Situational social influence leading to non-compliance with conservation rules.
It is well established that the decisions that we make can be strongly influenced by the behaviour of others. However, testing how social influence can lead to non-compliance with conservation rules during an individual's decision-making process has received little research attention. We synthesise advances in understanding of conformity and rule-breaking in individuals and in groups, and take a situational approach to studying the social dynamics and ensuing social identity changes that can lead to non-compliant decision-making. We focus on situational social influence contagion that are copresent (i.e., same space and same time) or trace-based (i.e., behavioural traces in the same space). We then suggest approaches for testing how situational social influence can lead to certain behaviours in non-compliance with conservation rules.


Incidence and risk factors of isolated calf muscular venous thrombosis after tibial plateau fractures surgery.
The risks associated with deep vein thrombosis (DVT) have gained significant recognition over time. A prevalent form of distal DVT is isolated calf muscular venous thrombosis (ICMVT). Despite its common clinical occurrence, data on ICMVT subsequent to tibial plateau fracture (TPF) surgery are scarce. This study aimed to examine the epidemiological characteristics and associated risk factors (RFs) of ICMVT following TPF surgery. For this retrospective analysis, we included patients from our hospital, who underwent TPF surgery between March 2017 and March 2021. Patients' electronic medical records were reviewed, including admission details, fracture classification, surgical procedures, and laboratory biomarkers. The HSS (The American Hospital for Special Surgery) and Rasmussen scores were employed to evaluate the clinical effect. A Color Duplex Flow Imager (CDFI) was regularly used to detect pre- and postoperative venous thrombosis in the lower limbs. Finally, uni- and multivariate logistic regression analyses were used to identify independent RFs associated with ICMVT. Overall, 481 participants were recruited for analysis. Postoperative ICMVT occurred in 47 patients. All ICMVTs occurred on the affected side. Four of the 47 ICMVT patients exhibited sudden postoperative swelling in the affected limb. The HSS and Rasmussen scores in the non-ICMVT cohort (87.6 ± 8.2, 16.0 ± 1.7) were markedly different from the ICMVT cohort (84.8 ± 8.2, 15.5 ± 1.6) (p = 0.014, p = 0.031). This study finally identified five postoperative ICMVT-related RFs, which were age (> 55 years old) (OR 3.06; 95% CI 1.47-6.37; p = 0.003), gender (female) (OR 2.67; 95% CI 1.37-5.22; p = 0.004), surgical duration (> 114 min) (OR 3.14; 95% CI 1.44-6.85; p = 0.004), elevated white blood cell content (OR 2.85; 95% CI 1.47-5.51; p = 0.002), and hyponatremia (OR 2.31; 95% CI 1.04-5.12; p = 0.040). The epidemiological findings of this study may help predict ICMVT risk after surgery thus facilitating the development of individualized clinical assessments and targeted prevention programs.


Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer.
Irinotecan (CPT-11) is a chemotherapeutic drug for cancer that causes severe diarrhea by an uncertain mechanism. The aim of the present study was to investigate the time-course of apoptosis and whole intestinal damage after irinotecan to further elucidate the mechanism behind the diarrhea. Groups of breast cancer-bearing dark agouti (DA) rats were treated with 100, 150 or 200 mg/kg doses of irinotecan or vehicle control daily for two days, and killed at 6, 24, 72 or 96 h after treatment. Apoptosis and morphometry were examined in both the small and large intestines. Histopathology and goblet cell numbers were recorded. Data were analyzed using the Peritz' F-test. Irinotecan increased apoptosis and caused villous atrophy and crypt hypoplasia in the small intestine, and increased apoptosis, crypt hypoplasia, crypt dilation and mucus secretion in the large intestine. Irinotecan at 100 and 150 mg/kg caused crypt hypoplasia at 6 and 24 h, with rebound hyperplasia at 72 and 96 h. At 200 mg/kg, irinotecan caused a more pronounced crypt hypoplasia earlier and all animals died by 96 h. Apoptosis peaked at 6 h and remained elevated over the remainder of the time-points. This was not dose-dependent. Irinotecan at all doses altered colonic, but not jejunal, goblet cells. Irinotecan increased colonic mucus secretion. We conclude that irinotecan causes diarrhea by inducing apoptosis and hypoproliferation in both the small and large intestines, and causes colonic damage with changes in goblet cells and mucin secretion.


The human alpha 2(IV) collagen gene, COL4A2, is syntenic with the alpha 1(IV) gene, COL4A1, on chromosome 13.
We have previously assigned the gene for the alpha 1 chain of type IV collagen to chromosome 13. In this report we show that the gene coding for the second chain of this heterotrimer is on the same chromosome. This is the first example of the genes for both chains of one collagen molecule being syntenic.


Patient-specific iPSC-derived cardiomyocytes reveal variable phenotypic severity of Brugada syndrome.
Brugada syndrome (BrS) is a cardiac channelopathy that can result in sudden cardiac death (SCD). SCN5A is the most frequent gene linked to BrS, but the genotype-phenotype correlations are not completely matched. Clinical phenotypes of a particular SCN5A variant may range from asymptomatic to SCD. Here, we used comparison of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) derived from a SCN5A mutation-positive (D356Y) BrS family with severely affected proband, asymptomatic mutation carriers (AMCs) and healthy controls to investigate this variation. 26 iPSC lines were generated from skin fibroblasts using nonintegrated Sendai virus. The generated iPSCs were differentiated into cardiomyocytes using a monolayer-based differentiation protocol. D356Y iPSC-CMs exhibited increased beat interval variability, slower depolarization, cardiac arrhythmias, defects of Na+ channel function and irregular Ca2+ signaling, when compared to controls. Importantly, the phenotype severity observed in AMC iPSC-CMs was milder than that of proband iPSC-CMs, an observation exacerbated by flecainide. Interestingly, the iPSC-CMs of the proband exhibited markedly decreased Ca2+ currents in comparison with control and AMC iPSC-CMs. CRISPR/Cas9-mediated genome editing to correct D356Y in proband iPSC-CMs effectively rescued the arrhythmic phenotype and restored Na+ and Ca2+ currents. Moreover, drug screening using established BrS iPSC-CM models demonstrated that quinidine and sotalol possessed antiarrhythmic effects in an individual-dependent manner. Clinically, venous and oral administration of calcium partially reduced the malignant arrhythmic events of the proband in mid-term follow-up. Patient-specific and genome-edited iPSC-CMs can recapitulate the varying phenotypic severity of BrS. Our findings suggest that preservation of the Ca2+ currents might be a compensatory mechanism to resist arrhythmogenesis in BrS AMCs. National Key R&D Program of China (2017YFA0103700), National Natural Science Foundation of China (81922006, 81870175), Natural Science Foundation of Zhejiang Province (LD21H020001, LR15H020001), National Natural Science Foundation of China (81970269), Key Research and Development Program of Zhejiang Province (2019C03022) and Natural Science Foundation of Zhejiang Province (LY16H020002).


