Stereocontrol by a pair of epimeric sugar-derived ligands of the coordination sphere of copper(II) complexes.
A pair of novel C3-epimeric sugar-derived ligands (glycoligands) with a neutral N4O donor set was synthesized. Copper(II) complexes of both ligands were obtained and characterized by X-ray crystallography. Cyclic voltammetry, electron paramagnetic resonance, and UV-vis spectroscopies showed similar electronic properties. Mirror-image CD spectra were obtained for the Cu(II) d-d band, indicating an enantiomeric character of the coordination sphere, which has been rationalized structurally. This example shows the possible predetermination of stereochemistry for complexes by ligands based on a glycoscaffold.


Near field focusing by edge diffraction: publisher's note.
This publisher's note corrects an error in the reference section of Opt. Lett.43, 4053 (2018)OPLEDP0146-959210.1364/OL.43.004053.


Regulation of ribosomal protein S6 kinase in human mammary tumor cells: effect of estrogen, growth factors and phorbol ester.
Growth of human mammary tumor cells ZR-75-1 is stimulated by estradiol (E2), epidermal growth factor (EGF) and insulin-like growth factor I (IGF-I). In these cells ribosomal protein S6 kinase is activated by EGF, IGF-I, insulin and phorbol 12-myristate 13-acetate (TPA) but not by E2. The human mammary tumor cell line MDA-MB 231, which is E2-receptor negative, has receptors for EGF, IGF-I and insulin but is unresponsive to these factors in terms of growth and S6 kinase activation. The role of protein kinase C (PKC) in the activation of S6 kinase by growth factors and TPA was investigated in ZR-75-1 cells. Down regulation of PKC activity by treatment with TPA for 48-h blocks the stimulation of S6 kinase by TPA but leaves the activation by EGF, IGF-I and insulin unaffected. In intact ZR-75-1 cells staurosporine blocks activation of S6 kinase by EGF and TPA, however with different IC50. The results show that S6 kinase is not activated by estradiol, that its activation by EGF, IGE-I and insulin does not depend on the presence of PKC activity and that its activation by TPA is mediated by a different (PKC-dependent) pathway.


Non-thrombotic complications of PTFE grafts for haemodialysis.
In a consecutive series of 76 PTFE grafts (37 Impra and 39 Gore-Tex), 30 non-thrombotic complications were observed. Twenty-one (70%) of these grafts could be salvaged either by conservative means (2) or by an aggressive surgical approach (19). The median survival time of the salvaged grafts was 12 months. Only nine grafts (30%) were lost as a result of the complications. Lesions caused by punctures techniques seemed more frequent in Impra grafts than in Gore-Tex grafts. Apart from this observation it is concluded that an aggressive surgical approach to non-thrombotic complications in PTFE grafts is worthwhile.


The ribonuclease activity of the cytotoxin alpha-sarcin. The characteristics of the enzymatic activity of alpha-sarcin with ribosomes and ribonucleic acids as substrates.
The ribonuclease activity of the cytotoxic protein alpha-sarcin has been characterized. When rat liver ribosomes or 60 S ribosomal subunits were the substrates, alpha-sarcin cleaved a single oligonucleotide of about 488 residues, the alpha-fragment, from the 3' end of 28 S rRNA. In contrast, 40 S ribosomal subunits were not affected by alpha-sarcin. The alpha-fragment was cleaved from 28 S rRNA in 80 S ribosomes when the concentration of alpha-sarcin was 3 x 10(-8) M and the toxin retained its specificity even when the concentration was 3 x 10(-5) M. The turnover number (kcat) for the reaction of alpha-sarcin with ribosomes was 55 min-1, establishing that the toxin acts catalytically. When total rRNA or 28 S rRNA was the substrate, alpha-sarcin caused extensive progressive digestion of the nucleic acids; however, no formation of the alpha-fragment occurred. The extent of the digestion of 28 S rRNA was related to the concentration of alpha-sarcin, but the amount of the toxin required was somewhat greater than that needed with ribosomes. Digestion of homopolynucleotides with alpha-sarcin indicated that the protein is specific for purines. When [32P]5 S rRNA was the substrate, alpha-sarcin cleaved on the 3' side of purines in both single- and double-stranded regions of the molecule. The results suggest that the unusual specificity of alpha-sarcin, in that it cleaves only one of more than 7000 phosphodiester bonds in the ribosome, is a property both of the cytotoxin and of the ribosome.


Electrocardiographic changes simulating acute myocardial infarction or ischemia associated with combination chemotherapy with etoposide, cisplatin, and 5-fluorouracil.
Three cases of cardiotoxicity manifested by chest pain, tachycardia, respiratory distress, and electrocardiographic changes simulating acute myocardial infarction or ischemia were observed during the course of combination chemotherapy with etoposide, cisplatin, and continuous infusion of 5-fluorouracil in patients with advanced non-small cell lung cancer. There was no cardiac enzyme elevation. A similar but rare clinical syndrome has been described in association with 5-fluorouracil infusion as a single agent or in combination with other chemotherapeutic agents. We describe the cases and review their possible pathogeneses and clinical implications.


The environmental impact of the sugar industry waste in Sudan.
The purpose of this study was to investigate the impact of Sudanese sugar manufacturing waste on the communities surrounding the industries. The study employed a cross-sectional survey in which 311 respondents living in factory areas. The selected sugar industries included Kenana, Guneid, Halfa, Sinnar, Assalaya, and White Nile. Data were analyzed using SPSS version 19. Descriptive statistics, nonparametric statistics, and logistic regression were employed. The results showed that wastewater discharge has a significant (P < 0.05) effect on community health. Respondents indicated that the waste creates an ideal environment for parasites to reproduce, off-odors to develop, and ultimately contamination of water. A multinomial logistic regression model showed that wastewater (i.e., off-odors and mosquitoes) have significant (P 0.05) influences on causing health risks (i.e., malaria) to people living around sugar factories. The study also revealed that the lack of sugar industry wastewater management has significantly affected crop and animal production. The suspended particles and bagasse fly were significant (P 0.05) in causing eye and respiratory system diseases in the region. Health services provided by the industries significantly (P = 0.05) impacted community satisfaction. In this regard, the study designed a framework for enhanced handling the industrial waste to be adopted by the Sudanese sugar industry decision-makers. A framework was developed to reduce the impact of waste to the lowest possible level by improving management strategies sufficiently to minimize its impact.


Managing Right Ventricular Failure After Left Ventricular Assist Device Implant at a Destination Therapy Center.
Although left ventricular assist device (LVAD) implant is associated with an increased survival in patients with end-stage heart failure, severe right ventricular failure requiring a right ventricular assist device (RVAD) placement is associated with increased short-term morbidity and mortality. Patients not eligible for transplant have limited options, which may impact decision-making and outcomes at nontransplant centers. We conducted a retrospective review of all LVAD implants at our nontransplant center. Primary stratification was by the need for a postoperative RVAD implant. The primary outcome was survival. The Cox proportional hazards regression modeling was used to further evaluate mortality. From 2017 to 2022, 128 patients underwent a primary LVAD implant and 24 (18.75%) required a perioperative RVAD placement. RVAD implant was associated with increased operative mortality (1.92% vs 33.33%, p <0.01) and decreased 1-year (91.29% vs 60.60%, p <0.01) and 2-year survival (84.05% vs 36.36%, p <0.01). However, in patients who survived their index hospitalization, 1-year (93.00% vs 91.67%, p = 0.78) and 2-year (86.16% vs 55.00%, p = 0.10) mortality were similar. On multivariable analysis, the need for a RVAD was associated with an increased hazard of 1-year (5.60 [1.96 to 16.01], p <0.01) and 2-year (5.17 [2.01 to 13.28], p <0.01) mortality. In conclusion, our series from a nontransplant center suggests that patients who survive the implant have acceptable short-term survival, even if they do not have a transplant option; thus, carefully selected patients with biventricular failure may benefit from an LVAD implant, even if an RVAD is needed.


Performance analyses of effective rainfall estimation methods for accurate quantification of agricultural water footprint.
Water footprint (WF) assessments have become a significant tool for the sustainable management in recent years. Effective rainfall (Peff) is a critical indicator for characterizing soil moisture (green water, WFgreen) and calculating irrigation requirements (blue water, WFblue). However, majority of the water footprint analyses employ empirical or numerical models to predict Peff, and the number of studies for experimental validation of these models are quite insufficient. The main scope of this study is to test the performance of commonly used Peff estimation models in relation to the soil water balance (SWB) of an experimental site. Accordingly, the daily and monthly soil water budget is estimated from a maize field which is characterized as semi-arid land with continental climate (Ankara, Turkey), equipped with moisture sensors. Then, Peff, WFgreen, and WFblue parameters are calculated using FP, US-BR, USDA-SCS, FAO/AGLW, CROPWAT, and SuET methods and compared with SWB method. Employed models were highly variable. CROPWAT and US-BR predictions were the most accurate. In majority of months, the CROPWAT method estimated the Peff with a maximum deviation of 5% from the SWB method. In addition, the CROPWAT method predicted blue WF with an error less than 1%. The widely utilized USDA-SCS approach did not produce expected results. The FAO-AGLW method provided the lowest performance for each parameter. We also find that the errors in estimating Peff in semi-arid conditions cause green and blue WF outputs to be quite less accurate than the dry and humid cases. This study provides one of the most detailed assessments about the impact of effective rainfall on the blue and green WF results with high temporal resolution. The findings of this study are important for the accuracy and performance of the formulae used in Peff estimations and to develop more precise blue and green WF analyses in the future.


Lipopolysaccharide increases gamma-aminobutyric acid synthesis in medial preoptic neurones in association with inhibition of steroid-induced luteinising hormone surge in female rats.
Lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, inhibits gonadotrophin secretion and ovulation in female mammals. The present study was undertaken to examine whether gamma-aminobutyric acid (GABA)-synthesising neurones in the medial preoptic area (mPOA) may be involved in the inhibition by LPS of progesterone-induced luteinising hormone (LH) surge in ovariectomised oestrogen-primed rats. An intravenous injection of LPS (10 microg) at noon significantly increased the content of glutamic acid decarboxylase 67 (GAD67), a GABA-synthesising enzyme, in brain tissues including the mPOA. LPS treatment also significantly increased the number of detectable GAD67-immunoreactive (ir) as well as GABA-ir cells in the mPOA, compared to control rats. The same LPS challenge completely eliminated the steroid-induced LH surge, which was normally induced in control rats in the afternoon. A local injection of muscimol (100 ng), a GABA(A) receptor agonist, into the mPOA also significantly attenuated the LH surge, mimicking the effect of LPS. These results suggest that LPS stimulates GABA synthesis in preoptic neurones, which in turn inhibit the LH surge in female rats. The results also support the hypothesis that diminution of the GABAergic suppressive activity in the mPOA permits the LH surge to be induced.


