auditory scenes depends in part on learning the long-term statistical structure of sounds comprising those scenes. One way in which the listening brain achieves this is by analysing the statistical structure of acoustic environments over multiple time courses and separating background from foreground sounds. A critical component of this statistical learning in the auditory brain is the interplay between feedforward and feedback pathways-"listening loops"-connecting the inner ear to higher cortical regions and back. These loops are likely important in setting and adjusting the different cadences over which learned listening occurs through adaptive processes that tailor neural responses to sound environments that unfold over seconds, days, development, and the life-course. Here, we posit that exploring listening loops at different scales of investigation-from in vivo recording to human assessment-their role in detecting different timescales of regularity, and the consequences this has for background detection, will reveal the fundamental processes that transform hearing into the essential task of listening.


Identification of a Nomogram with an Autophagy-Related Risk Signature for Survival Prediction in Patients with Glioma.
Glioma is a common type of tumor in the central nervous system characterized by high morbidity and mortality. Autophagy plays vital roles in the development and progression of glioma, and is involved in both normal physiological and various pathophysiological progresses. A total of 531 autophagy-related genes (ARGs) were obtained and 1738 glioma patients were collected from three public databases. We performed least absolute shrinkage and selection operator regression to identify the optimal prognosis-related genes and constructed an autophagy-related risk signature. The performance of the signature was validated by receiver operating characteristic analysis, survival analysis, clinic correlation analysis, and Cox regression. A nomogram model was established by using multivariate Cox regression analysis. Schoenfeld's global and individual test were used to estimate time-varying covariance for the assumption of the Cox proportional hazard regression analysis. The R programming language was used as the main data analysis and visualizing tool. An overall survival-related risk signature consisting of 15 ARGs was constructed and significantly stratified glioma patients into high- and low-risk groups (P < 0.0001). The area under the ROC curve of 1-, 3-, 5-year survival was 0.890, 0.923, and 0.889, respectively. Univariate and multivariate Cox analyses indicated that the risk signature was a satisfactory independent prognostic factor. Moreover, a nomogram model integrating risk signature with clinical information for predicting survival rates of patients with glioma was constructed (C-index=0.861±0.024). This study constructed a novel and reliable ARG-related risk signature, which was verified as a satisfactory prognostic marker. The nomogram model could provide a reference for individually predicting the prognosis for each patient with glioma and promoting the selection of optimal treatment.


Position of targets and period of competence for UV-induction of the malformation "Double Abdomen" in the egg ofSmittia spec. (Diptera, Chironomidae).
1. UV irradiation of anterior pole regions of eggs ofSmittia results in the formation of "double abdomens". The frequency of this malformation has been recorded as a function of developmental stage, size and position of irradiated area, and UV dose. 2. The efficiency of irradiation decreases with increasing longitudinal extent of the irradiated anterior area. 3. Within the anterior fourth of the egg, irradiation of peripheral regions is more effective than irradiation of central regions. 4. The varying efficiency of irradiation is thought to represent a corresponding distribution in the concentration of effective targets or the morphogenetic efficiency of the targets in the irradiated state. Alternative interpretations are discussed. 5. There is a multiplicity of targets distributed symmetrically to the longitudinal egg axis. 6. The effective targets have been proved to be localized in the ooplasm of eggs aged less than 1 h. There is evidence to show that the targets are confined to the ooplasm during all stages studied. 7. The targets are probably stored during oogenesis. 8. The irradiated targets affect the body segment pattern far beyond the irradiated area. 9. Possible relations between the targets for UV-induction of double abdomens and factors that are involved in the formation of the normal body segment pattern are discussed.


Effectiveness of call system implementation for postpartum hemorrhage in a tertiary emergency medical center: a retrospective cohort study.
Postpartum hemorrhage is the leading cause of maternal death and severe maternal morbidity worldwide. Previous studies have reported the importance of multidisciplinary treatment approaches for postpartum hemorrhage; however, only a few studies have shown a clear improvement in maternal outcomes. Therefore, this study aimed to investigate the efficacy of a call system for postpartum hemorrhage in a tertiary emergency facility for rapid multidisciplinary treatment and its effect on maternal outcomes. This single-center retrospective cohort study included patients transferred to our hospital due to postpartum hemorrhage between April 1, 2013, and March 31, 2019. The primary outcome was mortality, and the secondary outcomes were morbidity (duration of hospital stay, duration of intensive care unit stay, admission to the intensive care unit, respirator use, duration of ventilator support, acute kidney injury, transfusion-associated circulatory overload/transfusion-related acute lung injury, hysterectomy, composite adverse events, blood transfusion initiation time, blood transfusion volume, and treatment for postpartum hemorrhage). An in-hospital call system implementation commenced on April 1, 2016. The study outcomes were compared 3 years before and after implementing the call system. The blood transfusion initiation time and duration of hospital stay were significantly shortened after implementing the call system for postpartum hemorrhage. No maternal deaths were observed after implementing the system. Implementing call systems specialized for postpartum hemorrhage in tertiary emergency facilities may improve maternal outcomes.


BCL9/STAT3 regulation of transcriptional enhancer networks promote DCIS progression.
The molecular processes by which some human ductal carcinoma in situ (DCIS) lesions advance to the more aggressive form, while others remain indolent, are largely unknown. Experiments utilizing a patient-derived (PDX) DCIS Mouse INtraDuctal (MIND) animal model combined with ChIP-exo and RNA sequencing revealed that the formation of protein complexes between B Cell Lymphoma-9 (BCL9), phosphoserine 727 STAT3 (PS-727-STAT3) and non-STAT3 transcription factors on chromatin enhancers lead to subsequent transcription of key drivers of DCIS malignancy. Downregulation of two such targets, integrin β3 and its associated metalloproteinase, MMP16, resulted in a significant inhibition of DCIS invasive progression. Finally, in vivo targeting of BCL9, using rosemary extract, resulted in significant inhibition of DCIS malignancy in both cell line and PDX DCIS MIND animal models. As such, our studies provide compelling evidence for future testing of rosemary extract as a chemopreventive agent in breast cancer.


Anemia and Diabetic Kidney Disease Had Joint Effect on Diabetic Retinopathy Among Patients With Type 2 Diabetes.
Whether the association between diabetic kidney disease (DKD) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) is leveraged by anemia remains unclear. This study is to evaluate the joint effect of DKD and anemia on DR. Data were collected from electronic medical records of 1389 patients with T2DM in the Yiwu Central Hospital of Zhejiang Province from 2018 to 2019. Based on retinal examination findings, patients were classified as without diabetic retinopathy (non-DR), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). Odds ratio (OR) from multinomial logistic regression models adjusting for potential risk factors of DR were used to evaluate associations of DKD, renal function measures, and anemia with risk of NPDR and PDR. Path analysis was performed to help understand the association of DKD and hemoglobin (Hb) with DR. The study included 901 patients with non-DR, 367 patients with NPDR and 121 patients with PDR. Both high DKD risk and abnormal renal function measures were significantly associated with PDR. Anemia was associated with increased risk of NPDR (OR = 1.75, 95% confidence interval [CI] = 1.18-2.58) and PDR (OR = 3.71, 95% CI = 2.23-6.18). DKD severity and anemia had joint effect on NPDR (OR = 2.29, 95% CI = 1.32-3.96) and PDR (OR = 11.31, 95% CI = 5.95-21.51). These associations were supported by path analysis. DKD severity, abnormal estimated glomerular filtration rate (eGFR), and urinary albumin/creatinine ratio (UACR) were associated with increased risk of DR in patients with T2DM, and anemia had joint effect on these associations. Improving Hb level may decrease the risk of DR in patients with T2DM.


Fast-tracking after video-assisted thoracoscopic surgery lobectomy, segmentectomy, and pneumonectomy.
In the era of cost containment, a fast-tracking protocol was developed to reduce cost and shorten the length of stay after a lobectomy. The purpose of our study was to see whether a fast-tracking protocol provided a short length of stay without compromising morbidity and mortality or leading to readmission to the hospital. The protocol was to perform lobectomies by means of video-assisted thoracoscopic surgery with no routine postoperative laboratory work or chest roentgenograms. The chest tubes were discontinued once the output was less than 300 mL in a 24-hour period and there was no air leak present. If the chest tube output was low, but there was an air leak, the patient was discharged home with a Heimlich valve. Two hundred eighty-two consecutive video-assisted thoracoscopic surgery lobectomies were performed by a single surgeon during 18 months in 158 women (56%) and 124 men (44%), with a mean age of 71.2 years. Following this protocol, the mean length of stay was 3.26 days, and the median was 3 days. Seven of 282 patients (2.5%) were discharged with a Heimlich valve. There was 1 mortality. There were no complications in 251 patients (89%). Two patients were readmitted to the hospital. No chest tubes were reinserted. Using a fast-tracking protocol, video-assisted thoracoscopic surgery lobectomy with anatomic dissection can be performed with minimal complication, a short postoperative length of stay, and reduced costs.