The use of sensory evoked potentials in toxicology.
The rationale for studying sensory systems as an integral part of neurotoxicological examinations is presented. The role of evoked potentials in assessing brain dysfunction in general and sensory systems in particular is also presented. Four types of sensory evoked potentials (brainstem auditory evoked response, somatosensory evoked potentials, flash evoked potentials, and pattern reversal evoked potentials) are discussed in terms of their demonstrated contributions to neurotoxicology and clinical neurology. Research needed to allow these methods to achieve their full value for neurotoxicology is identified and briefly discussed.


Comparison of the binding characteristics of two different preparations of tetanus toxin to rat brain membranes.
Two different preparations of tetanus toxin (HTT and WTT) were iodinated, and their binding to rat brain membranes characterized. Under optimal binding conditions (25 mM Tris-acetate, pH 6.0), both preparations bound to a large number of high affinity sites, thought to be gangliosides. Binding constants were identical. However, in a physiological buffer (Krebs-Ringer, pH 7.4) binding of the two toxin preparations showed a number of differences. Under these conditions we have previously shown that HTT binding is markedly reduced, and that there are two classes of sites, a small number of heat-, sialidase- and protease-sensitive high affinity sites, and a larger number of sialidase-sensitive, heat- and protease-resistant lower affinity sites, probably gangliosides (PIERCE et al. (1986) Biochem. J. 236, 845-852). Although WTT bound to these same two sites, it displayed a higher affinity for the protease-resistant site than did HTT. WTT also bound to free or immobilized trisialoganglioside with higher affinity than HTT, consistent with the view that the protease-resistant site represents binding to ganglioside. In contrast, both toxin preparations bound to the protease-sensitive site with similar affinities. These observations may explain the four to five-fold higher levels of WTT binding to brain membranes, and the fact that a smaller percentage of total WTT binding is protease sensitive. Despite their different ganglioside-binding properties, both toxin preparations showed comparable neurotoxic activities, and appeared identical on SDS gels.


Prognostic value of total lesion glycolysis and metabolic active tumor volume in non-small cell lung cancer.
To predict the outcome of patients with non-small cell lung cancer (NSCLC) the currently used prognostic system (TNM) is not accurate enough. The prognostic significance of the SUVmax measured by PET remains controversial. This study aims to evaluate the prognostic value in overall survival and progression free survival of SUVmax, the total lesion glycolysis (TLG) and the mean metabolic active volume (MATV) in NSCLC. We retrospectively reviewed 105 patients (72 males, 33 females) with a new diagnosis of NSCLC (TNM stage I: 27.6%, II: 10.5%, III: 40.9% and IV: 21.0%) who underwent scanning with a PET/CT. For VOI definition a semi-automatic delineation tool was used. On PET images SUVmax, SUVmean and MATV of the primary tumor and the whole tumor burden were measured. TLG and MATV were measured by using a threshold of 50% of SUVmax. OS and PFS are found to be higher in patients with low-SUVTmax and low-TLGT values. OS and PFS were significantly higher for low-SUVWTBmax, low-MATVWTB and low-TLGWTB values of the whole-tumor burden. Multivariate analysis of the whole-tumor burden revealed that the most important prognostic factors for OS are high MATVWTB and TLGWTB values, increasing stage and male gender. TLGWTB and stage are also independent prognosticators in PFS. Only whole-body TLG is of prognostic value in NSCLC for both OS and PFS. Stratification of patients by TLGWTB might complement outcome prediction but the TNM stage remains the most important determinant of prognosis. In order to predict the outcome of patients with non-small cell lung cancer (NSCLC) the currently used prognostic system (TNM) is not accurate enough. The prognostic significance of the standard uptake value (SUV) measured by PET remains controversial. This study aims to evaluate the prognostic value in overall survival (OS) and progression free survival (PFS) of the standard uptake value (SUV), the total lesion glycolysis (TLG) and the mean metabolic active volume (MATV) in NSCLC. The study reveals that TLG of the whole-tumor burden is an independent prognostic factor for OS and PFS in patients with NSCLC.