Laboratory evaluation of two point-of-care detection systems for early and accurate detection of influenza viruses in the Lao People's Democratic Republic.
We evaluated molecular-based point-of-care influenza virus detection systems in a laboratory prior to a field evaluation of on-site specimen testing. The performance characteristics of 1) insulated isothermal polymerase chain reaction (PCR) on a POCKIT™ device and 2) real-time reverse transcription-PCR (rRT-PCR) on a MyGo Mini™ device were evaluated using human clinical specimens, beta-propiolactone-inactivated influenza viruses, and RNA controls. The rRT-PCR carried out on a CXF-96™ real-time detection system was used as a gold standard for comparison. Both systems demonstrated 100% sensitivity and specificity and test results were in 100% agreement with the gold standard. POCKIT™ only correctly identified influenza A (M gene) in clinical specimens due to the unavailability of typing and subtyping reagents for human influenza viruses, while MyGo Mini™ had either a one log higher or the same sensitivity in detecting influenza viruses in clinical specimens compared to the gold standard. For inactivated viruses and/or viral RNA, the analytic sensitivity of POCKIT™ was shown to be comparable to, or more sensitive, than the gold standard. The analytic sensitivity of MyGo Mini™ had mixed results depending on the types and subtypes of influenza viruses. The performance of the two systems in a laboratory is promising and supports further evaluation in field settings.


Cellular toxicity of gentamicin.
Subconjunctival injections of gentamicin induced a lysosomal storage process within the conjunctival fibroblasts in rats, rabbits, and humans. Under electron microscopy, the accumulated substance was composed of a granular material and pleomorphic lamellar structures, corresponding to the presence of complex lipids. In animals, the other ocular tissues as well as the cells reached through the bloodstream remained unaffected, except the proximal convoluted tubules of the kidneys, where important lesions were evident. Although human kidneys were not examined in our study, we believe they might present similar alterations.


An expeditious and precise method for diameter reduction of venous aneurysm causing arteriovenous fistula steal syndrome.
Clinically significant dialysis access steal syndrome occurs in 1% to 8% of patients. In the present report, we describe an innovative, hybrid option for venoplasty of a cephalic vein aneurysm using a vascular staple device in conjunction with a 6-mm, endovascular balloon placed a few centimeters distal to the brachial artery anastomosis in a 61-year-old man with stage 3 dialysis access steal syndrome secondary to overwhelming venous outflow. The patient experienced immediate postoperative symptom relief. The arteriovenous fistula was immediately accessible for dialysis, circumventing the need for a temporary dialysis catheter. The arteriovenous fistula was functional at 12 months of follow-up.


Sex-Specific Physiological Responses to Ultramarathon.
Despite a growing body of literature on the physiological responses to ultramarathon, there is a paucity of data in females. This study assessed the female physiological response to ultramarathon and compared the frequency of perturbations to a group of race- and time-matched males. Data were collected from 53 contestants of an ultramarathon trail race at the Ultra-Trail du Mont-Blanc (UTMB®) in 2018/19. Before and within 2 h of the finish, participants underwent physiological assessments, including blood sampling for biomarkers (creatine kinase-MB isoenzyme [CK-MB], cardiac troponin I [cTnI], brain natriuretic peptide [BNP], and creatinine [Cr]), pulmonary function testing (spirometry, exhaled NO, diffusing capacities, and mouth pressures), and transthoracic ultrasound (lung comet tails, cardiac function). Data from eight female finishers (age = 36.6 ± 6.9 yr; finish time = 30:57 ± 11:36 h:min) were compared with a group of eight time-matched males (age = 40.3 ± 8.3 yr; finish time = 30:46 ± 10:32 h:min). Females exhibited significant pre- to postrace increases in BNP (25.8 ± 14.6 vs 140.9 ± 102.7 pg·mL -1 ; P = 0.007) and CK-MB (3.3 ± 2.4 vs 74.6 ± 49.6 IU·L -1 ; P = 0.005), whereas males exhibited significant pre- to postrace increases in BNP (26.6 ± 17.5 vs 96.4 ± 51.9 pg·mL -1 ; P = 0.002), CK-MB (7.2 ± 3.9 vs 108.8 ± 37.4 IU·L -1 ; P = 0.002), and Cr (1.06 ± 0.19 vs 1.23 ± 0.24 mg·dL -1 ; P = 0.028). Lung function declined in both groups, but males exhibited additional reductions in lung diffusing capacities (DL CO = 34.4 ± 5.7 vs 29.2 ± 6.9 mL⋅min -1 ⋅mm Hg -1 , P = 0.004; DL NO = 179.1 ± 26.2 vs 152.8 ± 33.4 mL⋅min -1 ⋅mm Hg -1 , P = 0.002) and pulmonary capillary blood volumes (77.4 ± 16.7 vs 57.3 ± 16.1 mL; P = 0.002). Males, but not females, exhibited evidence of mild postrace pulmonary edema. Pooled effect sizes for within-group pre- to postrace changes, for all variables, were generally larger in males versus females ( d = 0.86 vs 0.63). Ultramarathon negatively affects a range of physiological functions but generally evokes more frequent perturbations, with larger effect sizes, in males compared to females with similar race performances.


Comparison of carotid artery ultrasound and manual method for pulse check in cardiopulmonary resuscitation.
The success of the manual pulse check method frequently employed during cardiopulmonary resuscitation (CPR) is controversial due to its subjective, patient- and operator-dependent, and time-consuming nature. Carotid ultrasound (c-USG) has recently emerged as an alternative, although there are still insufficient studies on the subject. The purpose of the present study was to compare the success of the manual and c-USG pulse check methods during CPR. This prospective observational study was conducted in the critical care area of a university hospital emergency medicine clinic. Pulse checks in patients with non-traumatic cardiopulmonary arrest (CPA) undergoing CPR were performed using the c-USG method from one carotid artery and the manual method from the other. The gold standard in the decision regarding return of spontaneous circulation (ROSC) was the clinical judgment made using the rhythm on the monitor, manual femoral pulse check, end tidal carbon dioxide (ETCO2), and cardiac USG instruments. The success in predicting ROSC and measurement times of the manual and c-USG methods were compared. The success of both methods was calculated as sensitivity and specificity, and the clinical significance of the difference between the methods' sensitivity and specificity was evaluated Newcombe's method. A total of 568 pulse measurements were performed on 49 CPA cases using both c-USG and the manual method. The manual method exhibited 80% sensitivity and 91% specificity in predicting ROSC (+PV: 35%, -PV: 64%), while c-USG exhibited 100% sensitivity and 98% specificity (+PV: 84%, -PV: 100%). The difference in sensitivities between the c-USG and manual methods was -0.0704 (95% CI: -0.0965; -0.0466), and the difference between their specificities was 0.0106 (95% CI: 0.0006; 0.0222). The difference between the specificities and sensitivities was statistically significant at analysis performed adopting the clinical judgment of the team leader using multiple instruments as the gold standard. The manual method yielded an ROSC decision in 3 ± 0.17 s and c-USG in 2.8 ± 0.15 s, the difference being statistically significant. According to the results of this study, the pulse check method with c-USG may be superior to the manual method in terms of fast and accurate decision making in CPR.


Rivaroxaban in patients with abdominal aortic aneurysm and high-sensitivity C-reactive protein elevation (BANBOO): study protocol for a randomized, controlled trial.
Abdominal aortic aneurysm (AAA) is a fatal disease due to the tendency to rupture. The drug treatment for small AAA without surgical indications has been controversial. Previous studies showed that high-sensitivity C-reactive protein (hs-CRP) had become a potential biomarker of the disease, and the anti-inflammatory effect of rivaroxaban for AAA had been well established. Thus, we hypothesized that rivaroxaban could control the progression of AAA in patients with hs-CRP elevation. The study is a prospective, open-label, randomized, controlled clinical trial. Sixty subjects are recruited from the General Hospital of Northern Theatre Command of China. Subjects are randomly assigned (1:1) to the intervention arm (rivaroxaban) or control arm (aspirin). The primary efficacy outcome is the level of serum hs-CRP at 6 months. The secondary outcomes include imaging examination (the maximal diameter of AAA, the maximal thickness of mural thrombus, and the length of aneurysm), major adverse cardiovascular and cerebrovascular events (MACCE, including AAA transformation, non-fatal myocardial infarction, acute congestive heart failure, stent thrombosis, ischemia-driven target vessel revascularization, vascular amputation, stroke, cardiovascular death, and all-cause death), and other laboratory tests (troponin T, interleukin 6, D-dimer, and coagulation function). The BANBOO trial tested the effect of rivaroxaban on the progression of AAA in patients with elevated Hs-CRP for the first time. ChiCTR2100051990, ClinicalTrials.gov, registered on 12 October 2021.


Preparing nursing professionals fit for the evolving healthcare landscape.
The revised Nursing and Midwifery Council education curriculum, which came into force in January, has the potential to revolutionise nursing, says Barry Hill, Senior Lecturer, Northumbria University ( email@example.com ).


Inferring protein domain interactions from databases of interacting proteins.
We describe domain pair exclusion analysis (DPEA), a method for inferring domain interactions from databases of interacting proteins. DPEA features a log odds score, Eij, reflecting confidence that domains i and j interact. We analyzed 177,233 potential domain interactions underlying 26,032 protein interactions. In total, 3,005 high-confidence domain interactions were inferred, and were evaluated using known domain interactions in the Protein Data Bank. DPEA may prove useful in guiding experiment-based discovery of previously unrecognized domain interactions.


Platelet changes after a saturated fat meal and their prevention by Dazmegrel, a thromboxane synthetase inhibitor.
A saturated fat meal was given to 10 normal males both before and after pretreatment with UK38,485, a thromboxane synthetase inhibitor (Dazmegrel, Pfizer Central Research, Sandwich, Kent, United Kingdom). Following the fat meal at 2 and 4 hr there was laboratory evidence of platelet activation. Dazmegrel lowered baseline platelet activity and lessened platelet activation following the fat meal. This drug should be investigated further as a potential antithrombotic agent.


Future prospects for implantable devices for atrial defibrillation.
The success of the implantable cardioverter defibrillator (ICD) led to the concept of a device that would terminate atrial fibrillation (AF) using an implantable device. Implantable devices for AF are undergoing rapid evolution. Currently used devices combine pacing and cardioversion therapies to prevent and to treat AE Recent studies have shown that these devices are safe and can decrease the incidence of AF and improve quality of life significantly. Implantable devices for atrial defibrillation are likely to have an increasing role in the near future, particularly when they are used in combination with ICD and cardiac resynchronization therapy in which AF is both common and its termination is clinically beneficial.