Endovascular repair of an actively hemorrhaging gunshot injury to the abdominal aorta.
Endovascular stents have had a limited role in the management of trauma and vascular emergencies involving active hemorrhage. We describe a patient with delayed rupture of the infrarenal aorta after intra-abdominal sepsis caused the breakdown of a primary aortic repair. A stent-graft repair was performed, as concomitant injuries did not allow anterior access to the aorta. This report describes the successful endovascular repair of an actively hemorrhaging penetrating abdominal aortic injury. Endovascular approaches to aortic injuries may be valuable in settings where a hostile abdomen precludes traditional open repair.


Noise pollution survey of a two-storey intersection station in Tehran metropolitan subway system.
According to the world population increase and demand on transportation in mega cities, modern and low-cost technologies are remarkably considered. Meanwhile, subway system, as a means to transfer a large population of people, is extremely welcomed due to its particular advantages including time and cost savings, traffic jam avoidance, and unaffected by weather. Nevertheless, despite the benefits of these technologies, such devices also have been associated with disadvantages for human. In many subway systems, noisy environments are clearly observed; therefore, workers and even the passengers are exposed to higher noise levels than permissible limit. In this research, noise measurements were performed at Imam Khomeini Station as the most crowded intersection subway station in Tehran. In this descriptive-sectional survey, the amount of noise pollution was investigated at both stories of Imam Khomeini Intersection Station. A variety of noise pollution indicators such as L(eq) 10 min were separately measured at each storey through five measurement points from 7 A.M. to 10 P.M. It was shown that the equivalent sound level range at Imam Khomeini station towards Elmo Sanat and Imam Khomeini towards Mirdamad were between 70.56-79.54 and 68.35-79.12 dB (A), respectively. It was indicated that except for the entrance stairs to the subway waiting platform and the first section of the platform on both stories, other measurement stations have the same equivalent sound levels.


Experimentally induced true hermaphroditism in genetically female fowl.
Two types of hermaphroditism were experimentally induced in genetically female fowls by grafting of embryonic testes in embryos. Of the 27 hermaphrodites observed during the 8 months after hatching, 20 possessed a right testis and a left ovary and 7 a right testis and a left ovotestis. The testes and ovotestes contained seminiferous tubules with a more or less developed germ cell complement, attaining in many cases the early spermatid stage. The interstitial tissue was poorly functional, as shown by the absence of male secondary sex characters. The ovary or ovarian part of the ovotestes possessed numerous small ovarian follicles. The female arrangement of the plumage and the absence of spurs demonstrated the secretion of oestrogens. A mechanism is proposed for explaining this partial masculinization of genetically female gonads, a phenomenon which occurs during the period of embryonic sex differentiation, and is responsible for this experimental true hermaphroditism.


JAM2: A New Culprit at the Pathophysiology of Primary Familial Brain Calcification.
Primary familial brain calcification (PFBC) is an uncommon degenerative neurological disease that can be hereditary or sporadic, and manifests equally in both sexes and at any age. Several studies initially identified variants in four different genes as the cause of the disorder, all with an autosomal dominant inheritance pattern: SLC20A2, PDGFRB, PDGFB and XPR1. However, there have been reports of the involvement of additional genes in the autosomal recessive inheritance pattern, such as MYORG and more recently JAM2, suggesting that the deregulation of the neurovascular unit (NVU) is important in the pathogenesis of PFBC. The recent study by Schottlaender and collaborators (2020) has added new data to foster these analyses and to enable a better understanding of this underdiagnosed and intriguing neuropsychiatric condition. A great challenge now is to design a model that explains how different pathways might lead to similar neuroimaging findings but with variable clinical outcome, and with marked severity in cases linked to MYORG and JAM2. Currently available databases of detailed gene expression in different vascular cell types from the mouse brain could be used to explore a possible integrative model.


Noble Metal Single-Atom Catalysts for the Catalytic Oxidation of Volatile Organic Compounds.
Volatile organic compounds (VOCs) are detrimental to the environment and human health and must be eliminated before discharging. Oxidation by heterogeneous catalysts is one of the most promising approaches for the VOCs abatement. Precious metal catalysts are highly active for the catalytic oxidation of VOCs, but they are rare and their high price limits large-scale application. Supported metal single-atom catalysts (SACs) have a high atom efficiency and provide the possibility to circumvent such limitations. This Review summarizes recent advances in the use of metal SACs for the complete oxidation of VOCs, such as benzene, toluene, formaldehyde, and methanol, as well as aliphatic and Cl- and S-containing hydrocarbons. The structures of the metal SACs used and the reaction mechanisms of the VOC oxidation are discussed. The most widely used SACs are noble metals supported on oxides, especially on reducible oxides, such as Mn2 O3 and TiO2 . The reactivity of most SACs is related to the activity of surface lattice oxygen of the oxides. Furthermore, several metal SACs show better reactivity and improved S and Cl resistance than the corresponding nanocatalysts, indicating that SACs have potential for application in the oxidation of VOCs. The deactivation and regeneration mechanisms of the metal SACs are also summarized. It is concluded that the application of metal SACs in catalytic oxidation of VOCs is still in its infancy. This Review aims to elucidate structure-performance relationships and to guide the design of highly efficient metal SACs for the catalytic oxidation of VOCs.


Thoracoabdominal asynchrony and paradoxical motion in Duchenne muscular dystrophy and healthy subjects during cough: A case control study.
To assess thoracoabdominal asynchrony (TAA) and inspiratory paradoxical motion at different positionings in subjects with Duchenne muscular dystrophy (DMD) versus healthy subjects during quiet spontaneous breathing (QB) and cough. This is a case control study with a matched-pair design. We assessed 14 DMD subjects and 12 controls using optoelectronic plethysmography (OEP) during QB and spontaneous cough in 3 positions: supine, supine with headrest raised at 45°, and sitting with back support at 80°. The TAA was assessed using phase angle (θ) between upper (RCp) and lower rib cage (RCa) and abdomen (AB), as well as the percentage of inspiratory time the RCp (IPRCp ), RCa (IPRCa ), and AB (IPAB ) moved in opposite directions. During cough, DMD group showed higher RCp and RCa θ (p < .05), RCp and AB θ (p < .05) in supine and 45° positions, and higher RCp and Rca θ (p = .006) only in supine position compared with controls. Regarding the intragroup analysis, during cough, DMD group presented higher RCp and AB θ (p = .02) and RCa and AB θ (p = .002) in supine and higher RCa and AB θ (p = .002) in 45° position when compared to 80°. Receiver operating characteristic curve analyzes were able to discriminate TAA between controls and DMD in RCa supine position (area under the curve: 0.81, sensibility: 78.6% and specificity: 91.7%, p = .001). Subjects with DMD yields TAA with insufficient deflation of chest wall compartments and rib cage distortion during cough, by noninvasive assessment.


Ensuring a Post-COVID Economic Agenda Tackles Global Biodiversity Loss.
The COVID-19 pandemic has caused dramatic and unprecedented impacts on both global health and economies. Many governments are now proposing recovery packages to get back to normal, but the 2019 Intergovernmental Science-Policy Platform for Biodiversity and Ecosystem Services Global Assessment indicated that business as usual has created widespread ecosystem degradation. Therefore, a post-COVID world needs to tackle the economic drivers that create ecological disruptions. In this perspective, we discuss a number of tools across a range of actors for both short-term stimulus measures and longer-term revamping of global, national, and local economies that take biodiversity into account. These include measures to shift away from activities that damage biodiversity and toward those supporting ecosystem resilience, including through incentives, regulations, fiscal policy, and employment programs. By treating the crisis as an opportunity to reset the global economy, we have a chance to reverse decades of biodiversity and ecosystem losses.


Clinical Care and Unmet Needs of Individuals With Dementia With Lewy Bodies and Caregivers: An Interview Study.
Patient-centered care requires understanding patient preferences and needs, but research on the clinical care preferences of individuals living with dementia and caregivers is sparse, particularly in dementia with Lewy bodies (DLB). Investigators conducted telephone interviews with individuals living with DLB and caregivers from a Lewy body dementia specialty center. Interviews employed a semistructured questionnaire querying helpful aspects of care and unmet needs. Investigators used a qualitative descriptive approach to analyze transcripts and identify themes. Twenty individuals with DLB and 25 caregivers participated. Twenty-three of the caregivers were spouses, 2 were daughters. Aspects of clinical care valued by individuals with DLB and caregivers included clinician time, diagnosis, education, symptom management, communication, and caring staff. Unmet needs or challenges included patient/caregiver education, education of nonspecialist clinicians and community care providers, scheduling difficulties, caregiver support, financial concerns, assistance with advance care planning and finding local resources, and effective treatments for DLB symptoms. Improving care for individuals with DLB and their families will require a multipronged strategy including education for nonspecialist care providers, increasing specialty care access, improved clinical care services, research to support disease prognosis and treatment decisions, and local and national strategies for enhanced caregiver support.