Naratriptan for the treatment of acute migraine: meta-analysis of randomised controlled trials.
To evaluate the comparative efficacy and tolerability of naratriptan in the treatment of acute attacks of migraine. Meta-analysis of randomised controlled trials using a random effects model. A total of 4499 patients suffering from moderate or severe attacks of acute migraine reported in ten trials. Response rate ratios for headache relief, pain-free response and sustained relief (4-24 hours). Adverse events were estimated with the rate ratio (RR), risk difference and number needed to harm. Pooled RRs relative to placebo for pain-free response at 2 and 4 hours for naratriptan 2.5 mg were 2.52 (95% CI: 1.78-3.57) and 2.58 (1.99-3.35). Naratriptan 2.5 mg was more effective than naratriptan 1 mg; the corresponding RRs for pain-free response at 2 and 4 hours were 1.54 (95% CI: 1.28-1.86) and 1.35 (1.20-1.51). In contrast, naratriptan 2.5 mg was less effective in pain-free response than either rizatriptan 10 mg at 4 hours (RR: 0.68; 95% CI: 0.55-0.85) or sumatriptan 100 mg at 4 hours (RR: 0.79; 95% CI: 0.67-0.93). However, significantly fewer patients experienced adverse effects with naratriptan 2.5 mg than with rizatriptan 10 mg (RR: 0.73; 95% CI: 0.56-0.97) or sumatriptan 100 mg (RR: 0.68; 95% CI: 0.55-0.86). Naratriptan is an effective and well-tolerated treatment for acute attacks of migraine. Head-to-head comparisons suggest that naratriptan 2.5 mg is significantly more effective than the 1 mg dose. Rizatriptan 10 mg and sumatriptan 100 mg were superior to naratriptan in terms of headache relief, while zolmitriptan 2.5 mg seemed to have comparable efficacy. Randomised controlled trials have shown that at licensed doses (1 and 2.5 mg), naratriptan is associated with a lower incidence of adverse effects than rizatriptan, sumatriptan and zolmitriptan. The incidence rates of adverse effects were similar to placebo.


Structural identifiability and indistinguishability analyses of the minimal model and a euglycemic hyperinsulinemic clamp model for glucose-insulin dynamics.
Many mathematical models have been developed to describe glucose-insulin kinetics as a means of analysing the effective control of diabetes. This paper concentrates on the structural identifiability analysis of certain well-established mathematical models that have been developed to characterise glucose-insulin kinetics under different experimental scenarios. Such analysis is a pre-requisite to experiment design and parameter estimation and is applied for the first time to these models with the specific structures considered. The analysis is applied to a basic (original) form of the Minimal Model (MM) using the Taylor Series approach and a now well-accepted extended form of the MM by application of the Taylor Series approach and a form of the Similarity Transformation approach. Due to the established inappropriate nature of the MM with regard to glucose clamping experiments an alternative model describing the glucose-insulin dynamics during a Euglycemic Hyperinsulinemic Clamp (EIC) experiment was considered. Structural identifiability analysis of the EIC model is also performed using the Taylor Series approach and shows that, with glucose infusion as input alone, the model is structurally globally identifiable. Additional analysis demonstrates that the two different model forms are structurally distinguishable for observation of both glucose and insulin.


Chiropractic conservatism and the ability to determine contra-indications, non-indications, and indications to chiropractic care: a cross-sectional survey of chiropractic students.
While there is a broad spectrum of practice within chiropractic two sub-types can be identified, those who focus on musculoskeletal problems and those who treat also non-musculoskeletal problems. The latter group may adhere to the old conservative 'subluxation' model. The main goal of this study is to determine if chiropractic students with such conservative opinions are likely to have a different approach to determine contra-indications, non-indications and indications to chiropractic treatment versus those without such opinions. An anonymous and voluntary survey on 3rd to 6th year French chiropractic students was conducted between November 2017 and January 2018. Level of chiropractic conservatism (10 items) and the ability to determine contra-indications (2 cases), non-indications (4 cases) and indications (3 cases) were evaluated through a questionnaire. Answers to these cases were dichotomized into 'appropriate' and 'inappropriate' answers, as defined by previous research teams and the present team. The level of conservatism was classified into four groups, 'group 4' corresponding to the highest score. Descriptive data are provided, and bi- and multivariate analyses were performed through logistic regression to test the associations between the level of conservatism and the ability to determine the suitability of chiropractic treatment. In all, 359 of 536 (67%) students responded to the questionnaire. They generally recognized a number of contra-indications and indications to treatment. However, they found it more difficult to identify non-indications. The more conservative students were more likely to intend to treat their patients, even if this was irrelevant (non-indications). For example, those who were most conservative (group 4) were much more willing than those in group 1 to treat 'chiropractically' a 5-year-old child with no history of back pain or disease to prevent future back pain (OR = 14.7) and also to prevent non-musculoskeletal disease (OR = 22). It is concerning that students who adhere to the subluxation model are prepared to 'operationalize' their conservative opinions in their future scope of practice; apparently willing to treat asymptomatic people with chiropractic adjustments. The determinants of this phenomenon need to be understood.


Gadofosveset trisodium-enhanced MR angiography for detection of lower gastrointestinal bleeding.
The purpose of our study is to determine if Gadofosveset trisodium-enhanced magnetic resonance angiography (MRA) could be used for detection and localization of acute lower gastrointestinal (LGI) bleed. Four patients underwent MRA (4 females, mean age of 65 years) for suspected LGI bleeding. MRA detected an active rectal bleed in one patient. All other patients did not demonstrate active bleeding and these true negatives were confirmed by computed tomography angiography, endoscopy, and tagged-red blood cell scan or digital subtraction angiography. Preliminary results suggest that MRA may serve as an alternative technique for detecting acute LGI bleeding when nuclear scintigraphy is unavailable or in the younger radiosensitive population but further investigation in a larger cohort is required.


PNUTS forms a trimeric protein complex with GABA(C) receptors and protein phosphatase 1.
Phosphorylation and dephosphorylation of neurotransmitter receptors represent an important mechanism to regulate synaptic signal transduction. Here, we identified PNUTS, a targeting subunit of protein phosphatase 1 (PP1) as a new binding partner of GABA(C) receptors. In the mammalian retina, PNUTS is co-expressed with GABA(C) receptors and PP1 in bipolar cells. PNUTS and PP1 were detected in membrane protein preparations of the retina and precipitate with GABA(C) receptor specific antibodies. Furthermore, PNUTS shuttles from the nucleus to the membrane in cells co-expressing GABA(C) receptors. We show simultaneous binding of PP1 and GABA(C) receptors to different domains of PNUTS, demonstrating that PNUTS cross-links PP1 and GABA(C) receptors. Finally, modeling studies showed that the PP1 docking motif of PNUTS fits into the binding pocket on the enzyme surface, despite a C-terminal adjacent proline. We suggest that PNUTS targets PP1 to synaptic sites, acting as a temporary bridge between the phosphatase and GABA(C) receptors.