The brain in experimental portal-systemic encephalopathy. II. Water and electrolyte changes.
The water content and amounts of sodium, potassium and chloride were measured in the brains of normal rats, rats with PCA, normal rats fed ammoniated cationic exchange resin, and rats with PCA fed the resin. Plasma electrolytes and ammonia levels were also measured, and sodium and chloride spaces were calculated. Rats with PCA showed increased water content, sodium space and chloride space in the brainstem compared to controls. Rats with PCA fed ammoniated resin showed increased chloride content and Na+:K+ ratio in the brainstem, and an increased chloride space in the brainstem. In these rats the chloride spaces in the cerebrum and cerebellum exceeded the sodium spaces. It is concluded that high circulating ammonia levels can in vivo produce ionic shifts which may interfere with nervous function. It is also concluded that increased cytoplasmic osmolarity produced by ammonium ion-induced stimulation of (Na+ + Ka+) ATPase may result in the appearance of swollen astrocytes in conventional electron micrographs.


Focal adhesions are foci for tyrosine-based signal transduction via GIV/Girdin and G proteins.
GIV/Girdin is a multimodular signal transducer and a bona fide metastasis-related protein. As a guanidine exchange factor (GEF), GIV modulates signals initiated by growth factors (chemical signals) by activating the G protein Gαi. Here we report that mechanical signals triggered by the extracellular matrix (ECM) also converge on GIV-GEF via β1 integrins and that focal adhesions (FAs) serve as the major hubs for mechanochemical signaling via GIV. GIV interacts with focal adhesion kinase (FAK) and ligand-activated β1 integrins. Phosphorylation of GIV by FAK enhances PI3K-Akt signaling, the integrity of FAs, increases cell-ECM adhesion, and triggers ECM-induced cell motility. Activation of Gαi by GIV-GEF further potentiates FAK-GIV-PI3K-Akt signaling at the FAs. Spatially restricted signaling via tyrosine phosphorylated GIV at the FAs is enhanced during cancer metastasis. Thus GIV-GEF serves as a unifying platform for integration and amplification of adhesion (mechanical) and growth factor (chemical) signals during cancer progression.


Transcriptomic analysis of gene expression of menaquinone-7 in Bacillus subtilis natto toward different oxygen supply.
Menaquinone-7 (MK-7) is an important kind of vitamin K2 which plays significant roles in the treatment of coagulation and osteoporosis, and prevention of cardiovascular disease. This work was purposed to study the differences of gene expression at different oxygen supply conditions in Bacillus natto. The differences of fermentation characteristics, gene expression related to MK-7 biosynthesis, spore and biofilm formation were analyzed. The yield of MK-7 increased by two fold under high oxygen supply condition of 200 rpm. Further transcriptome analysis indicated that most of the enzymes in MK-7 biosynthesis pathway were also up-regulated. Moreover, glycerol kinase, fructose-bisphosphate aldolase and phosphofructokinase in glycolysis pathway were all up-regulated indicating that high oxygen supply can increase the consumption of substrate glycerol. Meanwhile, menD, encoded the rate-limiting enzyme in the MK pathway, was obviously up-regulated by 3.49-fold while most of the enzymes related to spore formation were down regulated at 200 rpm. Besides, superoxide dismutase (SOD2), catalase (CAT), hydroperoxide reductase (AhpF) and DNA-binding protein MrgA in the antioxidant defense system were up-regulated, while superoxide dismutase (SOD1) and glutathione peroxidase (GSH-Px) were down-regulated. These results could contribute to a better understanding for the effect of oxygen on the MK-7 production in Bacillus natto, and further analyze the molecular regulation mechanism of MK-7 biosynthesis.


Nerve growth factor with fibrin glue in end-to-side nerve repair in rats.
To determine the effects of end-to-side nerve repair performed only with fibrin glue containing nerve growth in rats. Seventy two Wistar rats were divided into six equal groups: group A was not submitted to nerve section; group B was submitted to nerve fibular section only. The others groups had the nerve fibular sectioned and then repaired in the lateral surface of an intact tibial nerve, with different procedures: group C: ETS with sutures; group D: ETS with sutures and NGF; group E: ETS with FG only; group F: ETS with FG containing NGF. The motor function was accompanied and the tibial muscle mass, the number and diameter of muscular fibers and regenerated axons were measured. All the analyzed variables did not show any differences among the four operated groups (p>0.05), which were statistically superior to group B (p<0.05), but inferior to group A (p>0.05). The end-to-side nerve repair presented the same recovery pattern, independent from the repair used, showing that the addition of nerve growth factor in fibrin glue was not enough for the results potentiating.


Deliberate self-harm before psychiatric admission and risk of suicide: survival in a Danish national cohort.
Psychiatric illness and deliberate self-harm (DSH) are major risk factors of suicide. In largely 15% of psychiatric admissions in Denmark, the patient had an episode of DSH within the last year before admission. This study examined the survival and predictors of suicide in a suicidal high-risk cohort consisting of hospitalized psychiatric patients with recent DSH. This national prospective register-based study examined all hospitalized psychiatric patients who self-harmed within a year before admission. All admitted patients, in the time period 1998-2006, were followed and survival analyses techniques were used to identify predictors of suicide. The study population consisted of 17,257 patients; 520 (3%) died by suicide during follow-up; 50% of the suicides occurred within a year from the index admission. A rate of 1,645 suicides per 100,000 person-years in the first year after psychiatric admission was found. Adjusted analyses showed that a higher degree of education, having DSH within a month before psychiatric admission and contact with a private psychiatrist increased the risk of suicide. Psychiatric hospitalized patients with recent DSH revealed high suicide rates, even during hospitalization. When discharging psychiatric patients with recent DSH careful arrangement of follow-up treatment in the outpatient setting is recommendable.


Spatial distribution of polycyclic aromatic hydrocarbons in the Philippine Sea, Western Pacific and the impact factors analysis.
Knowing the polycyclic aromatic hydrocarbons (PAHs) pollution properties in ocean is highly needed to protect the open sea. In July to August of 2020, twenty surface water samples were obtained from the East China Sea to the Philippine Sea. The ranges of Σ15PAHs concentrations were 3.188-5.29 ng L-1 in dissolved phase, 0.455-1.305 ng L-1 in particulate phase in the Philippine Sea. 3, 4-Ring PAHs were the most abundant PAHs. Their spatial differences in dissolved phase were mainly caused by human activities, the summer monsoon from the Philippine Islands and the Northern Equatorial Current, and the Kuroshio Current and Subtropical Countercurrent. The source analysis showed that PAHs in surface water in the Philippine Sea may come from coal combustion. It is the first time to analyze the occurrence and distribution of PAHs in the Philippine Sea.


Familial clustering of rheumatoid arthritis with other autoimmune diseases.
Previous studies have shown that rheumatoid arthritis aggregates within families. However, no formal genetic analysis of rheumatoid arthritis in pedigrees together with other autoimmune diseases has been reported. We hypothesized that there are genetic factors in common in rheumatoid arthritis and other autoimmune diseases. Results of odds-ratio regression and complex segregation analysis in a sample of 43 Caucasian pedigrees ascertained through a rheumatoid arthritis proband or matched control proband, revealed a very strong genetic influence on the occurrence of both rheumatoid arthritis and other autoimmune diseases. In an analysis of rheumatoid arthritis alone, only one inter-class measure, parent-sibling, resulted in positive evidence of aggregation. However, three inter-class measures (parent-sibling, sibling-offspring, and parent-offspring pairs) showed significant evidence of familial aggregation with odds-ratio regression analysis of rheumatoid arthritis together with all other autoimmune diseases. Segregation analysis of rheumatoid arthritis alone revealed that the mixed model, including both polygenic and major gene components, was the most parsimonious. Similarly, segregation analysis of rheumatoid arthritis together with other autoimmune diseases revealed that a mixed model fitted the data significantly better than either major gene or polygenic models. These results were consistent with a previous study which concluded that several genes, including one with a major effect, is responsible for rheumatoid arthritis in families. Our data showed that this conclusion also held when the phenotype was defined as rheumatoid arthritis and/or other autoimmune diseases, suggesting that several major autoimmune diseases result from pleiotropic effects of a single major gene on a polygenic background.


Effects of a Mask on Breathing Impairment During a Fencing Assault: A Case Series Study.
Fencers often complain of progressive difficulty in breathing during matches, which is generally attributed to restricted air, light and heat circulation from wearing a mask. Physiologically, the nasal structure generates airflow resistance that can reach -50% of the total respiratory resistance. This study aims to investigate the presence of nasal obstruction in fencers and the relationship with the use of mask. An observational study on 40 fencers (18 males, 22 females) was conducted. Fencers perform a usual assault, wearing the mask and standardized physical exercises (running, sprints and obstacles) without the mask. ENT examination with a nasal flexible fiberscope, Anterior Active Rhinomanometry (AAR) and Peak Nasal Inspiratory Flow (PNIF) measurement before and after physical activity with or without the mask was recorded. Before physical exercise, the total nasal airway resistance mean value for AAR was 0.33 ± 0.17 Pa/cm(3)/s at 150 Pa. After a match with the mask, the mean value was 0.28 ± 0.16 Pa/cm(3)/s. After normal physical exercises without mask, the mean value was 0.24 ± 0.15 Pa/cm(3)/s. Using t tests, statistically significant difference between nasal resistance before and after physical activity (P < 0.05) was observed, but no significant difference in nasal resistance between the basal value and that taken after a match wearing the masks (P = 0.1265). PNIF values significantly increase with exercise (P < 0.05). Our study shows that wearing the mask causes increased breathing impairment in fencers, when compared with similar physical activity without the mask.


Can we really save 5 million lives?
Hospitals leapt at the challenge to save 100,000 lives through evidence-based medicine. Now that the goal is dramatically higher, how are hospitals responding?


Association of air pollutants and meteorological factors with tuberculosis: a national multicenter ecological study in China.
The impact of weather variability and air pollutants on tuberculosis (TB) has been a research hotspot. Previous studies have mostly been limited to a certain area or with a small sample size of cases, and multi-scale systematic studies are lacking. In this study, 14,816,329 TB cases were collected from 31 provinces in China between 2004 and 2018 to estimate the association between TB risk and meteorological factors and air pollutants using a two-stage time-series analysis. The impact and lagged time of meteorological factors and air pollutants on TB risk varied greatly in different provinces and regions. Overall cumulative exposure-response summary associations across 31 provinces suggested that high monthly mean relative humidity (RH) (66.8-82.4%, percentile56-100 (P56-100)), rainfall (316.5-331.1 mm, P96-100), PM2.5 exposure concentration (93.3-145.0 μg/m3, P58-100), and low monthly mean wind speed (1.6-2.1 m/s, P0-38) increased the risk of TB incidence, with a relative risk (RR) of 1.10 (95% CI: 1.04-1.16), 1.10 (95% CI: 1.03-1.16), 2.08 (95% CI: 1.18-3.65), and 2.06 (95% CI: 1.27-3.33), and attributable risk percent (AR%) of 9%, 9%, 52%, and 51%, respectively. Conversely, high monthly average wind speed (2.3-2.9 m/s, P54-100) and mean temperature (20.2-25.3 °C, P79-96), and low monthly average rainfall (2.4-25.2 mm, P0-7) and concentration of SO2 (8.1-21.2 μg/m3, P0-16) exposure decreased the risk of TB incidence, with an overall cumulative RR of 0.92 (95% CI: 0.87-0.98), 0.74 (95% CI: 0.59-0.94), 0.87 (95% CI: 0.79-0.95), and 0.72 (95% CI: 0.56-0.93), respectively. Our study provided insights into future planning of public health interventions for TB.