Multiplex differential display identifies a novel zinc-finger protein repressed during withdrawal from cocaine.
Multiplex differential display (MDD), a modification of differential display reverse transcriptase polymerase chain reaction (DD-PCR), was used to identify cocaine-dependent regulation of previously known and unknown gene products. Direct comparison of the MDD amplification profiles of duplicate, total RNA samples from the caudate putamen (CPu) of either vehicle or cocaine treated Sprague-Dawley rats indicated that the relative induction of a 240 bp (8G247) product, likely to represent c-fos mRNA, closely paralleled changes in c-fos mRNA as measured by Northern blot analysis. MDD and Northern blot analysis also revealed substantial repression of another PCR product (8G226) at 1 h and 1 day after repeated administration of cocaine. At 2 days after cocaine exposure, the level of 8G226 had returned to control levels. The DNA sequence of 8G226 exhibited near identity with a mouse zinc-finger protein (PZf) and is thus likely to represent a transcriptional regulator. Interestingly, the repression of 8G226 immediately after cocaine treatment is in direct contrast to the cocaine-dependent increase in expression documented for NGFI-A, another zinc-finger protein which also functions as a transcriptional regulator. Detailed characterization of the prolonged reduction in the expression of 8G226 may lead to the identification of additional regulatory pathways that produce changes in cellular response after repeated cocaine exposure.


Neural stem cell-based dual suicide gene delivery for metastatic brain tumors.
In our previous works, we demonstrated that human neural stem cells (NSCs) transduced with the cytosine deaminase (CD) gene showed remarkable 'bystander killer effect' on glioma and medulloblastoma cells after administration of the prodrug 5-fluorocytosine (5-FC). In addition, herpes simplex virus thymidine kinase (TK) is a widely studied enzyme used for suicide gene strategies, for which the prodrug is ganciclovir (GCV). To apply this strategy to brain metastasis treatment, we established here a human NSC line (F3.CD-TK) expressing the dual suicide genes CD and TK. We examined whether F3.CD-TK cells intensified the antitumor effect on lung cancer brain metastases. In vitro studies showed that F3.CD-TK cells exerted a marked bystander effect on human lung cancer cells after treatment with 5-FC and GCV. In a novel experimental brain metastases model, intravenously administered F3 cells migrated near lung cancer metastatic lesions, which were induced by the injection of lung cancer cells via the intracarotid artery. More importantly, F3.CD-TK cells in the presence of prodrugs 5-FC and GCV decreased tumor size and considerably prolonged animal survival. The results of the present study indicate that the dual suicide gene-engineered, NSC-based treatment strategy might offer a new promising therapeutic modality for brain metastases.


Obstacles to implement machine perfusion technology in routine clinical practice of transplantation: Why are we not there yet?
Machine perfusion of solid human organs is an old technique, and the basic principles were presented as early as 1855 by Claude Barnard. More than 50 years ago, the first perfusion system was used in clinical kidney transplantation. Despite the well-known benefits of dynamic organ preservation and significant medical and technical development in the last decades, perfusion devices are still not in routine use. This article describes the various challenges to implement this technology in practice, critically analyzing the role of all involved stakeholders, including clinicians, hospitals, regulatory, and industry, on the background of regional differences worldwide. The clinical need for this technology is discussed first, followed by the current status of research and the impact of costs and regulations. Considering the need for strong collaborations between clinical users, regulatory bodies, and industry, integrated road maps and pathways required to achieve a wider implementation are presented. The role of research development, clear regulatory pathways, and the need for more flexible reimbursement schemes is discussed together with potential solutions to address the most relevant hurdles. This article paints an overall picture of the current liver perfusion landscape and highlights the role of clinical, regulatory, and financial stakeholders worldwide.


Risk stratification of patients with atrial fibrillation in the emergency department.
Early and accurate risk stratification of patients with atrial fibrillation (AF) in the emergency department (ED) could aid the physician in determining a timely treatment strategy appropriate to the severity of disease. We conducted a retrospective review of 243 adult patients who presented to a tertiary ED with AF in 2017. Primary outcome studied was 30-day adverse event (a composite outcome of repeat visit to the ED, cardiovascular complications, and all-cause mortality). Secondary outcome studied was 90-day all-cause mortality. We compared the performance of the RED-AF, AFTER and CHA2DS2-VASc score by plotting receiver operating characteristic (ROC) curves and estimating the areas under curves (AUC), and assessed the potential to further improve the tools with their incorporation of new variables. Existing scoring tools had poor predictive value for 30-day adverse events, with the RED-AF score performing comparatively better, followed by the AFTER and CHA2DS2-VASc score. All scores performed collectively better to predict 90-day mortality, with the AFTER score performing the best, followed by the RED-AF and CHA2DS2-VASc score. By incorporating heart rate at initial presentation to the ED as a variable into the AFTER Score, we generated a Modified AFTER Score with superior predictive performance above existing scores for 90-day mortality. Existing scores collectively performed poorly to predict 30-day adverse outcomes, but the AFTER and Modified AFTER score showed good predictive value for 90-day mortality. Further studies should be done to validate their use in guiding clinician's disposition of patients with AF in the ED.


Association of Serum Sclerostin Level, Coronary Artery Calcification, and Patient Outcomes in Maintenance Dialysis Patients.
The objective of this study is to investigate the association between the serum sclerostin, the coronary artery calcification (CAC), and patient outcomes in maintenance dialysis patients. We performed a prospective cohort study of 65 maintenance dialysis patients in 2014, including 39 patients on peritoneal dialysis and 26 on hemodialysis, and followed up for 5 years. Parameters of mineral metabolism including bone-specific alkaline phosphatase, fibroblast growth factor 23, sclerostin, and other biochemical factors were determined at the baseline. Meanwhile, the CAC score was analyzed by cardiac computed tomography. Serum sclerostin in hemodialysis patients was significantly higher than that in peritoneal dialysis patients (632.35 ± 369.18 vs. 228.85 ± 188.92, p < 0.001). The patients with CAC were older, receiving hemodialysis, lower Kt/V, and had longer dialysis vintage, as well as higher levels of serum 25-(OH)-vit D and sclerostin. In multivariate logistic regression analysis, older age and lower Kt/V were risk factors for CAC. The area under the receiver operating characteristic curves for prediction of CAC by sclerostin was 0.74 (95% confidence interval 0.605-0.878, p = 0.03), and the cutoff value of sclerostin is 217.55 pg/mL with the sensitivity 0.829 and specificity 0.619. After 5 years of follow-up, 51 patients survived. The patients in the survival group had significantly lower age, sclerostin levels, and low CAC scores than the nonsurvival group. Old age (≥60 years, p < 0.001) and high CAC score (≥50 Agatston unit, p = 0.031) were significant risk factors for the patient survival. Sclerostin is significantly elevated in dialysis patients with CAC. But sclerostin is not a risk factor for CAC. After 5 years of follow-up, patients in the survival group are younger and have lower sclerostin levels and CAC scores. But sclerostin levels are not independent risk factors for high mortality in dialysis patients.


Preparation and crystallization of the disulfide-linked HLA-G dimer.
HLA-G is a non-classical MHC class I, which binds to inhibitory receptors, such as Leukocyte Ig-like receptors, to induce a wide range of tolerogenic immunological effects. HLA-G can be expressed as a disulfide-liked dimer both in solution and at the cell surface. However, the three-dimensional structure of the HLA-G dimer is unknown. Here, we report the crystallization of the disulfide-linked dimer form of HLA-G by adding dithiothreitol (DTT), enabling a 3.2-A data set to be collected. We also show that DTT promotes disulfide bond exchange of refolded HLA-G, whose free cysteine was protected, thus facilitating its dimerization. This technique could also be applied for disulfide-mediated dimer/multimer formation of refolded proteins harbouring free cysteines.


Loss-of-function mutations in the melanocortin 4 receptor in a UK birth cohort.
Mutations in the melanocortin 4 receptor gene (MC4R) are associated with obesity but little is known about the prevalence and impact of such mutations throughout human growth and development. We examined the MC4R coding sequence in 5,724 participants from the Avon Longitudinal Study of Parents and Children, functionally characterized all nonsynonymous MC4R variants and examined their association with anthropometric phenotypes from childhood to early adulthood. The frequency of heterozygous loss-of-function (LoF) mutations in MC4R was ~1 in 337 (0.30%), considerably higher than previous estimates. At age 18 years, mean differences in body weight, body mass index and fat mass between carriers and noncarriers of LoF mutations were 17.76 kg (95% CI 9.41, 26.10), 4.84 kg m-2 (95% CI 2.19, 7.49) and 14.78 kg (95% CI 8.56, 20.99), respectively. MC4R LoF mutations may be more common than previously reported and carriers of such variants may enter adult life with a substantial burden of excess adiposity.