Less Than Full-time Training in surgical specialities: Consensus recommendations for flexible training by the Association of Surgeons in Training.
Changes in lifestyle, career expectations, and working environments, alongside the feminisation of the workforce have resulted in an increased demand for Less Than Full-time Training (LTFT) within surgery. However, provision of and adequacy of flexible training remain variable. It is important that LTFT options are provided to ensure surgery is an attractive and viable career option, and can compete with other specialties to attract and retain the best candidates to maintain high standards of patient care. LTFT options should be readily available to both genders within surgical specialities. Furthermore, improved information for those considering LTFT should be available, locally, regionally and nationally. Training within LTFT posts should be tailored to the training requirements of the individual, in order to achieve the competencies necessary for completion of training. The recommendations set out in this consensus statement should inform the trainee's position and help guide discussions with respect to the provision of LTFT within surgery.


25-Azavitamin D3, an inhibitor of vitamin D metabolism and action.
25-Azavitamin D3 inhibited both the bone calcium mobilization and intestinal calcium transport responses of rats to vitamin D3 but not to 25-hydroxyvitamin D3. Although 25-azavitamin D3 had no effect on the response of bone to 1alpha,25-dihydroxyvitamin D3, it did diminish the response of the intestine to that metabolite. 25-Azavitamin D3 increased liver vitamin D content and reduced the concentration of 25-hydroxyvitamin D3 required to inhibit the metabolism of vitamin D3 (75 and 200 microgram) were similar to the doses of 25-azavitamin D3 required to inhibit the action of vitamin D3 in vivo (50 and 150 microgram). 25-Azavitamin D3 is thus a vitamin D antagonist, acting for the most part via inhibition of the liver 25-hydroxylation of vitamin D3.


Research advances in prevention and treatment of burn wound deepening in early stage.
The burn wound is a dynamic living environment that is affected by many factors. It may present a progressive expansion of necrosis into the initially viable zone of stasis within a short time postburn. Therefore, how to salvage of the zone of stasis is of crucial importance in prevention and treatment strategies of burn wound progressive deepening. This review focuses on the cellular basis of tissue injury and the current progress of prevention and treatment strategies of burn wound progressive deepening, in order to provide references for the treatment of burn wounds in the early phase.


Effects on Consumers' Subjective Understanding and Liking of Front-of-Pack Nutrition Labels: A Study on Slovenian and Dutch Consumers.
In the context of the ongoing debate on front-of-pack labels (FOPL), extant research highlights a lack of clear indications on which label is most effective in increasing consumers' knowledge of food nutritional quality, and in favoring informed food choices. In this study, we have compared the effects of two different labels, one nutrient-specific label (i.e., NutrInform Battery) and one summary label (i.e., Nutri-Score), in terms of consumers' "subjective understanding" and "liking". Our work advances prior research on FOPL performance by focusing on two different countries-which have different socio-political contexts and which, from previous studies, present limited evidence on the topic-Slovenia, currently utilizing the Protective Food logo, and the Netherlands, who has recently adopted the Nutri-Score. The study also confirms, in line with previous research, a higher effectiveness of the nutrient-specific label, NutrInform Battery, on all analyzed dimensions in tested countries, when compared to the summary label, Nutri-Score.


Health and sanitary status in 1970 of Tubu nomads dwelling in Northeastern Niger.
The Tubu are nomadic people who live in remote parts of the central Sahara, primarily in the Tibesti massif (Chad), and in both Northeastern Niger and Southern Libya. No data about the Tubu's health and sanitary status are currently available. In 1970, the "Mission Anthropologique Belge au Niger" (MABN) investigated a Tubu tribe named Broaya that lived on the northeastern rim of the Tenere desert. One hundred and fifty-one adult volunteers were investigated. The environmental fauna of medical importance was also studied. Albeit 43 year-old, these results have not been previously published. The estimated age of death for fathers was approximately 56 years, and that for mothers was 60 years. The overall perinatal mortality rate was 232%, the overall infant mortality rate was 153%, and the overall child mortality rate was 99%. The physical examination found 6 cases of blindness (4.0%). Five subjects presented with an elevated blood pressure (3.3%), and 5 (3.3%) displayed an abnormal thoracic auscultation evocative of tuberculosis or of an acute lung infection. In the field, no blood-fluke eggs were found in the urine samples. The blood thin films and stool samples were preserved then subsequently examined in Toulouse. The search for blood parasites was negative. Three subjects (2%) passed E. histolytica/E. dispar cysts in stools, 16 (10.6%) were parasitized with Giardia sp. and 4 (2.65%) were parasitized with Hymenolepis nana. Two specimens of scorpions captured in the camp were subsequently identified as belonging to the harmful genus Androctonus or Leiurus. An investigation into the freshwater fauna was conducted in the marshy ponds surrounding the ghost city of Djado, and no intermediate snail hosts for schistosomiasis haematobium were found. Larvae and nymphs, of Anopheles hispaniola and of An. multicolor, which are not efficient vectors for malaria, were collected. Infection-related blindness and trachoma, along with acute pulmonary infections and probably tuberculosis were the major health burden in this tribe. The harsh dry and hot climate may explain the low prevalence of soil-transmitted protozoan diseases or helminthiases.


Electron tomography and computer visualisation of a three-dimensional 'photonic' crystal in a butterfly wing-scale.
A combination of transmission electron tomography and computer modelling has been used to determine the three-dimensional structure of the photonic crystals found in the wing-scales of the Kaiser-I-Hind butterfly (Teinopalpus imperialis). These scales presented challenges for electron microscopy because the periodicity of the structure was comparable to the thickness of a section and because of the complex connectivity of the object. The structure obtained has been confirmed by taking slices of the three-dimensional computer model constructed from the tomography and comparing these with transmission electron microscope (TEM) images of microtomed sections of the actual scale. The crystal was found to have chiral tetrahedral repeating units packed in a triclinic lattice.