Primary care management post gestational diabetes in Australia.
Women with a history of gestational diabetes (GD) have a high risk of developing diabetes and subsequent cardiovascular disease (CVD). To assess whether diabetes screening and CVD risk screening occurred in general practice (GP) among postpartum women with GD. This is a retrospective study of clinical record data of women with GD, under active GP management, from the MedicineInsight programme, run by Australia's National Prescribing Service MedicineWise, with GP sites located in Australia from January 2015 to March 2021. Documentation of screening for diabetes, assessment of lipids and measurement of blood pressure (BP) was assessed using proportions and mixed-effects logistic regression with a log follow-up time offset. There were 10 413 women, with a mean age of 37.9 years (standard deviation, 7.6), from 406 clinics with a mean follow-up of 4.6 years (interquartile range, 1.8-6.2 years) A total of 29.41% (3062/10 413; 95% confidence interval [CI], 28.53-30.28) had not been assessed for diabetes, 37.40% (3894/10 413; 95% CI, 36.47-38.32) were not assessed for lipids and 2.19% (228/10 413; 95% CI, 1.91-2.47) had no BP documented. In total, 51.82% (5396/10 413; 95% CI, 50.86-52.78) were screened for all three (diabetes + lipids + BP) at least once. Obesity, comorbidities and dyslipidaemia were associated with increased likelihood of screening. New diabetes diagnosis was documented in 5.73% (597/10 413; 95% CI, 5.29-6.18) of the cohort. Screening for diabetes and hyperlipidaemia was suboptimal in this high-risk cohort of women with prior GD. Improved messaging that women with a GD diagnosis are at high cardiovascular risk may improve subsequent screening.


Nutritional elements in U.S. diets: results from the Total Diet Study, 1982 to 1986.
Through the Food and Drug Administration's Total Diet Study, the levels of 11 nutritional elements (sodium, potassium, calcium, phosphorus, magnesium, iron, zinc, copper, manganese, selenium, and iodine) in the diets of eight age-sex groups were determined for the 4 years between 1982 and 1986. The 234 Total Diet Study foods, which are representative of the U.S. food supply, were purchased, prepared for consumption, and analyzed for the elements four times each year. The results were combined with national food consumption data to estimate intakes for 6- to 11-month-old infants, 2-year-old children, 14- to 16-year-old boys and girls, 25- to 30-year-old men and women, and 60- to 65-year-old men and women. Six elements (calcium, magnesium, iron, zinc, copper, and manganese) were low (less than 80% of the Recommended Dietary Allowance or below the low end of the Estimated Safe and Adequate Daily Dietary Intake range) for three or more of the age-sex groups. Six elements were of concern for teenage girls and adult women, five for older women, three for 2-year-old children, two for teenage boys and older men, and only one for infants and adult men. Sodium levels (which did not include discretionary salt) were elevated for 2-year-old children and teenage boys, and iodine was elevated for all age-sex groups. A significant trend was noted only for iodine, the intake of which decreased during the 4-year period.(ABSTRACT TRUNCATED AT 250 WORDS)


Short sequence repeats of the intergenic spacer regions of ribosomal RNA genes in Malassezia globosa and Malassezia restricta colonizing the scalps of male individuals with and without androgenetic alopecia.
We analyzed the short sequence repeats (SSRs) of the intergenic spacer (IGS) region 1 of the ribosomal RNA genes in Malassezia globosa and Malassezia restricta, which predominantly colonize the scalp in androgenetic alopecia (AGA). No AGA-specific SSRs were found in the M. globosa IGS region, whereas a (CT)6 :(AT)8 SSR was predominantly detected in the M. restricta IGS region in the AGA group. Malassezia colonization was higher in the scalps of patients with M. restricta (CT)6 :(AT)8 SSRs than in the scalps of patients without M. restricta (CT)6 :(AT)8 SSRs. These observations suggest that this specific SSR type in M. restricta is involved in the development or exacerbation of AGA.


Racial/Ethnic Differences and Trends in Pathologic Complete Response Following Neoadjuvant Chemotherapy for Breast Cancer.
The purpose of this study was to evaluate nationwide trends in pathologic complete response (pCR) and its racial variations for breast cancer. The National Cancer Database was queried for women from 2010 to 2017 with non-metastatic breast cancer who underwent neoadjuvant chemotherapy. The primary endpoints, pCR and overall survival, were evaluated using Cochran-Armitage test, logistic, and Cox regression multivariable analyses. A total of 104,161 women were analyzed. Overall, pCR improved from 2010 to 2017 (15.1% to 27.2%, trend p < 0.001). Compared to non-Hispanic White (NHW) women, Hispanic White (HW) women were more likely to have pCR for hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-positive tumors (adjusted odds ratio (aOR) 1.29, 95% confidence interval (CI) 1.08-1.53, p = 0.005). Black women were less likely to have pCR for HR-HER2+ tumors (aOR 0.81, 95% CI 0.73-0.89, p < 0.001) and triple negative (aOR 0.82, 95% CI 0.77-0.87, p < 0.001) tumors, but more likely for HR+HER2- tumors (aOR 1.13, 95% CI 1.03-1.24, p = 0.009). Among patients who achieved pCR, Asian or Pacific Islander (API) women were associated with better survival (adjusted hazards ratio (aHR) 0.52, 95% CI 0.33-0.82, p = 0.005) than NHW women. Despite positive trends in pCR rates, the likelihood of pCR and survival outcomes may be intricately dependent on racial/ethnic groups and tumor receptor subtypes.


Antigen binding by conformational selection in near-germline antibodies.
Conformational flexibility in antibody-combining sites has been hypothesized to facilitate polyspecificity toward multiple unique epitopes and enable the limited germline repertoire to match an overwhelming diversity of potential antigens; however, elucidating the mechanisms of antigen recognition by flexible antibodies has been understandably challenging. Here, multiple liganded and unliganded crystal structures of the near-germline anticarbohydrate antibodies S25-2 and S25-39 are reported, which reveal an unprecedented diversity of complementarity-determining region H3 conformations in apparent equilibrium. These structures demonstrate that at least some germline or near-germline antibodies are flexible entities sensitive to their chemical environments, with conformational selection available as an evolved mechanism that preserves the inherited ability to recognize common pathogens while remaining adaptable to new threats.


A method of controlled closure: the use of Ligaclips in the delayed primary closure of flaps.
BACKGROUND AND PURPOSES OF THE STUDY: Achieving primary closure of a flap may not always be possible initially. Current controlled closure techniques exert uniform pressure across a wound, which is unsuitable for a flap, as it can induce ischaemia in vulnerable areas. Using Ligaclips (Ethicon Inc., Somerville, NJ, USA) to secure tissue advancement along mattress sutures offers both the ease of expansion, like running sutures, and the ability to moderate tension in discrete areas, like interrupted sutures. The two cases here highlight variations of how this technique can be applied to close wounds boarded by vulnerable tissues such as flaps. We conclude that the use of Ligaclips in conjunction with mattress sutures in the controlled closure of defects around flaps is simple and fast, enabling greater control over the forces exerted over discrete areas, minimising the risk of compromising vulnerable tissues.


[Thoracic manifestations of Behcet's disease].
Behcet's disease (BD) is a multisystemic vasculitis involving arteries and veins of all sizes. While joint and dermatological manifestations are the most common features of BD and are associated with a good prognosis; vascular involvement, remains the principal cause of death. Arterial manifestations occur in 5-10% of cases and manifest as occlusion/thrombosis or aneurysms. Arterial aneurysms are likely multiple and the most common sites are pulmonary arteries, aorta and arteries of lower limbs. Parenchymal involvement is less frequent and may manifest as consolidation or nodules, which may evolve to excavation. Aneurysms may occur at the sites of arterial puncture; then, non-traumatic techniques are favored. Patients with arterial manifestations may present with fever and increased inflammatory markers. Artery damage is rare, serious, and may result in massive hemoptysis. The prognosis of pulmonary artery aneurysms is severe (mortality estimated up to 26%) but has been improved by earlier diagnosis and the introduction of immunosuppressants. Treatment of severe arterial manifestations is based on high-dose corticosteroids along with cyclophosphamide or anti-TNF antagonists. Anticoagulation could be added to immunosuppressants in case of venous thrombosis if a coexisting pulmonary aneurysm is ruled out. Endovascular treatment should be performed in case of severe symptomatic pulmonary aneurysms, along with an adequate medical management. Long-term maintenance therapy of these severe forms is of paramount importance because of relapse risk (40% at five years).


Response of lymphocytes from Fanconi's anemia patients and their heterozygous relatives to 8-methoxy-psoralene in a cloning survival test system.
Five homozygous patients with Fanconi's anemia and nine heterozygous relatives were studied for mutagen sensitivity by a new method. Lymphocyte cloning survival after treatment with several doses of the cross linking substance 8-methoxy-psoralene and exhaustive activation with UVa-light was used for precise measurement of the dose-response. Sensitivity of the homozygous lymphocytes was greatly increased; the degree of the cellular defects corresponded to the clinical course. In the two cases with highest sensitivity, the heterozygotes could be differentiated from normal probands by increased sensitivity, whereas this was not the case in three other families.


Depressed adolescents in a case-series were low in vitamin D and depression was ameliorated by vitamin D supplementation.
The relationship between depression in adolescents and vitamin D was studied in a case-series that included effects of vitamin D supplementation. Serum 25OH vitamin D (25OHD) levels in 54 Swedish depressed adolescents were investigated. Subjects with vitamin D deficiency were given vitamin D(3) over 3 months (n = 48). To evaluate well-being and symptoms related to depression and vitamin D status, the WHO-5 well-being scale, the Mood and Feelings Questionnaire (MFQ-S) and a vitamin D deficiency scale were used. Mean serum 25OHD in the depressed adolescents was 41 at baseline and 91 nmol/L (p < 0.001) after supplementation. Basal 25OHD levels correlated positively with well-being (p < 0.05). After vitamin D supplementation, well-being increased (p < 0.001) and there was a significant improvement in eight of the nine items in the vitamin D deficiency scale: depressed feeling (p < 0.001), irritability (p < 0.05), tiredness (p < 0.001), mood swings (p < 0.01), sleep difficulties (p < 0.01), weakness (p < 0.01), ability to concentrate (p < 0.05) and pain (p < 0.05). There was a significant amelioration of depression according to the MFQ-S (p < 0.05). This study showed low levels of vitamin D in 54 depressed adolescents, positive correlation between vitamin D and well-being, and improved symptoms related to depression and vitamin D deficiency after vitamin D supplementation.