Characterization of heterotrophic prokaryote subgroups in the Sfax coastal solar salterns by combining flow cytometry cell sorting and phylogenetic analysis.
Here, we combined flow cytometry (FCM) and phylogenetic analyses after cell sorting to characterize the dominant groups of the prokaryotic assemblages inhabiting two ponds of increasing salinity: a crystallizer pond (TS) with a salinity of 390 g/L, and the non-crystallizer pond (M1) with a salinity of 200 g/L retrieved from the solar saltern of Sfax in Tunisia. As expected, FCM analysis enabled the resolution of high nucleic acid content (HNA) and low nucleic acid content (LNA) prokaryotes. Next, we performed a taxonomic analysis of the bacterial and archaeal communities comprising the two most populated clusters by phylogenetic analyses of 16S rRNA gene clone library. We show for the first time that the presence of HNA and LNA content cells could also be extended to the archaeal populations. Archaea were detected in all M1 and TS samples, whereas representatives of Bacteria were detected only in LNA for M1 and HNA for TS. Although most of the archaeal sequences remained undetermined, other clones were most frequently affiliated to Haloquadratum and Halorubrum. In contrast, most bacterial clones belonged to the Alphaproteobacteria class (Phyllobacterium genus) in M1 samples and to the Bacteroidetes phylum (Sphingobacteria and Salinibacter genus) in TS samples.


GEOLOGICALLY DATED SEA BARRIERS CALIBRATE A PROTEIN CLOCK FOR AEGEAN WATER FROGS.
Reliable estimates of phylogenetic relationships and divergence times are a crucial requirement for many evolutionary studies, but are usually difficult because fossils are scarce and their interpretation is often uncertain. Frogs are fresh water animals that generally are unable to cross salt water barriers (their skin is readily permeable to both salt and water). The geologically determined ages of salt water barriers that isolate related frog populations thus provide an independent measure of the minimum date of genetic divergence between pairs of such populations. For the genetically well-studied western Palearctic water frogs (Rana esculenta group), the Aegean region provides an ideal area for determining the relationship between genetic divergence and time of spatial isolation, using a nested set of geologically determined isolation times (12,000 yr, 200,000 yr, 1.8 Myr, 2-3 Myr, and 5.2 Myr). Using 31 electrophoretic loci for 33 pairs of neighboring frog populations, a linear relationship between geologically determined isolation time and Hillis' modified Nei genetic distance was found: D*Nei = (0.04 ± 0.01) + (0.10 ± 0.01) isolation time [Myr] corresponding to an average divergence rate ("molecular clock" pace) of 0.10 D*Nei /Myr (0.10 DNei /Myr). This rate is in the range of previous estimates reported for protein electrophoretic data; the value is conservative because relatively few of the loci used are "fast evolvers" (13%; sAAT, ALB, EST-5, MPI). Removing these fast evolvers from the analysis results in 0.08 D*Nei /Myr (0.08 DNei /Myr). The confidence limits for estimation of the divergence time given the genetic distance are large, but unusually narrow for this kind of study; they permit us to estimate divergence times during the Pliocene and Miocene. Few previous studies, including sequence analyses, have provided reasonable estimates of divergence time for the Pliocene. A test using the outgroup taxa Rana perezi and Rana saharica (also isolated for 5.2 Myr by the Strait of Gibraltar) fits the calibration well: observed genetic Nei distance D*Nei = 0.55, expected D*Nei = 0.56. The calculated divergence times, based on this absolute molecular clock, suggest a series of speciation events after the Messinian (5.2 Myr), possibly triggered by the rapid ecological changes accompanying the desiccation and refilling of the Mediterranean Basin.


Isosmolar coma during parenteral alimentation with protein hydrolysate in excess of 4 gm/kg/day.
Isosmolar coma occurred during the first week of parenteral nutrition in four infants when the amount of protein hydrolysate infused was rapidly increased to or above 4 gm/kg/day. Coma developed within a 6- to 12-hour period and was characterized by (1) a normal serum osmolality, (2) an elevated urine specific gravity, and (3) the rapid reversal of the clinical signs when the protein containing solution was discontinued. A very gradual increase in protein content to a total of no more than 4 gm/kg/day is advised to provide an adequate yet safe protein load for intravenous nutrition.


Chlorido[1-(4,5-dihydro-1,3-thia-zol-2-yl-κN)ethanone thio-semicarbazonato-κN,S]nickel(II).
In the title compound, [Ni(C(6)H(9)N(4)S(2))Cl], the Ni atom is in a slightly distorted square-planar environment coordinated by a Cl atom and a deprotonated thio-semicarbazone ligand via its thia-zoline N, azomethine N and thiol-ate S atoms. Short inter-molecular N-H⋯Cl and C-H⋯S contacts are present in the crystal structure.


Geographic diffusion of digital mammography in the United States.
Examining temporal and spatial diffusion of a new technology, such as digital mammography, can provide important insights into potential disparities associated with access to new medical technologies and how quickly these technologies are adopted. Although digital mammography is currently a standard technology in the United States for breast cancer screening, its adoption and geographic diffusion, as medical facilities transitioned from film to digital units, has not been explored well. This study evaluated the geographic diffusion of digital mammography facilities from 2001 to 2014 in the contiguous United States (excluding Alaska and Hawaii) and estimated the geographic accessibility to this new technology for women aged ≥45 years at the census tract level within a 20-minute drivetime by population density, rural/urban residence, and race/ethnicity. The number of mammography units by technology type (film or digital) and density per 10,000 women were also summarized. The adoption of digital mammography advanced first in densely populated regions and last in remote rural areas. Overall, proportion of digital mammography units increased from 1.4% in 2001 to 94.6% in 2014, but since 2008, there was a decline in density of units from 2.31 per 10,000 women aged ≥45 years to 1.97 in 2014. In 2014, approximately 87% of women aged ≥45 years in the contiguous United States had accessibility to digital mammography, but this proportion was substantially lower for Native American women (67%) and rural residents (32%). Understanding the diffusion of and accessibility to digital mammography may help predict future medical technology diffusion and assess its role in geographic differences in cancer diagnosis and treatment.


Transcatheter aortic valve implantation: surgical perspectives.
Aortic valve replacement (AVR) is a routine procedure for decades to treat patients with symptomatic aortic stenosis. The introduction of transcatheter aortic valve implantation (TAVI) by Professor Alain Cribier has paved the way for minimally invasive therapeutic options for elderly and high-risk patients with aortic stenosis. Transfemoral and transapical aortic valve implantations have become routine procedures in many centres around Europe. TAVI is usually being performed together by experienced cardiologists and cardiac surgeons who build the interdisciplinary 'Heart Team'. In the future, improved devices together with advanced fusion imaging will lead to a further improvement in clinical outcomes for the sake of our patients.


An Outbreak of Coxsackievirus B Type 2 Acute Meningoencephalitis in Children, Israel, July-September 2022.
During July-September 2022, 14 children suffering from meningoencephalitis tested positive for Coxsackievirus B2 (8 cerebrospinal fluid, 9 stool samples). Mean age 22 months (range 0-60 months); 8 were males. Seven of the children presented with ataxia and 2 had imaging features of rhombencephalitis, not previously described in association with Coxsackievirus B2.


Symptomatic intrasellar arachnoid cyst: case report.
A case of a large symptomatic intrasellar arachnoid cyst with suprasellar extension is reported. A 53-year-old man was admitted because of decreased visual acuity. Magnetic resonance imaging showed a large intrasellar cyst extending into the suprasellar cistern, with compression of optic nerves. The intensity of the cyst was identical to that of the surrounding subarachnoid space on both T1-, T2-, and proton density-weighted images. Transsphenoidal surgery was performed, but subsequent refilling of the cyst required additional transcranial surgery. Analysis of the cerebrospinal fluid-like cystic fluid revealed high levels of protein and pituitary hormones. Histological study revealed that the cyst wall was composed of connective tissue and arachnoid cells, which were ultrastructurally characterized by a number of desmosomes. Diagnostic, surgical, and pathological features of intrasellar arachnoid cysts are discussed.