[Prevention of suppurative complications considering the risk of their occurrence].
The efficacy of a mark-grading system for the prognosis of the occurrence of suppuration in acquired and congenital heart diseases is analyzed in this work. The mathematical relationship between the sum of marks of the risk and the probability of the occurrence of purulent complication is proved. On the grounds of the found phenomenon a group of patients with high risk of purulent complications, needing some supplementary prophylactic procedures, has been selected. A complex of medicamental and organizational measures has been devised, which ensured more than 1.5-fold decrease of the incidence of surgical infection in high risk patients following operations with extracorporeal circulation.


Serum levels of soluble PD1 in pemphigus vulgaris: A useful marker for disease severity.
Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering disease targeting the skin and mucous membranes. Programmed cell death protein 1 (PD1) is an immune checkpoint which binds to two ligands, PDL1 and PDL2 resulting in negative regulation of antigen receptor signaling, thus, play a critical role in the immune regulation of autoimmune diseases. In this work we aimed to assess serum levels of soluble PD1 (sPD1) in patients with active PV and in patients in remission in an attempt to evaluate its effect on disease severity. In this case-control study, 60 pemphigus vulgaris patients (30 clinically active and 30 in a clinical remission) and 30 age matched healthy control subjects were included. Severity of PV was assessed using pemphigus disease area index (PDAI) score. Serum levels of sPD1 were measured by ELISA for both patients and healthy control. Serum levels of sPD1 were significantly lower in PV patients than in controls (P < .001) and significantly lower in patients with active disease than in those in remission (P < .001). Serum sPD1 correlated negatively with the severity of the disease (P < .001, r = -0.4). A defect in PD1 pathway is suggested in PV patients, and this defect plays a substantial role in determining the severity of the disease. Thus, sPD1 could be considered a useful marker for disease severity and targeting PD1 pathway could be a potential aim for future therapies of PV.


The use of somatic antigen of Haemophilus influenzae for the monitoring of T cell-mediated skin test reactivity in man.
To investigate its usefulness as a skin test antigen, Haemophilus influenzae somatic antigen was tested in 28 healthy individuals, both in soluble and aggregated form. All subjects were found to possess specific antibodies against H. influenzae of both IgG and IgM subclass, thus showing their previous exposure to this commensal micro-organism. The somatic antigen in solution was found to be a poor antigen for eliciting a delayed hypersensitivity skin response: only 2 out of 16 subjects reacted with a positive DTH pattern. In contrast, 25 out of 28 persons showed a positive DTH pattern when somatic antigen was used in aggregated form. Two types of DTH reaction patterns could be detected (in a ratio of approximately 3:2), viz. those with an early (24 h) and those with a late (48 h) maximal swelling. Histology of 3 early and 1 late DTH reaction showed perivascular infiltrates of mainly Thelper/Tinducer lymphocytes. Hardly any basophils were seen. One negative skin test, biopsied at 6 h, showed no signs of Arthus reactivity. It can be concluded that skin tests using the aggregated form of the somatic antigen of H. influenzae are useful for assaying specific T-cell-mediated reactivity in man.


Eosinophilic gastroenteritis presenting as ileocolitis.
An adolescent girl who presented with clinical and roentgenographic ileocolitis diagnosed as Crohn's disease was found to have histological evidence of eosinophilic gastroenteritis. The potential for colonic involvement in this disease is affirmed.


Designer D-form self-assembling peptide nanofiber scaffolds for 3-dimensional cell cultures.
Traditional 2-D cell cultures have many limitations because they do not truly mimic the natural environment. In order to fully understand the in vivo 3-D environment, it is crucial to develop a biomimetic 3-D culture system. Recently progress toward 3-D tissue cell cultures has been gradually made by addressing many critical issues including the microenvironment, gradient diffusion and apoptosis. Here we report a D-form self-assembly peptide system that provides insight into the relationships between nanofiber scaffolds and cell behaviors in 3-D cell cultures. We observed the peptide secondary structures response to ions and confirmed that their participation increases mechanical force rapidly. We also showed the enzymes attachment to nanofibers, investigated scaffolds to form 3-D microenvironment and described a modified protocol for 3-D cell culture D-form self-assembly peptide. Using this protocol, we showed cell behavior in the D-form peptide with high cell viability and low-level cell apoptosis for weeks. Furthermore, we proposed a plausible model for chiral self-assembly peptides in 3-D culture. Our research may further stimulate others to design novel biological materials at single chiral amino acid level, and may broaden the applications of designer D-form self-assembling peptides in clinical and medical nanobiotechnology.


Antithrombotic therapy in the secondary prevention of myocardial infarction.
There is now convincing evidence that the majority of myocardial infarcts are caused by acute occlusion of the coronary artery with a thrombus, often originating from a ruptured atherosclerotic plaque. The thrombus is composed of both platelets and fibrin, so it is logical to expect that both antiplatelet and anticoagulant therapy would be effective for the prevention of reinfarction and other thrombotic vascular events following myocardial infarction. A review of clinical trials confirms this suggestion. Aspirin is beneficial in that it reduces vascular mortality by about 12% and total vascular events by 25%. Similarly, oral anticoagulants reduce total mortality by up to 20% and vascular events by about 40%. However, relatively few large scale trials of oral anticoagulants after infarction have been carried out, and the confidence intervals are wider than those for the aspirin trials. In practice aspirin is used more widely than oral anticoagulants as it is easier to administer and control. Only one trial (EPSIM) has directly compared oral anticoagulants and aspirin. This trial showed that both drugs had equal efficacy but that compliance with aspirin was better. Finally, the question of giving antiplatelet agents and anticoagulants together, to block both platelet aggregation and fibrin formation, is considered. A preliminary trial in prosthetic heart-valve patients has been encouraging but more large, long-term trials are required before recommendations can be made, as the use of both drugs together carries an increased risk of severe hemorrhage.