Do cattle egrets gain information from conspecifics when foraging?
We examined whether individual cattle egrets (Bubulcus ibis) base their decisions of where to forage, and how long to stay in a patch, on the behavior of other flock members. Cattle egrets commonly forage in flocks associated with cattle and capture prey at higher rates when they do not share a cow with another egret. Foraging egrets provide cues of the location of prey and their success in capturing prey. Therefore, there is the possibility of information transfer between egrets in a flock. We predicted that egrets should only move to occupied patches when the resident was capturing enough prey that it is profitable for the invader to share the patch or take over the patch. However, egrets did not seem to decide where to forage based on neighbors' rates of energy intake, but rather on the presence or absence of conspecifics in a patch. We also predicted that an egret should remain in a patch until its rate of energy intake dropped to or below the average rate for other egrets within the flock. However, egrets that were foraging more efficiently than the average rate for the flock switched patches sooner than less efficient foragers. Egrets did not appear to increase foraging success by gaining information on patch quality from neighbors.


The Termination Phase in Protein Synthesis is not Obligatorily Followed by the RRF/EF-G-Dependent Recycling Phase.
It is general wisdom that termination of bacterial protein synthesis is obligatorily followed by recycling governed by the factors ribosomal recycling factor (RRF), EF-G, and IF3, where the ribosome dissociates into its subunits. In contrast, a recently described 70S-scanning mode of initiation holds that after termination, scanning of 70S can be triggered by fMet-tRNA to the initiation site of a downstream cistron. Here, we analyze the apparent conflict. We constructed a bicistronic mRNA coding for luciferases and showed with a highly resolved in vitro system that the expression of the second cistron did not at all depend on the presence of active RRF. An in vivo analysis cannot be performed in a straightforward way, since RRF is essential for viability and therefore, the RRF gene cannot be knocked out. However, we found an experimental window, where the RRF amount could be reduced to below 2.5%, and in this situation, the expression of the second cistron of a bicistronic luciferase mRNA was only moderately reduced. Both in vitro and in vivo results suggested that RRF-dependent recycling is not an obligatory step after termination, in agreement with the previous findings concerning 70S-scanning initiation. In this view, recycling after termination is a special case of the general RRF function, which happens whenever fMet-tRNA is not available for triggering 70S scanning.


TCDD-mediated suppression of naïve human B cell IgM secretion involves aryl hydrocarbon receptor-mediated reduction in STAT3 serine 727 phosphorylation and is restored by interferon-γ.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental contaminant formed as a byproduct in organic synthesis and burning of organic materials. TCDD has potent immunotoxic effects in B lymphocytes resulting in decreased cellular activation and suppressed IgM secretion following activation with CD40 ligand. Previous work from our lab demonstrated that TCDD treatment of naïve human B cells resulted in significant increases in the levels of the tyrosine phosphatase SHP-1, which corresponded with suppression of IgM secretion. STAT3 is a critical B cell transcription factor for B cell activation and secretion of immunoglobulins (Ig). STAT3 dimerizes and translocates to the nucleus following phosphorylation as a result of cytokine receptor signaling. We hypothesized that TCDD-mediated increases in SHP-1 could result in decreased STAT3 tyrosine phosphorylation. Interestingly, only modest changes in the levels of STAT3 tyrosine phosphorylation were observed. By contrast, TCDD significantly reduced levels of STAT3 serine phosphorylation as early as 12h post B cell activation. These results corresponded with decreased inhibitory phosphorylation of the serine specific phosphatase PP2a, which is regulated by SHP-1. Further, studies revealed that interferon gamma (IFNγ), which signals through the type II interferon receptor, can non-canonically induce STAT3 activation via Src kinase activity. Indeed, treatment of human B cells with IFNγ resulted in increased STAT3 serine phosphorylation and reversed TCDD-mediated suppression of the IgM response. Together, these data putatively identify a key event in the mechanism by which TCDD induces suppression of Ig secretion and demonstrate the potential of IFNγ as a means to reverse this effect in primary human B lymphocytes.


Transient sinus node dysfunction following sinus node artery occlusion due to radiofrequency catheter ablation of the septal superior vena cava-right atrium junction.
We performed catheter ablation to septal superior vena cava (SVC)-right atrium (RA) junction rapid firing in a 57-year-old man with paroxysmal atrial fibrillation. He later experienced transient sinus node dysfunction resulting from injury to the sinus node artery (SNA), which branched only from the proximal region of the left circumflex artery. The direction of the SNA should be considered during catheter ablation at the septal SVC-RA junction, especially if the sinus node is supplied by only one SNA from the right coronary artery or the left circumflex artery.


Precepting nurse practitioner students in the graduate nurse education demonstration: A cross-sectional analysis of the preceptor experience.
The Graduate Nurse Education (GNE) Demonstration seeks to increase the number of advanced practice registered nurses (APRNs) in clinical practice. With the overall increase in APRN programs and, particularly, enrollment in nurse practitioner (NP) programs, there is growing competition among students to secure quality clinical precepting experiences. This study describes NPs' and physicians' experiences with precepting APRN students within the Greater Philadelphia GNE Consortium. This was a cross-sectional descriptive survey of 1,021 NP and physician preceptors who provided clinical practicum experiences for at least one of the nine Greater Philadelphia GNE Consortium schools. Differences between NP and physician precepting experiences regarding the importance of various factors in their decisions to precept were explored. Both NP and physician preceptors provide clinical practicum experiences to APRN students because they enjoy doing so. However, they differ regarding what they find important in their decisions to precept such as having protected time to precept and educational opportunities. As universities work to recruit quality preceptors, they should consider tailoring their approach based on the preceptor's clinical role. In addition, schools located within the same region should consider streamlining administrative processes to form sustaining and productive clinical partnerships.


The role of the vagus nerve in appetite control: Implications for the pathogenesis of obesity.
The communication between the gut and the brain is important for the control of energy homeostasis. In response to food intake, enteroendocrine cells secrete gut hormones, which ultimately suppress appetite through centrally-mediated processes. Increasing evidence implicates the vagus nerve as an important conduit in transmitting these signals from the gastrointestinal tract to the brain. Studies have demonstrated that many of the gut hormones secreted from enteroendocrine cells signal through the vagus nerve, and the sensitivity of the vagus to these signals is regulated by feeding status. Furthermore, evidence suggests that a reduction in the ability of the vagus nerve to respond to the switch between a "fasted" and "fed" state, retaining sensitivity to orexigenic signals when fed or a reduced ability to respond to satiety hormones, may contribute to obesity. This review draws together the evidence that the vagus nerve is a crucial component of appetite regulation via the gut-brain axis, with a particular emphasis on experimental techniques and future developments.


Increased mortality in long-term intensive care patients with active cytomegalovirus infection.
To determine the prevalence and impact on patient outcome of active human cytomegalovirus infections in patients with prolonged treatment in an intensive care unit. Retrospective analysis of stored plasma samples. Anesthesiological intensive care unit of a university hospital. All 138 patients treated for at least 14 days (of a total of 4940 patients admitted during the study period). Immunocompromised patients and patients with inconclusive results for cytomegalovirus DNA were excluded. None. Stored plasma samples of patients with prolonged intensive care unit stay were tested for cytomegalovirus DNA. Sixty-four of 255 evaluable samples from 99 immunocompetent patients tested cytomegalovirus DNA-positive with a mean DNA concentration of 8,600 genome equivalents per milliliter. Active cytomegalovirus infection was diagnosed by reproducibly positive results in 35 patients (35%). Only one case had been diagnosed clinically. Patients with and without active cytomegalovirus infection were not significantly different in parameters, such as age, sex, admission category, source of admission, or comorbidities. Even review of specific surgical procedures or the use of a heart-lung-machine showed no significant differences between the groups. The mortality rate in patients with cytomegalovirus infection was significantly increased (28.6% vs. 10.9%, p = 0.048), and surviving patients had a longer intensive care unit stay (32.6 vs. 22.1 days, p <0.001). Active cytomegalovirus infection is a frequent but seldom diagnosed finding in surgical patients with prolonged intensive care unit stay, which is associated with increased mortality and prolonged intensive care unit stay of surviving patients.


Left Ventricular Systolic Dysfunction and Cardiovascular Outcomes in Tetralogy of Fallot: Systematic Review and Meta-analysis.
Although there are robust data about the pathophysiology and prognostic implications of left ventricular (LV) systolic dysfunction in patients with acquired heart disease, similar prognostic data about LV systolic dysfunction are sparse in the tetralogy of Fallot (TOF) population. The purpose of this study was to perform a meta-analysis of all studies that assessed the relationship between LV ejection fraction (LVEF) and cardiovascular adverse events (CAEs) defined as death, aborted sudden death, or sustained ventricular tachycardia. We used random-effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Of the 1,809 citations, 7 studies with 2,854 patients (age 28 ± 4 years) were included. During 5.6 ± 3.4 years' follow-up, there were 82 deaths, 17 aborted sudden cardiac deaths, and 56 sustained ventricular tachycardia events. Overall, CAEs occurred in 5.1% (144 patients). As a continuous variable, LVEF was a predictor of CAE (HR 1.29, 95% CI, 1.09-1.53, P = 0.001) per 5% decrease in LVEF. Similarly, LVEF < 40% was also a predictor of CAE (HR 3.22, 95% CI, 2.16-4.80, P < 0.001). LV systolic dysfunction was an independent predictor of CAE, and we observed a 30% increase in the risk of CAE for every 5% decrease in LVEF, and a 3-fold increase in the risk of CAE in patients with LVEF <40% compared with other patients. These findings underscore the importance of incorporating LV systolic function in clinical risk stratification of patients with TOF and the need to explore new treatment options to address this problem.