Case of a healthy infant born following antenatal enterovirus myocarditis and hydrops.
Fetal hydrops and myocarditis were diagnosed in a woman at 32 weeks of gestation (WG). Transplacental enterovirus infection was suspected because all other causes of myocarditis and hydrops were excluded, it was during an endemic period, and there was a setting of maternal infection (fever a few days before). We opted for in utero treatment because of the risk of resuscitating a neonate with myocarditis and hydrops. We administered dexamethasone 12mg twice for pulmonary maturation and presumed it would partially improve the myocarditis. Fetal arrhythmia was noted at 35 WG and we decided to deliver the infant as postnatal treatment of the heart disorder would be more effective. RT-PCR (ARGENE(®)) showed that the neonate's throat and anal tissues and cord blood sampled on the day of birth contained enterovirus ribonucleic acid and coxsackievirus B5, as did the mother's anal sample. Laboratory tests, heart MRI and probably brain MRI indicated neonatal enterovirus infection. Findings were normal at two-year follow-up.


The influence of near-threshold priming on metamemory and recall.
A metamemory paradigm involving the use of near-threshold visual priming is developed in which a brief flash of a previously nonrecalled answer occurs, and then the person attempts to recall the answer and/or make feeling-of-knowing judgments. The major new finding is that the feeling of knowing did not detect perceptual input from a near-threshold prime that increased the recall of otherwise nonrecallable items. This finding has two important implications: (1) The feeling of knowing is not always more sensitive than recall as an indicant of information in memory (particularly, as an indicant of small amounts of information newly deposited into memory), and (2) 'monitored' information (that the feeling of knowing would be capable of detecting, as examined in previous research) can be combined with 'nonmonitored' information (that is newly deposited into memory and that the feeling of knowing does not detect) so as to produce the successful recall of an otherwise nonrecallable item.


Lead and cadmium exposure alters shell morphogenesis in a single-chambered, agglutinated foraminiferan protist.
Changes to calcareous foraminiferal shell morphology are well documented in heavy metal-polluted marine environments, however less is known about how these toxicants affect agglutinated foraminifera, particularly single-chambered (monothalamid) species. Here we used an agglutinated monothalamic foraminifer, Astrammina rara, to study shell morphogenesis during exposure to lead (Pb) and cadmium (Cd). Isolated cell bodies incubated with artificial sediment and control, Pb-, or Cd-spiked artificial seawater constructed new agglutinated shells in four weeks. Time-lapse recordings showed normal motile behavior during treatments. SEM imaging of reconstructed shells, however, revealed dramatic deformations in the bioadhesive of Pb-exposed shells, and less so in Cd-exposed shells. ICP-MS analysis of the isolated shells showed elevated levels of Pb, but not Cd, in the bioadhesive of treated specimens, indicating that the two metals exert their effects differentially. These findings show that certain agglutinated foraminifera may be useful indicator species in studies of heavy metal-polluted benthic marine environments.


Dexmedetomidine and Magnesium Sulfate as Adjuvant to 0.5% Ropivacaine in Supraclavicular Brachial Plexus Block: A Comparative Evaluation.
Dexmedetomidine and magnesium sulfate (MgSO4) as an adjuvant to local anesthetics and ultrasound guidance improves the quality of peripheral nerve block. We aim to compare the efficacy of dexmedetomidine and MgSO4 as an adjuvant to ropivacaine in supraclavicular brachial plexus block. Sixty patients undergoing upper extremity orthopedic surgery were randomly allocated into three groups of 20 each. Group A received 29 mL of 0.5% ropivacaine plus 1 mL of normal saline, Group B received 29 mL of 0.5% ropivacaine plus 1 mL dexmedetomidine (100 μg), and Group C received 29 mL of 0.5% ropivacaine plus 1 mL MgSO4 (250 mg). Onset and duration of sensory and motor block, duration of analgesia, quality of anesthesia, total 24 h analgesic consumption, sedation, and complications were recorded. Software SPSS-16 was used for statistical analysis. The onset of sensory block and motor block was fastest for Group B, followed by Group C and slowest in Group A. The duration of sensory block and motor block was maximum for Group B, followed by Group C and minimum for Group A. The duration of analgesia was maximum for Group B, followed by Group C and minimum for Group A. Analgesic consumption was minimum for Group B. Quality of anesthesia was better in Group B than other groups. The visual analog scale was higher in Group A than other groups. Group B reported higher sedation score. Dexmedetomidine provides earlier onset of sensory and motor block as well as prolonged duration of sensory and motor blocks and duration of analgesia is longer and postoperative rescue analgesia is less as compared to patients receiving MgSO4. The incidence of hypotension and bradycardia and sedation score was higher with dexmedetomidine.


[Peritoneal carcinomatosis of gastric cancer : Treatment options for peritoneal carcinomatosis of gastric cancer].
Gastric cancer is one of the most aggressive malignant diseases of the gastrointestinal tract with a high rate of metastasis. Peritoneal metastasis occurs in up to 60% of all patients and synchronously in up to 30% in locally advanced gastric cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been an established treatment option in selected patients for several years, as the HIPEC serves as an alternative administration route. This article presents a schematic display of the various treatment options depending on the extent of peritoneal carcinomatosis in a gastric cancer. A literature search and analysis of the current literature on the treatment of gastric cancer with peritoneal metastases were carried out. A differentiation was made between limited and extensive peritoneal carcinomatosis together with the appropriate treatment strategy. Principally, individual systemic chemotherapy is the backbone of treatment of gastric cancer with peritoneal metastases. In selected patients and in cases of limited peritoneal carcinomatosis, CRS and HIPEC can be conducted and survival is improved; however, CRS is still contraindicated in cases of extensive peritoneal carcinomatosis and in exceptional cases pressurized intraperitoneal aerosol chemotherapy (PIPAC) can be carried out. In selected patients CRS and HIPEC can lead to an improvement with respect to overall and disease-free survival. In cases of extensive peritoneal carcinomatosis, individualized chemotherapy remains the major treatment option.


Development of a MET-targeted single-chain antibody fragment as an anti-oncogene targeted therapy for breast cancer.
The usage of monoclonal antibodies (mAbs) and antibody fragments, as a matter associated with the biopharmaceutical industry, is increasingly growing. Harmonious with this concept, we designed an exclusive modeled single-chain variable fragment (scFv) against mesenchymal-epithelial transition (MET) oncoprotein. This scFv was newly developed from Onartuzumab sequence by gene cloning, and expression using bacterial host. Herein, we examined its preclinical efficacy for the reduction of tumor growth, invasiveness and angiogenesis in vitro and in vivo. Expressed anti-MET scFv demonstrated high binding capacity (48.8%) toward MET-overexpressing cancer cells. The IC50 value of anti-MET scFv against MET-positive human breast cancer cell line (MDA-MB-435) was 8.4 µg/ml whereas this value was measured as 47.8 µg/ml in MET-negative cell line BT-483. Similar concentrations could also effectively induce apoptosis in MDA-MB-435 cancer cells. Moreover, this antibody fragment could reduce migration and invasion in MDA-MB-435 cells. Grafted breast tumors in Balb/c mice showed significant tumor growth suppression as well as reduction of blood-supply in response to recombinant anti-MET treatment. Histopathology and immunohistochemical assessments revealed higher rate of response to therapy. In our study, we designed and synthetized a novel anti-MET scFv which could effectively suppress MET-overexpressing breast cancer tumors.


Conservation and diversity of the eukaryotic SAGA coactivator complex across kingdoms.
The SAGA complex is an evolutionarily conserved transcriptional coactivator that regulates gene expression through its histone acetyltransferase and deubiquitylase activities, recognition of specific histone modifications, and interactions with transcription factors. Multiple lines of evidence indicate the existence of distinct variants of SAGA among organisms as well as within a species, permitting diverse functions to dynamically regulate cellular pathways. Our co-expression analysis of genes encoding human SAGA components showed enrichment in reproductive organs, brain tissues and the skeletal muscle, which corresponds to their established roles in developmental programs, emerging roles in neurodegenerative diseases, and understudied functions in specific cell types. SAGA subunits modulate growth, development and response to various stresses from yeast to plants and metazoans. In metazoans, SAGA further participates in the regulation of differentiation and maturation of both innate and adaptive immune cells, and is associated with initiation and progression of diseases including a broad range of cancers. The evolutionary conservation of SAGA highlights its indispensable role in eukaryotic life, thus deciphering the mechanisms of action of SAGA is key to understanding fundamental biological processes throughout evolution. To illuminate the diversity and conservation of this essential complex, here we discuss variations in composition, essentiality and co-expression of component genes, and its prominent functions across Fungi, Plantae and Animalia kingdoms.


Genetic characterization of the temperature-sensitive and suppression phenotypes of Escherichia coli mutant N4316.
Escherichia coli mutant N4316 is temperature sensitive and exhibits temperature-dependent suppression. These phenotypes are due to separate genes, as shown by reversion and mapping studies. The suppressor mutation was mapped and lies near argF.