Update and validation of the lifetime cardiovascular risk in Spain: IBERLIFERISK2.
The function to estimate lifetime cardiovascular risk -IBERLIFERISK- in Spanish working population, obtained a satisfactory discrimination; however, there was a slight overestimation of the risk in men and an underestimation of the risk in women. To recalibrate the current lifetime risk equation after extending the follow-up by 3 years. Retrospective cohort study. 762.058 workers who underwent an occupational health examination between 2004 and 2007 were included. All episodes of temporary sickness and cardiovascular mortality up to December 2017 were evaluated. Regression models were combined to take into account the presence of competing risks in estimating cardiovascular risk in the derivation cohort. Calibration was performed by graphically representing the proportion of expected and observed events at 10 years of follow-up in the validation cohort, stratifying by risk deciles and calculating the Spiegelhalter Z statistic. Discrimination was evaluated graphically using the Receiver Operating Curve (ROC) and calculating Harrell's C index. The mean age was 35.48 years (SD 10.56). 71.14% were men. Harrell's C index was 0.78 (95% CI 0.76-0.79) in men and 0.73 (95% CI 0.69-0.77) in women. In general, there was a slight degree of underestimation in women and overestimation in men in the last decile of risk, although the Spiegelhalter Z statistic was not statistically significant in both sexes (p>0.05). The updated model continues to discriminate satisfactorily, although the model's calibration has not substantially improved with the new update.


Metal content in caviar of wild Persian sturgeon from the southern Caspian Sea.
Caviar (fish roe of sturgeon) may contain high levels of contaminants. An inductively coupled plasma-optical emission spectrometer and a direct mercury analyzer were used to assess the contents of four heavy metals (Hg, Se, Sn, and Ba) in caviar of wild Persian sturgeon sea foods. The levels of Hg ranged from 1.39 to 1.50 μg g(-1), Se from 0.90 to 1.10 μg g(-1), Sn from 0.23 to 0.33, and Ba from 0.71 to 1.17 µg g(-1). Evaluation of these levels showed that except for Hg, the average concentrations of other metals are significantly lower than adverse level for the human consumption when compared with Food and Agricultural Organization of the United Nations and World Health Organization permissible limits. Therefore, their contribution to the total body burden of these heavy metals can be considered as negligibly small given that caviar is a luxury product.


Pre-operative albendazole therapy for hydatid cyst.
Surgical management of hydatid cyst is associated with recurrence in 10 per cent of patients. The role of perioperative chemotherapy in prevention of recurrence has not been extensively explored. Sixteen patients with Echinoccus granulosus were treated with albendazole 10 mg kg-1 before operation; of fourteen patients who received albendazole for 1 month or more before operation only one (with doubtful therapeutic compliance) had viable protoscoleces, in contrast both of the two remaining patients who received only 1 and 3 weeks therapy had live disease at the time of operation. A 1 month pre-operative course of albendazole kills most if not all protoscoleces within hydatid cysts in man. This may allow pre-operative 'sterilization' of cysts and a reduction in the risk of recurrence.


Aquirufa lenticrescens sp. nov. and Aquirufa aurantiipilula sp. nov.: two new species of a lineage of widespread freshwater bacteria.
Two bacterial strains, 9H-EGSET and 15D-MOBT, were isolated from small freshwater habitats located near Salzburg, Austria. They showed the highest 16S rRNA sequence similarities of 100% and 99.9%, respectively, with type strains of species of the genus Aquirufa (Bacteroidota). Genome-based phylogenetic reconstructions with 119 amino acid sequences assigned the new taxa to the two distinct branches of the genus Aquirufa. Whole-genome average nucleotide identities were calculated with all possible pairs belonging to the genus. Values between 75.4% and 88.6% revealed that the two new strains represent each a new species. Like all, so far described members of the genus, they grew aerobically and chemoorganotrophically, were rod-shaped, red-pigmented, and motile by gliding, and showed genome sizes of about 3 Mbp and G + C values of about 40%. They could be distinguished by some phenotypic and chemotaxonomic features from their nearest related species. Until now, strain 9H-EGSET is the only one among the Aquirufa strains which contained traces of MK8 as respiratory quinone, and strain 15D-MOBT is the only one that formed tiny orange globules in liquid medium. The genome of strain 9H-EGSET comprised genes for the complete light-harvesting rhodopsin / retinal system, in the case of 15D-MOBT genes predicted for a nitrous oxide reductase were present. For the two new species of the genus Aquirufa, we propose to establish the names Aquirufa lenticrescens for strain 9H-EGSET (= JCM 34077 T = CIP 111926 T) and Aquirufa aurantiipilula for strain 15D-MOBT (= JCM 34078 T = CIP 111925 T).


Alternative methods of diagnosis and staging of bladder cancer.
A survey of the conventional diagnostic measures in bladder carcinoma is given. The importance of additional methods, such as pelvic arteriography and phlebography, lymphography and lymphoscanning is evaluated.


Response of nitrogen-fixing water fern Azolla biofertilization to rice crop.
The water fern Azolla harbors nitrogen-fixing cyanobacterium Anabaena azollae as symbiont in its dorsal leaves and is known as potent N2 fixer. Present investigation was carried out to study the influence of fresh Azolla when used as basal incorporation in soil and as dual cropped with rice variety Mahsoori separately and together with and without chemical nitrogen fertilizer in pots kept under net house conditions. Results showed that use of Azolla as basal or dual or basal plus dual influenced the rice crop positively where use of fern as basal plus dual was superior and served the nitrogen requirement of rice. There was marked increase in plant height, number of effective tillers, dry mass and nitrogen content of rice plants with the use of Azolla and N-fertilizers alone and other combinations. The use of Azolla also increased organic matter and potassium contents of the soil.