Nucleotide sequence and genetic organization of barley stripe mosaic virus RNA gamma.
The complete nucleotide sequences of RNA gamma from the Type and ND18 strains of barley stripe mosaic virus (BSMV) have been determined. The sequences are 3164 (Type) and 2791 (ND18) nucleotides in length. Both sequences contain a 5'-noncoding region (87 or 88 nucleotides) which is followed by a long open reading frame (ORF1). A 42-nucleotide intercistronic region separates ORF1 from a second, shorter open reading frame (ORF2) located near the 3'-end of the RNA. There is a high degree of homology between the Type and ND18 strains in the nucleotide sequence of ORF1. However, the Type strain contains a 366 nucleotide direct tandem repeat within ORF1 which is absent in the ND18 strain. Consequently, the predicted translation product of Type RNA gamma ORF1 (mol wt 87,312) is significantly larger than that of ND18 RNA gamma ORF1 (mol wt 74,011). The amino acid sequence of the ORF1 polypeptide contains homologies with putative RNA polymerases from other RNA viruses, suggesting that this protein may function in replication of the BSMV genome. The nucleotide sequence of RNA gamma ORF2 is nearly identical in the Type and ND18 strains. ORF2 codes for a polypeptide with a predicted molecular weight of 17,209 (Type) or 17,074 (ND18) which is known to be translated from a subgenomic (sg) RNA. The initiation point of this sgRNA has been mapped to a location 27 nucleotides upstream of the ORF2 initiation codon in the intercistronic region between ORF1 and ORF2. The sgRNA is not coterminal with the 3'-end of the genomic RNA, but instead contains heterogeneous poly(A) termini up to 150 nucleotides long (J. Stanley, R. Hanau, and A. O. Jackson, 1984, Virology 139, 375-383). In the genomic RNA gamma, ORF2 is followed by a short poly(A) tract and a 238-nucleotide tRNA-like structure.


Treatment of an ilio-caval thrombosis by mechanical thrombolysis.
In proximal deep vein thrombosis, thrombolytic treatment is more effective than heparin from a recanalization point of view but with a failure rate of 20%. We describe an interventional therapeutic procedure that may be effective in these cases. Mechanical thrombolysis with the thrombolizer (Angiocor, Lille Hellemmes, France) has been tried in 2 cases of deep vein thrombosis, when systemic thrombolysis alone had failed.


The observing subject and psychophysiological research: an epistemological discourse.
Realizing that scientific knowledge was not based on a simple disclosure of reality, but was rather invented and developed in accordance with our own conceptions and prejudices, it should no longer be possible to consider matters as if they existed independently of us 'out there'. Taking as examples the notions of 'memory' and 'information' we try to elucidate the relevance this perspective has with respect to neuro- and psychophysiological research.


Conditioned and unconditioned influences on body temperature and ethanol hypothermia in laboratory rats.
Both a naive group and a group of chronically handled rats were observed to develop hyperthermia when their cages (rats in situ) were removed from their usual positions on cage rack shelving and placed upon the laboratory bench for a period of 60 minutes. That procedure apparently functioned as a stressful unconditioned stimulus for the naive group. The extent of hyperthermia was more pronounced in the chronic group, presumably owing to the classical conditioning of environmental cues to the stressful events that had repeatedly been associated in the past with placement of the cage onto the benchtop. Doses of naloxone (10 mg/kg) and of ethanol (1 g/kg) that normally produced negligible effects on body temperature were found to significantly reduce the hyperthermia that developed when cages were placed onto the benchtop. The hypothermic response to 2 g/kg of ethanol was lessened in both groups by placement of the cages onto the benchtop.


Acquisition of additional primary chromosome abnormalities in the course of karyotype evolution in a case of FAB-M2 acute leukemia.
Cytogenetic studies of bone marrow metaphases from a 17-year-old woman with acute myeloid leukemia revealed a leukemic clone characterized by the t(8;21)(q22;q22) characteristic of FAB-M2. The patient was treated and achieved transient remissions. On relapse, her leukemic clone had acquired, in addition to the t(8;21), the inv(16)(p13q22) characteristic of FAB-M4Eo and a 5q- of the type seen in various acute myeloid leukemias and myelodysplastic syndromes. This cell line persisted throughout the remainder of the patient's clinical course. There were no other clonal chromosome abnormalities observed. The observation of multiple chromosome mutations, usually regarded separately as primary, in a single leukemic clone is most unusual and raises questions about our concepts of the nature of primary acquired chromosome mutations in cancer.


[Risk of osteoporotic fracture and hip fracture in patients with chronic obstructive pulmonary disease].
Osteoporosis is a frequent comorbidity in patients with chronic obstructive pulmonary disease (COPD). We have studied the risk of major osteoporotic fracture and hip fracture in patients with COPD. A multicenter cross-sectional study was performed in Spain in 26 hospitals of 16 regional communities. Patients diagnosed with COPD who required admission to the Internal Medicine Service due to exacerbation of their respiratory disease were enrolled. COPD was confirmed by post-bronchodilator spirometry in stable state: maximum expiratory volume in the first second (FEV₁) < 80% of the theoretical value and quotient FEV(1)/FVC < 0.70 and percent predicted after the administration of a bronchodilator. Dyspnea was evaluated with the modified Medical Research Council (mMRC) dyspnea scale. The principal variable was the likelihood of fracture evaluated with the FRAX® tool for the Spanish population. Three hundred and ninety two patients, 347 (88%) men, with a mean (SD) age of 73.7 (8.9) years and a mean FEV₁ of 1.23 liters (43.3% of predicted) were enrolled. Only 37 patients (9.4%), 27 men and 10 women had been diagnosed previously of osteoporosis. Overall, 1.8% (95% CI: 0.9-3.6) had a 10-year probability of major osteoporotic fracture ≥ 20% and 49.7% (95% CI: 44.8-54.7) had a probability of hip fracture ≥ 3%. No relationship was observed between the probability of fracture and GOLD stage or mMRC dyspnea scale. The diagnosis of osteoporosis is uncommon in our COPD patients. However, half of them have a high probability of a hip fracture in the next 10 years.


Highly reusable invertase biocatalyst: Biological fibrils functionalized by photocrosslinking.
Here we report a novel strategy for the immobilization of invertase using amyloid-like fibrils as a support. Optimal conditions to get Tyr-Tyr covalent binding between invertase and the support were determined using a photocrosslinking approach. The biological fibrils with invertase activity turn into microstructured catalysts according to electron microscopy outcomes. Thermal and storage stability as well as optimal pH and temperature of the enzyme were conserved. Moreover, the immobilized enzyme recovered by low g-force centrifugation retained 83% of its initial enzymatic activity after 15 reuse cycles. Considering that enzyme cost is the most significant part of the overall fee of enzymatic biomass conversion, the highly efficient recovery/reuse strategy described herein becomes relevant. Besides, it can also be applied to the immobilization of other enzymes for industrial biocatalysis.


Jian-Pi-Yin decoction attenuates lactose-induced chronic diarrhea in rats by regulating GLP-1 and reducing NHE3 ubiquitination and phosphorylation.
Jian-Pi-Yin decoction (JPY), a prescription derived from the traditional Chinese medicine Shen-Ling-Bai-Zhu-San, has shown good clinical efficacy in the treatment of diarrhea caused by lactose intolerance. However, the mechanism of action of JPY in the treatment of diarrhea is not fully understood. In this study, a rat diarrhea model was induced by high lactose feeding combined with standing on a small platform to investigate the ameliorating effect of JPY on hyper lactose-induced diarrhea in rats and its possible mechanism. The rat model of hyper lactose diarrhea was given high, medium, and low doses of JPY and the positive control drug Smida by gavage for 1 week. At the same time, NA+-H+ exchanger 3 (NHE3) inhibitor Tenapanor was administered orally for 3 weeks. Body weight, food intake, water intake, grip strength, and severity of diarrhea symptoms were measured in rats throughout the study. The serum, colon, and jejunum tissues of the model and drug-treated rats were collected for histopathological examination and analysis of relevant indicators. JPY significantly alleviated the symptoms of fatigue, diet reduction and diarrhea in the model group. Glucagon-like peptide-1 (GLP-1) and cyclic adenosine monophosphate (cAMP) expression were also down-regulated after JPY treatment. JPY can significantly promote NHE3 in intestinal tissues of rats with diarrhea, and the mechanism is related to the decrease of GLP-1, inhibition of cAMP/PKA pathway activation, an increase of ubiquitin-specific protease 7 (USP7) and USP10 expression, and decrease of NHE3 ubiquitination and phosphorylation. JPY can reduce the expression of GLP-1, reduce the ubiquitination and phosphorylation of NHE3, regulate the expression of NHE3, at least partly improve ion transport in the intestinal epithelium, and improve the imbalance of electrolyte absorption, thus significantly reducing the diarrhea symptoms of rats with high lactose combined with small platform standing. In this study, we explored the mechanism of intestinal GLP-1 activation of cAMP/PKA signaling pathway from multiple dimensions, and increased its expression by reducing phosphorylation and ubiquitination of NHE3, thereby treating chronic diarrhea associated with lactose intolerance.


Lupus nephritis associated with positive MPO-ANCA in a patient with underlying autoimmune hemolytic anemia.
A 19-year-old female was admitted with general malaise and systemic edema. She had been diagnosed as having autoimmune hemolytic anemia (AIHA) eight years earlier and was successfully managed with oral prednisolone. During the current admission, she was diagnosed as having systemic lupus erythematosus (SLE) based on the presence of renal involvement, hematological abnormalities, and antinuclear and anti-double-stranded DNA antibodies, along with a recurrence of AIHA; her serology revealed a high myeloperoxydase-antineutrophil cytoplasmic antibody (MPO-ANCA) titer. She was treated with prednisolone (50 mg day(-1)), but her renal function started to deteriorate. She responded to treatment with hemodialysis, plasmapheresis, and methylprednisolone pulse therapy; her MPO-ANCA titer and renal function improved. Treatment with intravenous cyclophosphamide gradually suppressed her AIHA and SLE activity. A renal biopsy revealed a diffuse proliferative lupus nephritis (class IV-G (A)) with necrotizing crescentic glomerulonephritis that was presumed to be associated with MPO-ANCA. The association of MPO-ANCA with SLE in this refractory case is discussed.


Ocular pneumoplethysmography in cardiac pacing.
Variations in ocular blood flow (OBF) reflect variations in cardiac stroke output very closely. The use of ocular pneumoplethysmography (OPG-Gee) for the measurement of OBF is a simple, noninvasive method of assessing the hemodynamics of ventricular versus atrioventricular sequential pacing.