Chromatographic separation of two acid phosphatases from rat bone.
Extracts of tibiae of suckling rats were prepared with 0.3 M KCl containing 0.1% Triton X-100 and were chromatographed with CM-52 cellulose. Most of the acid phosphatase activity determined with p-nitrophenylphosphate (p-NPP) was bound to the cellulose and could be eluted with a sodium acetate buffer gradient in 2 distinct peaks. The major peak, E2, was bound strongly to the cellulose and showed high activity with p-NPP and inorganic pyrophosphate (P-Pi), but only slight activity with beta-glycerophosphate (beta-GP) and was unaffected by tartrate. The minor peak, E1, was weakly bound to the adsorbent, showed equal activity with p-NPP and beta-GP, but negligible activity with P-Pi and was completely inhibited by tartrate. These results support earlier evidence suggesting that bone contains at least 2 different acid phosphatases and that the more abundant enzyme may function as a pyrophosphatase.


The correlation between training and skill of the surgeon and reoperation rate for persistent cleft palate speech.
The correlation between the surgeons training and skill and the speech after primary repair was tested using the reoperation rate as a measure for success in 439 cleft palate/cleft lip and palate (CP/CLP) patients operated at the average age of 22 months by 4 specialists and 4 residents. The reoperation rate for residents was 11-60% (av. 36) and for specialists 13-31% (av. 19). The relative reoperation rates in CP/CLP were 20/19% for specialists but 35/38% residents. In groups consisting of the four with the best (A) and the four with the worst results (B) the reoperations rate in group A was 16% for CP and 13% for CLP, but in group B 37/44%. As the residents became specialists, the degree of their improvement varied greatly. Thus both the training and skill are important for the patients speech, but they are not necessarily synonymous terms.


(5-Bromo-2-meth-oxy-phen-yl)(4-ethyl-cyclo-hex-yl)methanone.
In the title compound, C(16)H(21)BrO(2), the cyclo-hexane ring is in a chair conformation and its least-squares plane is at an angle of 61.3 (9)° to the benzene ring. The crystal packing is stabilized by weak π-π stacking inter-actions [centroid-centroid distance = 3.697 (9) Å] between the bromo-meth-oxy-phenyl rings of neighbouring mol-ecules.


Preclinical screening of anti-HER2 nanobodies for molecular imaging of breast cancer.
Accurate determination of tumor human epidermal growth factor receptor 2 (HER2)-status in breast cancer patients is possible via noninvasive imaging, provided adequate tracers are used. In this study, we describe the generation of a panel of 38 nanobodies, small HER2-binding fragments that are derived from heavy-chain-only antibodies raised in an immunized dromedary. In search of a lead compound, a subset of nanobodies was biochemically characterized in depth and preclinically tested for use as tracers for imaging of xenografted tumors. The selected compound, 2Rs15d, was found to be stable and to interact specifically with HER2 recombinant protein and HER2-expressing cells in ELISA, surface plasmon resonance, flow cytometry, and radioligand binding studies with low nanomolar affinities, and did not compete with anti-HER2 therapeutic antibodies trastuzumab and pertuzumab. Single-photon-emission computed tomography (SPECT) imaging quantification and biodistribution analyses showed that (99m)Tc-labeled 2Rs15d has a high tumor uptake in 2 HER2(+) tumor models, fast blood clearance, low accumulation in nontarget organs except kidneys, and high concomitant tumor-to-blood and tumor-to-muscle ratios at 1 h after intravenous injection. These values were dramatically lower for an irrelevant control (99m)Tc-nanobody and for (99m)Tc-2Rs15d targeting a HER2(-) tumor.


Volume measurement of multiple sclerosis lesions with magnetic resonance images. A preliminary study.
The ability to visualise multiple sclerosis lesions in vivo with magnetic resonance imaging suggests an important role in monitoring the course of the disease. In order to help the long-term assessment of prospective treatments, a semi-automated technique for measuring lesion volume has been developed to provide a quantitative index of disease progression. Results are presented from a preliminary study with a single patient and compared to measurements taken from lesion outlines traced by a neuroradiologist, two neurologists and a technician. The semi-automated technique achieved a precision of 6% compared to a range of 12-33% for the manual tracing method. It also reduced the human interaction time from at least 60 min to 15 min.


[Risk factors and incidence of relapse in lung tuberculosis patients].
To determine the incidence of relapse in patients with lung tuberculosis and its associated risk factors. A follow up study was conducted with 237 patients who were cured after receiving treatment in rural medical facilities from the State of Chiapas. The global incidence of relapse was 1.04 cases per 100 month/person. The risk factors for relapse were lack of knowledge about treatment (OR = 2.28; 95% CI = 1.06-4.89); drug adverse effects (OR = 2.78; 95% CI = 1.31-5.90), waiting time for more than 15 minutes to receive medical care (OR = 3.07; 95% CI = 1.06-12.94) and lack of medical supervision (OR = 4.77; 95% CI = 1.30-17.41). Most of the risk factors for relapse are susceptible to modification and are related with the quality of medical care provided to lung tuberculosis patients.


Rapid analysis of titer, aggregate, and intact mass of antibody therapeutics using automated multi-dimensional liquid chromatography coupled with native mass spectroscopy.
Monoclonal antibodies are tetrameric complex proteins, primarily produced using mammalian cell culture. Attributes such as titer, aggregates, and intact mass analysis are monitored during process development/optimization. In the present study, a novel workflow such that the Protein-A affinity chromatography is performed in the first dimension for purification and titer estimation, whereas size exclusion chromatography is employed in the second dimension to characterize size variants using native mass spectrometry. The present workflow offers a significant advantage over the traditionally used standalone Protein-A affinity chromatography followed by size exclusion chromatography analysis in that it can monitor these four attributes in 8 min while requiring a minimal sample size (10-15 μg) and not requiring any manual peak collection. In contrast, the traditional standalone approach requires manual collection of eluted peaks in Protein-A affinity chromatography followed by buffer exchange to a mass-compatible buffer, which can take up to 2-3 h with considerable risk of sample loss, degradation, and induced modifications. As the biopharma industry moves to make analytical testing efficient, we believe that the approach proposed here would be of significant interest due to its ability to monitor multiple process and product quality attributes in a single workflow and via rapid analysis.


Utilisation of immunoglobulin in New Zealand.
Immunoglobulin is an expensive and scarce resource and usage is increasing worldwide. Immunoglobulin is used to treat a variety of clinical conditions, particularly primary and acquired immunodeficiencies and immune-mediated neurological disorders. As immunoglobulin usage continues to increase, plasma collection must increase accordingly in order to sustain immunoglobulin production. The New Zealand Blood Service (NZBS) is the provider of immunoglobulin in New Zealand (NZ). Information regarding national immunoglobulin usage warrants analysis given the rise in usage. To review immunoglobulin usage in NZ with a focus on the trend in the amount used, number of patients, clinical indications and compliance with international guidelines. A comparison with international immunoglobulin usage was performed. The impact on national plasma collection was reviewed. Data on immunoglobulin usage, number of patients and plasma collection over the past decade were obtained from the NZBS Tableau database. Data from international literature were reviewed. Immunoglobulin usage in NZ has been increasing over the past decade, with an annual growth rate of 6.4%. The three main indications for immunoglobulin are primary immunodeficiency disorders, chronic inflammatory demyelinating polyneuropathy (CIDP) and acquired hypogammaglobulinaemia secondary to haematological malignancies. Prominent growth in usage is evident for CIDP and acquired hypogammaglobulinaemia. Immunoglobulin usage in NZ is low compared with other countries, such as Australia and the United States. There has been a marked increase in plasma donations in order to keep up with immunoglobulin demand. Immunoglobulin is a strategic resource and appropriate usage is critical to regulate demand.


[Total glucosides of peony as adjuvant therapy for prevention of cardiac allograft rejection in rats].
To evaluate the role of total glucosides of peony (TGP) as adjuvant therapy for prevention of cardiac allograft rejection in rats. Rats with cardiac allograft were randomly divided into control group, tacrolimus-treated group, TGP-treated group and tacrolimus plus TGP-treated group. Graft survival time was observed. Allografts in some cases were examined by histological study seven days after transplantation. At the same time, the levels of CD4(+) and CD8(+) T cell subsets in peripheral blood were examined by using flow cytometry; the hepatic function and renal function of recipients were also tested. The graft survival time of the tacrolimus-treated group and tacrolimus plus TGP-treated group was (11.14+/-1.57) d and (13.57+/-1.99) d, respectively. The graft survival time of the tacrolimus plus TGP-treated group was longer than that of the tacrolimus-treated group (P<0.05). The histological study showed that the rejection of the tacrolimus plus TGP-treated group was slighter than that of the tacrolimus-treated group. The levels of CD4(+) T cell subset in the peripheral blood of the tacrolimus-treated and tacrolimus plus TGP-treated groups were (38.71+/-5.15)% and (32.43+/-4.39)% respectively 7 days after transplantation. The level of CD4(+) T cell subset in the tacrolimus plus TGP-treated group was lower than that in the tacrolimus-treated group (P<0.05). The level of CD8(+) T cell subset and the hepatic and renal function had no significant differences between the tacrolimus-treated group and the tacrolimus plus TGP-treated group. Effects of tacrolimus plus TGP in prevention of rejection are better than tacrolimus monotherapy in rats with cardiac allograft and without increasing side effects.