Cefiderocol for treatment of an empyema due to extensively drug-resistant Pseudomonas aeruginosa: Clinical observations and susceptibility testing considerations.
Cefiderocol is a novel siderophore cephalosporin antibacterial with activity against carbapenem-resistant Gram-negative bacteria including Pseudomonas aeruginosa. We report a medically complex patient treated with compassionate use cefiderocol for an empyema caused by extensively drug-resistant P. aeruginosa as well as clinical considerations for cefiderocol use based on our findings. We observed a potential discordance in cefiderocol susceptibility testing results depending if disk diffusion or iron-depleted cation-adjusted Mueller Hinton Broth dilution is used. Furthermore, interpretative criteria differ between the Clinical Laboratory Standards Institute and United States Food and Drug Administration for P. aeruginosa, which makes cefiderocol interpretation potentially challenging for clinicians. We may have also observed selective pressure from prior cefiderocol exposure given the respective increases and decreases in MIC values and zone diameters for P. aeruginosa isolates following cefiderocol treatment. Additional data are needed to further describe cefiderocol use, susceptibility testing, and resistance development as real-world clinical use expands.


[The vasa vasorum of peripheral lymph vessels in the human].
Using the anterior inner prefascial bundle as an example the structure of the vasa vasorum of lymphatic vessels can be demonstrated. They have a one-dimensional capillary network of their own in the outer layers of the vascular wall. In humans this network is already differential in the second half of the fetal period.


Putting the Pieces in Place: Mobilizing Cellular Players to Improve Annulus Fibrosus Repair.
The intervertebral disc (IVD) is an integral load-bearing tissue that derives its function from its composite structure and extracellular matrix composition. IVD herniations involve the failure of the annulus fibrosus (AF) and the extrusion of the nucleus pulposus beyond the disc boundary. Disc herniations can impinge the neural elements and cause debilitating pain and loss of function, posing a significant burden on individual patients and society as a whole. Patients with persistent symptoms may require surgery; however, surgical intervention fails to repair the ruptured AF and is associated with the risk for reherniation and further disc degeneration. Given the limitations of AF endogenous repair, many attempts have been made toward the development of effective repair approaches that reestablish IVD function. These methods, however, fail to recapitulate the composition and organization of the native AF, ultimately resulting in inferior tissue mechanics and function over time and high rates of reherniation. Harnessing the cellular function of cells (endogenous or exogenous) at the repair site through the provision of cell-instructive cues could enhance AF tissue regeneration and, ultimately, improve healing outcomes. In this study, we review the diverse approaches that have been developed for AF repair and emphasize the potential for mobilizing the appropriate cellular players at the site of injury to improve AF healing. Impact statement Conventional treatments for intervertebral disc herniation fail to repair the annulus fibrosus (AF), increasing the risk for recurrent herniation. The lack of repair devices in the market has spurred the development of regenerative approaches, yet most of these rely on a scarce endogenous cell population to repair large injuries, resulting in inadequate regeneration. This review identifies current and developing strategies for AF repair and highlights the potential for harnessing cellular function to improve AF regeneration. Ideal cell sources, differentiation strategies, and delivery methods are discussed to guide the design of repair systems that leverage specialized cells to achieve superior outcomes.


Multiple coronary artery fistulae with biventricular hypertrophy.
Here, we report a case of multiple coronary artery fistulae with biventricular hypertrophy. The initial diagnosis of multiple coronary artery fistulae, draining into the left as well as the right ventricle, was made by standard transthoracic 2-dimensional and Doppler echocardiography. Later, multiple coronary fistulae communicating with the left ventricle through persistent sinusoids were diagnosed by coronary angiography.


Choosing the Active X: The Human Version of X Inactivation.
Humans and rodents differ in how they carry out X inactivation (XI), the mammalian method to compensate for the different number of X chromosomes in males and females. Evolutionary changes in staging embryogenesis and in mutations within the XI center alter the process among mammals. The mouse model of XI is predicated on X counting and subsequently choosing the X to 'inactivate'. However, new evidence suggests that humans initiate XI by protecting one X in both sexes from inactivation by XIST, the noncoding RNA that silences the inactive X. This opinion article explores the question of how the active X is protected from silencing by its own Xist locus, and the possibility of different solutions for mouse and human.


Extracorporeal membrane oxygenation as a bridge vs. non-bridging for lung transplantation: A systematic review and meta-analysis.
Whether extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation (BTT) can achieve a similar survival to non-BTT remains controversial. We conducted this meta-analysis to compare the outcomes between ECMO BTT and non-BTT to facilitate better clinical decision-making. Seven databases were searched for eligible studies comparing ECMO BTT and non-BTT. The primary endpoints included survival, intraoperative indicators, postoperative hospitalization indicators, and postoperative complications. Nineteen studies (involving 7061 participants) were included in the final analysis. The outcomes of overall survival, overall survival rate, graft survival rate, in-hospital mortality, postoperative hospital days, postoperative intensive care unit days, postoperative ventilation time, blood transfusion volume, and postoperative complications were all better in the non-BTT group. The total mortality in ECMO bridging was 23.03%, in which the top five causes of death were right heart failure (8.03%), multiple organ failure (7.03%), bleeding (not cranial) (4.67%), cranial bleeding (3.15%), and sepsis (2.90%). In summary, Non-BTT is associated with better survival and fewer complications compared to BTT. When ECMO may be the only option, the patient and medical team need to realize the increased risk of ECMO by complications and survival.