Long-Term (≥25 Years) Kidney Allograft Survivors: Retrospective Analysis at a Single Center.
Despite great improvements in the short-term patient and kidney graft survival, the long-term morbidity and mortality in kidney transplant recipients still remains a significant problem. The aim of the study was to evaluate the impact of both donor and transplant recipient factors, as well as renal function indices on the very long-term (>25 years) kidney allograft survival. Retrospective analysis was performed on the data of 41 kidney transplant recipients (KTR), group A: follow-up = 25 years, 20 KTR, 10 male, mean age (mean [M] ± standard deviation [SD]): 34.6 ± 12.6 years, 14 living donors (LD), 6 cadaveric donors (CD); group B: follow-up > 25 years, 21 KTR, 16 male, mean age (M ± SD): 30.86 ± 12.37 years, 14 LD, 7 CD). Kidney graft origin, post-kidney transplantation diabetes mellitus, HLA compatibility, delayed graft function, and acute rejection episodes were also analyzed retrospectively. Statistical analysis with Mann-Whitney test and Kaplan-Meier survival analysis was performed (SPSS 20.0 for Windows). The mean age of CDs was lower than that of LDs: CD mean age (M ± SD): 23.84 ± 16.26 years vs LD mean age: 52.75 ± 12.42 years (P < .001). Cadaveric kidney graft was associated with better renal allograft function 10, 15, and 25 years post kidney transplant. None of the other factors analyzed reached statistical significance between the 2 groups. The age of the donor and the kidney graft origin are important co-factors of the very long-term kidney allograft survival.


Olfactory recognition memory is disrupted in young mice with chronic low-level lead exposure.
Chronic developmental lead exposure yielding very low blood lead burden is an unresolved child public health problem. Few studies have attempted to model neurobehavioral changes in young animals following very low level exposure, and studies are needed to identify tests that are sensitive to the neurobehavioral changes that may occur. Mechanisms of action are not yet known however results have suggested that hippocampus/dentate gyrus may be uniquely vulnerable to early chronic low-level lead exposure. This study examined the sensitivity of a novel odor recognition task to differences in pre-adolescent C57BL/6J mice chronically exposed from birth to PND 28, to 0 ppm (control), 30 ppm (low-dose), or 330 ppm (higher-dose) lead acetate (N=33). Blood lead levels (BLLs) determined by ICP-MS ranged from 0.02 to 20.31 μg/dL. Generalized linear mixed model analyses with litter as a random effect showed a significant interaction of BLL×sex. As BLLs increased olfactory recognition memory decreased in males. Among females, non-linear effects were observed at lower but not higher levels of lead exposure. The novel odor detection task is sensitive to effects associated with early chronic low-level lead exposure in young C57BL/6J mice.


Effects of dextran sulphate (DXS) on lymphocyte localization in complement-deficient mice: evidence that the fifth component of complement is not implicated in the DXS activity.
The effects of subcutaneously or intraperitoneally administered dextran sulphate (DXS) (50 mg/Kg) on the subsequent 1 h localization of intravenously injected radiolabelled lymph node cells was investigated in complement deficient mice which lack C5. DXS proved to be equally as potent in depressing cell localization in deficient as compared to normal mice. These findings indicate that the terminal complement components are not essential for DXS activity.


New insights into the immune regulation and tissue repair of Litopenaeus vannamei during temperature fluctuation using TMT-based proteomics.
To investigate shrimp immunoregulation and tissue self-repair mechanism during temperature fluctuation stage, Litopenaeus vannamei (L. vannamei) was treated under conditions of gradual cooling from an acclimation temperature (28 °C, C group) to 13 °C (T group) in 2 days with a cooling rate of 7.5 °C/d and then rewarmed to 28 °C (R group) with the same rate. Tandem mass tags (TMT) -based proteomics technology was used to investigate the protein abundance changes of intestine in L. vannamei during temperature fluctuation. The results showed that a total of 5796 proteins with function annotation were identified. Of which, the abundances of 1978 proteins (34%) decreased after cooling and then increased after rewarming, 1498 proteins (26%) increased during the whole stage, 1263 proteins (22%) increased after cooling and then decreased after rewarming and 1057 proteins (18%) decreased during the whole stage. Differentially expressed proteins such as C-lectin, NFκBIA and Caspase may contributed to the regulation of immunity and tissue repair of shrimp intestine during the temperature fluctuation stage. These findings contribute to the better understanding of shrimp' regulatory mechanism against adverse environment.


CLEVER assay: A visual and rapid RNA extraction-free detection of SARS-CoV-2 based on CRISPR-Cas integrated RT-LAMP technology.
The current scenario of COVID-19 pandemic has presented an almost insurmountable challenge even for the most sophisticated hospitals equipped with modern biomedical technology. There is an urgency to develop simple, fast and highly accurate methods for the rapid identification and isolation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients. To address the ongoing challenge, the present study offers a CLEVER assay (CRISPR-Cas integrated RT-LAMP Easy, Visual and Extraction-free RNA) which will allow RNA extraction-free method to visually diagnose COVID-19. RNA extraction is a major hurdle in preventing rapid and large-scale screening of samples particularly in low-resource regions because of the logistics and costs involved. Herein, the visual SARS-CoV-2 detection method consists of RNA extraction-free method directly utilizing the patient's nasopharyngeal and oropharyngeal samples for reverse transcription loop-mediated isothermal amplification (RT-LAMP). Additionally, the assay also utilizes the integration of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas12-based system using different guide RNAs of N, E and an internal control POP7 (human RNase P) genes along with visual detection via lateral flow readout-based dip sticks with unaided eye (~100 min). Overall, the clinical sensitivity and specificity of the CLEVER assay were 89.6% and 100%, respectively. Together, our CLEVER assay offers a point-of-care tool with no equipment dependency and minimum technical expertise requirement for COVID-19 diagnosis. To address the challenges associated with COVID-19 diagnosis, we need a faster, direct and more versatile detection method for an efficient epidemiological management of the COVID-19 outbreak. The present study involves developing a method for detection of SARS-CoV-2 in human body without RNA isolation step that can visually be detected with unaided eye. Taken together, our assay offers to overcome one major defect of the prior art, that is, RNA extraction step, which could limit the deployment of the previous assays in a testing site having limited lab infrastructure.


Early changes of cyclic nucleotide levels in a mitogenic reaction in the rat mesentery.
By measuring simultaneously cAMP and cGMP we found a biphasic time course with regard to cGMP and the cGMP/cAMP ratio very early in a mitogenic reaction in vivo. This is a new finding.


Production of heterologous glycoproteins by a glycosylation-defective alg3och1 mutant of Schizosaccharomyces pombe.
The early stages of N-linked glycosylation are highly conserved between fungal and mammalian cells. Such N-linked oligosaccharides are synthesized through the ordered assembly of a dolichyl pyrophosphate (Dol-PP)-linked Glc(3)Man(9)GlcNAc(2) structure by the sequential actions of several glycosyltransferases located in the endoplasmic reticulum (ER). Of the glycosyltransferase genes, Saccharomyces cerevisiae ALG3 has been identified to encode the Dol-P-Man:Man(5)GlcNAc(2)-PP-Dol α1,3-mannosyltransferase, and an alg3 mutant has been shown to accumulate an Endo H-resistant M5B (Manα1,2-Manα1,2-Manα1,3(Manα1,6-)-Manβ1,4-GlcNAcβ1,4-GlcNAc) structure. Although Schizosaccharomyces pombe contains a homolog of the ALG3 gene (SPAC7D4.06c), the role of this gene in oligosaccharide biosynthesis is not at all clear. In this study, we deleted the alg3(+) gene in the och1Δ mutant and analyzed the detailed oligosaccharide structures in alg3Δoch1Δ double mutant. The oligosaccharides were prepared from cell-surface glycoproteins by hydrazinolysis and fluorescent labeling with 2-aminopyridine. The labeled oligosaccharides were analyzed by high performance liquid chromatography, in combination with sequential glycosidase digestion and methylation analysis. These analyses revealed that the N-linked oligosaccharides of S. pombe alg3Δoch1Δ cells mainly consisted of two or three α-galactose-capped M5B structures. Finally, western blot analysis of recombinant human transferrin suggested that heterologously expressed glycoproteins in alg3Δoch1Δ cells have Endo H-resistant N-linked oligosaccharide structures similar to those of alg3Δoch1Δ cell-surface glycoproteins.


[Biologic behavior and prognosis of patients with gastric cancer in young persons].
To explore the relationship between the biological behavior and prognostic factors in treating gastric cancer of young persons by various surgical methods. 89 young patients with gastric cancer aged 35 years or less were analyzed. The resectable rate was 73.0% (65/89), radical resectable rate 48.3% (43/89), and palliative resectable rate 24.7% (22/89). The 5-year survival rate was 24.7% (22/89) and 48.8% (21/43) for the radical group. Biological characteristics included infiltrated, diffused growth, lymph node metastasis, female predominance. The biological behavior of gastric cancer in young persons is poor. Early management gastric cancer and radical operation combined with complex treatment are essential.


The reliability and validity of provocative food testing: a critical review.
Clinical reports have advocated intradermal and sublingual provocative food testing as effective methods of identifying food sensitivities. However, studies assessing their reliability and/or validity have generally reached negative conclusions. These studies commonly have serious flaws in design and analysis. These include: (1) the administration of food antigens to subjects without verifying sensitivity to them, and then comparing responses to antigens and placebos, (2) the failure to implement double-blind procedures with placebo controls, (3) the failure to analyse results statistically, and (4) improper statistical analysis. In some cases, re-analysis of the data provided seriously affects the conclusions of the study. Overall, the evidence suggests that both intradermal and sublingual provocative food tests are capable of provoking reactions above placebo levels, but whether they are sufficiently reliable and valid to be clinically useful is questionable.


Determination of dissociation constants and relative efficacies of some potent muscarinic agonists at postjunctional muscarinic receptors.
This study was undertaken to determine dissociation constants (KA and relative efficacies (er) of seven muscarinic agonists (methylfurtrethonium; dioxolane, oxathiolane, carbachol, muscarine, muscarone and oxotremorine) in three isolated tissues (guinea-pig ileum and atria and rat urinary bladder). The rank order of affinities (-log KA) of the various compounds varied depending on the tissue used. er values for the different agonists did not differ significantly from each other in any of the three tissues, except that the er of muscarine in the guinea-pig ileum was higher than those of the other compounds and that of oxotremorine in the rat urinary bladder was lower than those of the other agonists. Comparisons among tissues show that KA and er values were the same in different tissues for some compounds (muscarone, muscarine and methylfurtrethonium), while significant differences were found for the other compounds. This suggests the existence of a discrete receptor population recognized by some but not all agonists. For oxotremorine er as well as -log KA, is greater in atria than in smooth muscle: these factors combine to determine the cardioselectivity of this compound which can now ascribed to receptor selectivity.