Autonomic nervous system function in young children with functional abdominal pain or irritable bowel syndrome.
Adults with irritable bowel syndrome (IBS) have been reported to have alterations in autonomic nervous system function as measured by vagal activity via heart rate variability. Whether the same is true for children is unknown. We compared young children 7 to 10 years of age with functional abdominal pain (FAP) or IBS to healthy children (HC) and explored the relationship of vagal activity and sympathovagal balance to psychological distress and stool type. Children completed questionnaires, kept a 2-week pain/stool diary, and wore a 24-hour Holter monitor to assess vagal activity. Group comparisons on vagal activity were controlled for age and body mass index. Indicators of vagal activity and sympathovagal balance did not differ between FAP/IBS children (70 girls, 30 boys) and HC (44 girls, 18 boys). Psychological distress measures were generally higher in FAP/IBS than HC, primarily in girls. Exploratory analyses suggest a potential negative correlation between vagal activity and psychological distress in FAP/IBS girls but not boys. In contrast to reports in women, no differences were found in vagal activity between FAP/IBS and HC. Preliminary findings suggest that in girls with FAP/IBS there is an inverse relationship between vagal activity and psychological distress. The results from this study suggest a possible relationship between emotional state and vagal activity in prepubertal girls (but not boys) with FAP/IBS. Age and/or duration of symptoms may explain our contrasting findings versus adults with IBS.


Natural Disasters Are Prejudiced Against Disadvantaged and Vulnerable Populations: The Lack of Publicly Available Health-Related Data Hinders Research at the Cusp of the Global Climate Crisis.
Natural disasters often affect the most vulnerable countries/communities around the world. However, within the same countries/communities, the impact of natural disasters is far greater on disadvantaged populations. We investigate how wildfires affect asthma prevalence in different populations across California. Our results indicate that although there is no discernible relationship between wildfires and asthma prevalence for California's population as a whole, wildfires and asthma prevalence in Black and senior populations have a strong relationship. We believe there is an urgent need to make high-resolution health-related data publicly available for in-depth analyses of climate change impacts on society and disadvantage communities.


Black Race Is Associated With Higher Rates of Early-Onset End-Stage Renal Disease and Increased Mortality Following Liver Transplantation.
Black race is a risk factor for end-stage renal disease (ESRD). Racial disparities in the risks of early and long-term renal complications after liver transplantation (LT) have not been systematically studied. This study evaluated racial differences in the natural history of acute and chronic renal insufficiency after LT. This was a retrospective single-center cohort study of 763 non-Hispanic White and 181 Black LT recipients between 2008 and 2017. Black race was investigated as an independent predictor of the following outcomes: (1) receipt and duration of early post-LT hemodialysis and (2) time to post-LT ESRD. The interaction of race and post-LT ESRD on survival was also studied. Black recipients had higher rates of pre-LT hypertension (P < 0.001), but diabetes mellitus and renal function before LT were not different by race (all P > 0.05). Overall, 15.2% of patients required early hemodialysis immediately after LT with no difference by race (covariate-adjusted odds ratio, 0.89; P = 0.71). Early dialysis discontinuation was lower among Black recipients (covariate-adjusted hazard ratio [aHR], 0.47; P = 0.02), whereas their rate of post-LT ESRD was higher (aHR, 1.91; P = 0.005). Post-LT survival after ESRD was markedly worse for Black (aHR, 11.18; P < 0.001) versus White recipients (aHR, 5.83; P < 0.001; interaction P = 0.08). Although Black and White LT recipients had comparable pretransplant renal function, post-LT renal outcomes differed considerably, and the impact of ESRD on post-LT survival was greater for Black recipients. This study highlights the need for an individualized approach to post-LT management to improve outcomes for all patients.


A melanoma patient with macrophage-cancer cell hybrids in the primary tumor, a lymph node metastasis and a brain metastasis.
In 1911 it was proposed that cancer might result from fusion and hybridization between macrophages and cancer cells. Using immunohistochemistry it was determined that essentially all solid tumors expressed macrophage-like molecules on their cell surface. More recently we have used forensic (STR) genetics that allows one to detect DNA from more than one individual in the same sample. By studying biopsies from individuals receiving allogeneic stem cell transplants and later developed solid tumor metastases, we were able to detect both donor and patient DNA sequences suggesting that hybrids were present. Previously we found hybrids in biopsies of a renal cell carcinoma, a melanoma in a brain metastasis and a melanoma in a primary tumor with lymph node metastases. Here we have traced hybrids from a primary melanoma to an axillary lymph node to a brain metastasis. This is the first time that the entire metastatic process has been documented.


The problem of post-psychotic schizophrenic depressions and their pharmacological induction. Long-term studies with fluspirilene and penfluridol and single-blind trial with fluphenazine-decanoate and flupenthixol-decanoate.
The authors discuss the historical aspects, as well as the various etiological and clinical factors which contribute to the so-called pharmacogenically induced depressions during treatment by means of neuroleptics generally, and long-term neuroleptics especially. An open study on 161 schizophrenic patients treated by means of fluspirilene and 123 patients treated by means of penfluridol is described. A single blind trial on 48 patients, by means of fluphenazine-decanoate and flupenthixol-decanoate, which compares the possible depression-inducing or antidepressant activity of the above drugs, is presented. The criteria for evaluating drug-induced depressions and their two clinical types are discussed.


Effective sorption of atrazine by biochar colloids and residues derived from different pyrolysis temperatures.
Biochar has attracted much attention, which owns many environmental and agronomic benefits, including carbon sequestration, improvement of soil quality, and immobilization of environmental contaminants. Biochar has been also investigated as an effective sorbent in recent publications. Generally, biochar particles can be divided into colloids and residues according to particle sizes, while understanding of adsorption capacities towards organic pollutants in each section is largely unknown, representing a critical knowledge gap in evaluations on the effectiveness of biochar for water treatment application. Scanning electron microscopy (SEM) images, X-ray diffraction (XRD), Raman spectra, Fourier-transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and Brunauer-Emmett-Teller (BET) method are used to examine the structures and surface properties of biochar colloids and residues derived from corn straws prepared at different pyrolysis temperatures. Also, their roles in atrazine (a typical organic pollutant) removal are investigated by batch adsorption experiments and fitted by different kinetic and thermodynamic models, respectively. The adsorption capacities of biochar colloids are much more than those of residues, resulting from the colloids containing abundant oxygen functional groups and mineral substances, and the adsorption capacities of biochar colloids and residues increase with the increase of pyrolysis temperatures. The highest adsorption performance of 139.33 mg g-1 can be obtained in biochar colloids prepared at 700 °C, suggesting the important functions of biochar colloids in the application of atrazine removal by biochar.


Finding a receptor design for selective recognition of perrhenate and pertechnetate: hydrogen vs. halogen bonding.
Receptors bearing hydrogen and halogen bond donors for recognition of perrhenate and pertechnetate were designed and studied. Acyclic hosts with N-H and C-H binding sites showed the best selectivity for TcO4- and ReO4- over spherical and more basic tetrahedral anions.


Comparison of crosspoint and least-squares regression methods in computation of membrane protein flux parameters from lymph flux analysis.
To compute two parameters of capillary protein transport of reflection coefficient (sigma) and permeability--surface area product (PS), two major methods have been employed. The first, or crosspoint method, uses two sets of lymph flow (Jv) and lymph/plasma protein concentration ratios (R) and solves the irreversible thermodynamic relationship between sigma and PS by simultaneous solution. The second, or least squares method, analyzes the total R versus Jv curve by finding a best fit of all points to the irreversible thermodynamic relationship of R versus Jv. Three theoretical membranes were analyzed with both methods by imposing random errors of 10 or 20% in R and Jv. It was found that such errors, especially in R, were associated with substantial decreases in the percent of successful computations by the crosspoint method. In tight membranes (sigma = 0.9) both methods gave comparable values. For intermediate (sigma = 0.5) and loose membranes (sigma = 0.2) the least-squares method was less specific than the crosspoint method, since up to 9% of random values of R and Jv would be included within the 95% limits for the method. Moreover, attributing homogeneous variance to input data and sampling Jv at geometric intervals exaggerated the variability of the least-squares method output parameters over those obtained by the crosspoint method. Because of nonspecificity, and the fact that the least squares method does not allow for the possibility that sigma and PS are direct functions of hydrostatic capillary pressure or Jv, the crosspoint method appears superior to the least-squares method for computation of sigma and PS from R and Jv.


Biosynthesis of the subcomponents C1q, C1r and C1s of the first component of complement (C1) by guinea pig hepatocyte primary cultures.
Thus far, the synthesis of C1q by liver cells has not been demonstrated. To investigate this possibility, viable hepatocytes were isolated from the liver of guinea pigs and primary cultures were established. The cells (10(6) cells/ml) were cultured under serum-free conditions for 8 days and the culture medium was changed every 24 h. The few contaminating Kupffer cells were lysed by preincubating the cell cultures with a monoclonal (22C4-8) antibody directed against a nonpolymorphic Ia determinant and preabsorbed rabbit serum. The hemolytic activity of C1 and its subcomponents C1q and C1r/C1s was tested in the supernatants. Guinea pig hepatocyte primary cultures synthesize and secrete up to 3 X 10(3) effective C1q molecules/cell/24 h and 34 X 10(3) effective C1r/C1s molecules/cell/24 h. The synthesis of C1q and C1r/C1s could be reversibly inhibited by cycloheximide (50 micrograms/ml). Furthermore, to demonstrate de novo synthesis of the C1q subcomponent, endogeneous labeling with 3H-proline (or 14C-proline) was performed. The immunoprecipitated C1q from cellular lysates and culture medium was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Compared to biosynthetically labeled guinea pig C1q from peritoneal macrophages, three corresponding bands (30, 28 and 24 kDa, respectively) were detectable in the fluorograph. The data show that guinea pig hepatocytes are able to synthesize C1 subcomponents, whereby the synthesis of C1q and C1r/C1s occurs independently.


Econometric ARIMA methodology to elucidate the evolution of trends in nosocomial antimicrobial resistance rates in the European Union.
Infections with bacteria harbouring resistance to cephalosporins or fluoroquinolones (FQ) constitute a serious hazard to human health. To establish a methodology based on econometric analysis and the largest European Union (EU) resistance database (EARS-Net), to model nosocomial antimicrobial resistance (AMR) in the EU and to detect tendency changes, steps or peaks. The contribution of legislation based on third-generation cephalosporin (3GC) and FQ class referrals to resistance rate patterns is evaluated. Resistance to 3GC and FQ was examined in nosocomial Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa in at least 25 out of 30 EU countries (> 94% population coverage), weighted by their mean annual population, between 2006 and 2016. Autoregressive integrated moving average (ARIMA) model analysis, inspired by Box-Jenkins methodology, was prepared to adjust series to a mathematical model to detect hypothetical changes in the general behaviour. To the best of the authors' knowledge, this is the first study to use ARIMA with interventions to model overall nosocomial AMR data compiled in EARS-Net. Econometric ARIMA models statistically prove the occurence of slowdowns and reversions in the increasing trend of AMR prevalence in nosocomial E. coli and K. pneumoniae to 3GC and FQ, as well as resistance of P. aeruginosa to 3GC. The resistance of P. aeruginosa to FQ exhibited a descending slope. The presented decreasing trends constitute noteworthy milestones in tackling AMR in Europe.


Intubation with a Tritube to avoid peri-operative tracheostomy in open airway surgery.
This paper reports a case of chondrosarcoma deriving from the left arytenoid cartilage that was resected via an anterior laryngofissure using the Tritube in situ, thus eliminating the need for a (temporary) tracheostomy. A 49-year-old male with a chondrosarcoma deriving from the left arytenoid was treated with local resection of the tumour through an anterior laryngofissure. The intralaryngeal lumen was too small for a normal endotracheal tube. Using the Tritube (outer diameter, 4.4 mm), the patient could be intubated and ventilated adequately during the procedure. The Tritube did not obstruct the surgical view during the procedure. The Tritube can be used for intubation and ventilation even in patients with a very narrow airway lumen, and does not obstruct the field of view during open laryngeal surgery, thereby avoiding the need for peri-operative tracheostomy.


Implementation of a motivational interviewing-based decision tool to improve childhood vaccination rates: Pilot study protocol.
Parental concerns regarding the safety and efficacy of vaccines have been on the rise over the past decade, resulting in a decline in comprehensive vaccine coverage in children. Healthcare practitioners face many challenges when recommending childhood vaccinations, with many parents refusing vaccination due to these and other concerns. Effective communication strategies and tools can equip providers to communicate with vaccine hesitant parents, but validated tools are currently lacking. This study aims to develop a validated parental communication tool utilizing motivational interviewing to increase vaccination adherence in children ages 6 years and younger. The MOTIVE (Motivational Interviewing Tool to Improve Vaccination Adherence) tool will first be developed based on the most recent literature regarding vaccine hesitancy and related health beliefs. Following tool development, the tool will be reviewed via an external review process to ensure practicality of the tool for use in clinical practice. In implementing the MOTIVE tool, providers and clinic staff will be trained regarding vaccine hesitancy and motivational interviewing. The tool will then be implemented in routine well-child appointments. The primary outcome of this study is the percentage of children 0-6 years of age completing all recommended doses of the core vaccine series after implementation of the MOTIVE tool as compared to prior vaccination years. Secondary outcomes will also include parental attitudes towards vaccines and provider knowledge regarding motivational interviewing components and vaccine hesitancy. Following completion of this study, the MOTIVE tool will be made available for other providers for use in their own clinical practice. The availability of effective communication tools will allow healthcare providers to engage in productive conversations regarding vaccination, aiming to increase vaccine uptake.


Effects of caffeine, cyclic 3', 5' adenosine monophosphate and cyclic 3', 5' guanosine monophosphate in the development of the mycelial form of Sporothrix schenckii.
The kinetics of the development of the mycelial form of Sporothrix schenckii from yeast cells and conidia in a minimal basal medium with glucose at pH 4.0 and 25 degrees C were established. Germ tube formation was used as the index of germination for both yeast cells and conidia. Yeast cells were first observed to develop germ tubes after 3 h of incubation, reaching 92 +/- 5%, after 12 h of incubation. Germ tubes were first detected in conidia after 9 h of incubation, and 12 h after inoculation 92 +/- 6% of the conidia had germ tubes. After 24 h of incubation, fully developed, sporulating mycelia were observed from both yeast cells and conidia. A delay in germ tube formation from yeast cells was observed when But2cAMP (10 mM) and But2cGMP (10 mM) were added to the medium. Also the addition of caffeine, a cyclic nucleotide phosphodiesterase inhibitor, inhibited the yeast to mycelial transition. Conidial germination into the mycelial form was also inhibited when cAMP, But2cAMP and caffeine were added to the medium. These results suggest the possible involvement of cyclic nucleotides in the control of dimorphism in S. schenckii.


ECM2, a prognostic biomarker for lower grade glioma, serves as a potential novel target for immunotherapy.
Extracellular matrix protein 2 (ECM2), which regulates cell proliferation and differentiation, has recently been reported as a prognostic indicator for multiple cancers, but its value in lower grade glioma (LGG) remains unknown. In this study, LGG transcriptomic data of 503 cases in The Cancer Genome Atlas (TCGA) database and 403 cases in The Chinese Glioma Genome Atlas (CGGA) database were collected to analyze ECM2 expression patterns and the relationship with clinical characteristics, prognosis, enriched signaling pathways, and immune-related markers. In addition, a total of 12 laboratory samples were used for experimental validation. Wilcoxon or Kruskal-Wallis tests demonstrated highly expressed ECM2 in LGG was positively associated with malignant histological features and molecular features such as recurrent LGG and isocitrate dehydrogenase (IDH) wild-type. Also, Kaplan-Meier (KM) curves proved high ECM2 expression could predict shorter overall survival in LGG patients, as multivariate analysis and meta-analysis claimed ECM2 was a deleterious factor for LGG prognosis. In addition, the enrichment of immune-related pathways for ECM2, for instance JAK-STAT pathway, was obtained by Gene Set Enrichment Analysis (GSEA) analysis. Furthermore, positive relationships between ECM2 expression with immune cells infiltration and cancer-associated fibroblasts (CAFs), iconic markers (CD163), and immune checkpoints (CD274, encoding PD-L1) were proved by Pearson correlation analysis. Finally, laboratory experiments of RT-qPCR and immunohistochemistry showed high expression of ECM2, as well as CD163 and PD-L1 in LGG samples. This study identifies ECM2, for the first time, as a subtype marker and prognostic indicator for LGG. ECM2 could also provide a reliable guarantee for further personalized therapy, synergizing with tumor immunity, to break through the current limitations and thus reinvigorating immunotherapy for LGG. AVAILABILITY OF DATA AND MATERIALS: Raw data from all public databases involved in this study are stored in the online repository (chengMD2022/ECM2 (github.com)).