The amino acid composition of the zinc-induced metallothionein isoforms in rat brain.
Recent investigation from this laboratory has identified in the rat brain a zinc-inducible and actinomycin D-inhibited metallothionein with an elution volume (Ve/Vo) of 2.08 and a molecular weight of smaller than 10,000 daltons. Furthermore, purification of the zinc-induced metallothionein by ion exchange chromatography on DEAE-Sephadex A-25 columns produced two isoforms, eluting, respectively, at 68 and 130 mM of Tris-acetate buffer, pH 7.5. In this paper, we report that zinc-induced metallothionein produces also two distinct isoforms on reverse phase high performance liquid chromatography that exhibit retention times of 17.23 and 18.53 minutes, respectively. Brain metallothionein was characterized further by studies showing that the zinc-induced metallothionein incorporated a large quantity of [35S]cysteine and that isoforms I and II contain 17 and 18 cysteine residues, respectively, while being devoid of any arginine, histidine, leucine, phenylalanine or tyrosine. The precise functions of the brain metallothionein isoforms, which may be related to the transport and homeostasis of essential elements such as zinc and copper, remain to be elucidated.


Analyzing trichomes and spatio-temporal expression of a cysteine protease gene Mucunain in Mucuna pruriens L. (DC).
Mucuna pruriens is a well-known legume for the itching attributes of the trichome and a valuable medicinal herb that is used for the treatment of Parkinson's disease, sexual debilities, etc. Its cultivation was deprived due to its itching behavior. The wild genotype of M. pruriens have the largest trichome length (2015 ± 29 μm) compared to other genotype and mutants. The white-seeded variety of M. pruriens was found to be the most suitable for large-scale cultivation due to the small trichome size and less trichome density on the pod. The external surface trichomes have protuberance with unknown function. The unicellular trichomes of Mucuna show the flowing fluid or cytoplasm inside the trichome. The unigenes regulating the differentiation and development of the trichome such as GLABRA-1, GLABRA-2, and cpr-5 have been identified in M. pruriens transcriptome of the leaf. The Mucunain shows a higher transcript abundance in the flower and pod cover compared to the seeds. The Mucunain was found in every stage of plant growth, but it was highly expressed during maturity (about 170 days) with a high fragment per kilobase per million value.


A Mg2+/polydopamine composite hydrogel for the acceleration of infected wound healing.
Bacterial infection is a vital factor to delay the wound healing process. The antibiotics abuse leads to drug resistance of some pathogenic bacteria. Non-antibiotic-dependent multifunctional biomaterials with accelerated wound healing performance are urgently desired. Herein, we reported a composite antibacterial hydrogel PDA-PAM/Mg2+ that shows excellent self-healing and tissue adhesive property, and photothermal antibacterial functions for accelerating wound healing. The gel was composed of polyacrylamide (PAM), polydopamine (PDA), and magnesium (Mg2+) and prepared via a two-step procedure: an alkali-induced dopamine pre-polymerization and followed radical polymerization process. The composite gel shows excellent tissue adhesiveness and Mg2+-synergized photothermal antibacterial activity, inducing a survival rate of 5.29% for S. aureus and 7.06% for E. coli after near infrared light irradiation. The composite hydrogel further demonstrated efficient bacteria inhibition, enhanced wound healing and collagen deposition in a full-thickness skin defect rat model. Together, the PDA-PAM/Mg2+ hydrogel presents an excellent wound dressing with excellent tissue adhesion, wound healing, and antibacterial functions.


Occupational medical prophylaxis for the musculoskeletal system: A function-oriented system for physical examination of the locomotor system in occupational medicine (fokus(C)).
Occupational physicians are very often confronted with questions as to the fitness of the postural and locomotor systems, especially the spinal column. Occupational medical assessment and advice can be required by patients with acute symptoms, at routine check-ups, by persons who have problems doing certain jobs, and for expert medical reports as to the fitness of persons with chronic disorders or after operations. Therefore, for occupational medical purposes a physical examination must aim primarily to investigate functions and not structures or radiologic evidence. The physical examination should be structured systematically and according to regions of the body and, together with a specific (pain) anamnesis should provide a basis for the medical assessment.This paper presents a function-oriented system for physical examination of the locomotor system, named fokus(C) (Funktionsorientierte Koerperliche Untersuchungssystematik, also available on DVD). fokus(C) has been developed with a view to its relevance for occupational medical practice and does not aim primarily to provide a precise diagnosis. Decisive for an occupational medical assessment of disorders of the musculoskeletal system is rather information about functional disorders and any impairment of performance or mobility which they can cause. The division of the physical examination into a rapid screening phase and a subsequent more intensive functional diagnostic phase has proved its practicability in many years of day-to-day use. Here, in contrast to the very extensive measures recommended for orthopaedic and manual diagnosis, for reasons of efficiency and usability of the system in routine occupational medical examinations the examination is structured according to the findings. So it is reduced to that which is most necessary and feasible.


E2A proteins enhance the histone acetyltransferase activity of the transcriptional co-activators CBP and p300.
The E2A gene encodes the E-protein transcription factors E12 and E47 that play critical roles in B-lymphopoiesis. A somatic chromosomal translocation detectable in 5% of cases of acute lymphoblastic leukemia (ALL) involves E2A and results in expression of the oncogenic transcription factor E2A-PBX1. CREB binding protein (CBP) and its close paralog p300 are transcriptional co-activators with intrinsic histone acetyltransferase (HAT) activity. We and others have shown that direct binding of an N-terminal transcriptional activation domain present in E12/E47 and E2A-PBX1 to the KIX domain of CBP/p300 contributes to E2A protein function. In the current work we show for the first time that the catalytic HAT activity of CBP/p300 is increased in the presence of residues 1-483 of E2A (i.e., the portion present in E2A-PBX1). The addition of purified, recombinant E2A protein to in vitro assays results in a two-fold augmentation of CBP/p300 HAT activity, whereas in vivo assays show a ten-fold augmentation of HAT-dependent transcriptional induction and a five-fold augmentation of acetylation of reporter plasmid-associated histone by CBP in response to co-transfected E2A. Our results indicate that the HAT-enhancing effect is independent of the well-documented E2A-CBP interaction involving the KIX domain and suggest a role for direct, perhaps low affinity binding of E2A to a portion of CBP that includes the HAT domain and flanking elements. Our findings add to a growing body of literature indicating that interactions between CBP/p300 and transcription factors can function in a specific manner to modulate HAT catalytic activity.


Cardiovascular challenges in toxicology.
The diagnoses and subsequent treatment of poisoned patients manifesting cardiovascular compromise challenges the most experienced emergency physician. Numerous drugs and chemicals cause cardiac and vascular disorders. Despite widely varying indications for therapeutic use, many agents share a common cardiovascular pharmacologic effect if taken in overdose. Standard advanced cardiac life support protocol care of these patients may not apply and may even result in harm if followed. This chapter discusses com-mon cardiovascular toxins and groups them into their common mechanisms of toxicity. Multiple agents exist that result in human cardiovascular toxicity. The management of the toxicity of each agent should follow a rationale approach. The first step in the care of all poisoned patients focuses on good supportive care.


Outcomes after ileoanal pouch surgery in frail and older adults.
Evidence from single-center studies suggests that ileal pouch-anal anastomosis (IPAA) can be safely performed in selected older patients with ulcerative colitis. The impact of age and frailty on surgical outcomes and hospital length of stay after IPAA has not been examined. We identified all patients with ulcerative colitis who underwent total proctocolectomy or completion proctectomy with IPAA in the National Surgery Quality Improvement Program database from 2005-2012. We examined the associations of age and frailty trait count with length of hospital stay and surgical complications using multivariate regression. IPAA was performed in 2493 patients with ulcerative colitis. Thirty-day mortality was 0.2% (n = 6). The majority of patients had no serious postoperative complications (age ≤50 y: 79.5%, age 51-60 y: 80.4%, and age >60 y: 79.1%). After multivariate risk adjustment, patients aged >60 y had a similar mean number of complications as patients aged ≤50 y (0.31 versus 0.35, P = 0.47) and a 0.8-d longer mean length of hospital stay (7.4 versus 8.2 d, P = 0.035). Compared to patients with zero frailty traits, a frailty trait count ≥1 was associated with a similar mean number of complications (0.31 versus 0.34, P = 0.36) and length of hospital stay (7.4 versus 7.7 d, P = 0.25). In this analysis of patients undergoing IPAA at National Surgery Quality Improvement Program hospitals, surgical complications were not substantially increased in older patients or those with frailty traits. Older age was associated with a small increase in hospital length of stay. These findings suggest that IPAA is safe in selected older adults with ulcerative colitis.


Protooncogene structure in the cancer family syndrome.
Protooncogene loci in constitutional DNA from affected members of a kindred with the cancer family syndrome were studied by Southern blot hybridization analysis. No structural rearrangements or amplification of 16 protooncogenes were detected. These studies demonstrated that gross structural alteration of the tested protoocongenes is not responsible for cancer susceptibility in this syndrome.


Expression of S100 protein family members in normal skin and sweat gland tumors.
Despite our growing knowledge regarding the biology of S100 family proteins in cancers and internal diseases, limited data are available with their distribution in normal skin and in sweat gland tumors. To study the expression and distribution pattern of multiple S100 proteins in normal skin and in the tumors of sweat glands. Immunohistological staining was performed using S100A2, S100A4, S100A6, S100A7, S100A8/9, S100A11, and S100P in 41 cases of various kinds of sweat gland tumors and in 13 cases of normal skin. In normal skin, S100A2, S100A6, S100A7, and S100P staining were observed in the sweat glands. S100A2 positively stained in the outer layer of the eccrine duct. S100A6 immunolabeling was observed in the secretory portion of the eccrine gland. Myoepithelial cells of the apocrine gland were positive for S100A2 and S100A6. S100A7 was positive in the acrosyringium, ductal, and secretory portions of the eccrine gland and in the inner layer of the apocrine gland. Intense S100P staining was detected in the inner layer of the acrosyringium and eccrine ducts. Langerhans cells and melanocytes showed strong immunoreactivity to S100A4. Extramammary Paget's disease (EMPD) expressed S100A7 and S100P with partial S100A6 and S1004 staining. Eccrine poroma expressed S100A2 and S100A7 with partial labeling with S100A6. Syringoma expressed S100A2, S1007, and S100P. Apocrine hidrocystoma expressed S100A2 with partial S100A6 and S100A7 immunoreactivity. Syringocystadenoma papilliferum expressed S100A2, S100A6, S100A7, and S100P. S100A2, S100A6, S100A7, and S100P proteins are specifically involved in structure-related distribution and are potentially useful for differential diagnoses of sweat gland tumors.


Primary extensive pyomyositis in an immunocompetent patient: case report and literature review.
Pyomyositis is a suppurative infection of the skeletal muscle; it mainly occurs in immunocompromised patients or, exceptionally, in immunocompetent patients in tropical or other areas. We present a 24-year-old immunocompetent lady with bilateral thigh myalgia and fever. Upon investigation, extensive multifocal bilateral fluid collections involving the extensor muscles of both thighs were demonstrated. Pus aspirate from the involved muscles proved the presence of Staphylococcus aureus. Incision and drainage of the involved muscles were performed with successful and complete recovery.