The importance of the margin of resection and external radiation in non-lipomatous retroperitoneal sarcoma.
Prior studies evaluating the impact of adjuvant or neoadjuvant radiation on clinical outcomes of patients with non-lipomatous retroperitoneal sarcoma have been underpowered. We queried the National Cancer Database to identify patients undergoing surgical resection of retroperitoneal sarcoma with non-lipomatous histology from 2004 to 2016. Multivariable logistic regression and Cox proportional hazards modelling with patients stratified by tumor size were used to identify factors associated with overall survival. 3,394 patients met inclusion criteria. 592 had small (<5 cm), 1,186 had intermediate (5-10 cm), and 1,616 had large (>10 cm) tumors. Use of either neoadjuvant or adjuvant radiotherapy was associated with improved survival for patients with intermediate (neoadjuvant HR 0.67, CI [0.46, 0.98]; adjuvant HR 0.61, CI [0.50, 0.76]) and large (neoadjuvant HR 0.50, CI [0.37, 0.68]; adjuvant HR 0.56, CI [0.47, 0.69]) tumors, while adjuvant radiation therapy was associated with a survival benefit for small-sized tumors (HR 0.67, CI [0.46, 0.99]). Radiation therapy is associated with an overall survival benefit in patients presenting undergoing resection of non-lipomatous retroperitoneal sarcoma.


Effect of water stress by Polyethylene Glycol 8000 and Sodium Chloride on germination of Ephedra alata Decne seeds.
Ephedra alata Decne is a perennial shrub and it is a very effective sand-binder. In Saudi Arabia, the species is associated with sand dunes formation, especially the mobile, non-saline and low moisture content ones. Its geographical distribution in Saudi Arabia includes the Northern, Eastern and Central regions. The aims of this study were to determine the effects of temperature, water potential and Sodium Chloride on germination of E. alata. Seeds were collected from King Khalid Centre of Wildlife Research and Development at Thumama (80 km north east of Riyadh), Saudi Arabia. Seeds were germinated at four alternating temperature regimes (8/22; 9/23; 13/27 and 18/35 °C). Seeds were also germinated under stress of aqueous Polyethylene Glycol (PEG) solutions mixed to create water potentials of 0; -0.3; -0.6; -1.2 and -1.5 MPa. Seed were also germinated in Sodium Chloride solutions of 0, 0.05, 0.1, 0.2 and 0.3 mol l(-1). Optimum germination was attained at 13/28 °C that corresponds to temperatures prevailing during spring time. Seeds germinated in Polyethylene Glycol solutions exhibited significantly lower germination than control especially when water potential fell below -0.3 MPa. Germination was also negatively affected by 0.1 mol l(-1) Sodium Chloride solution or above. Results indicated that the germination temperature responses of the nondormant seeds synchronize the event of germination with the season when environmental conditions are more favorable for subsequent growth and seedling establishment. Germination was also sensitive to both water potential and salinity.


Preferential induction of fetal versus embryonic globin chains in human leukemic cell lines.
By use of a newly developed technique combining affinity chromatography of hemoglobin on haptoglobin-Sepharose and IEF of globin chains, we analyzed the globin synthetic pattern of human K562 cells in both the basal state and after addition of several potential inducers. Hemin only was found effective: its addition at 50 microM results in a quantitative increase of globin chain synthesis (from 0.3 to 1% up to 5%) and a qualitative "switch" with a striking increase of alpha and a decrease of epsilon and zeta chains (relative to the prevailing gamma chains). This system, in which hemin induces changes that mimic to some extent the normal embryonic-fetal switch, might therefore provide a cellular model for investigating molecular mechanisms of globin gene regulation. In addition similar results were obtained with a different human myeloid leukemia cell line, the KG1, thus raising the possibility that the expression of embryonic globin genes in malignant cells might not be simply the consequence of abnormal gene expression but rather reflect a possibly physiological differentiation phenomenon.


The Diels-Alder reaction: A powerful tool for the design of drug delivery systems and biomaterials.
Click reactions have the potential to greatly facilitate the development of drug delivery systems and biomaterials. These reactions proceed under mild conditions, give high yields, and form only inoffensive by-products. The Diels-Alder cycloaddition is one of the click reactions that do not require any metal catalyst; it is one of the most useful reactions in synthetic organic chemistry and material design. Herein, we highlight possible applications of the Diels-Alder reaction in pharmaceutics and biomedical engineering. Particular focus is placed on the synthesis of polymers and dendrimers for drug delivery, the preparation of functionalized surfaces, bioconjugation techniques, and applications of the Diels-Alder reaction in nanotechnology. Moreover, applications of the reaction for the preparation of hydrogels for drug delivery and tissue engineering are reviewed. A general introduction to the Diels-Alder reaction is presented, along with a discussion of potential pitfalls and challenges. At the end of the article, we provide a set of tools that may facilitate the application of the Diels-Alder reaction to solve important pharmaceutical or biomedical problems.


Design of a Ka-Band Five-Bit MEMS Delay with a Coplanar Waveguide Loaded U-Shaped Slit.
This paper designs a five-bit microelectromechanical system (MEMS) time delay consisting of a single-pole six-throw (SP6T) RF switch and a coplanar waveguide (CPW) microstrip line. The focus is on the switch upper electrode design, power divider design, transmission line corner compensation structure design, CPW loading U-shaped slit structure design, and system simulation. The switch adopts a triangular upper electrode structure to reduce the cantilever beam equivalent elastic coefficient and the closed contact area to achieve low drive voltage and high isolation. The SP6T RF MEMS switch uses a disc-type power divider to achieve consistent RF performance across the output ports. When designed by loading U-shaped slit on transmission lines and step-compensated tangents at corners, the system loss is reduced, and the delay amount is improved. In addition, the overall size of the device is 2.1 mm × 2.4 mm × 0.5 mm, simulation results show that the device has a delay amount of 0-60 ps in the frequency range of 26.5-40 GHz, the delay accuracy at the center frequency is better than 0.63 ps, the delay error in the whole frequency band is less than 22.2%, the maximum insertion loss is 3.69 dB, and the input-output return rejection is better than 21.54 dB.


Long-term storage of blood samples at freezing temperatures in the presence of a cryoprotectant for hemiglobin assay.
Changes in Hi levels in experimentally prepared blood samples during storage at various temperatures were studied. When whole blood in which Hi levels were elevated by sodium nitrite was stored unfrozen, rapid reduction of Hi was observed within 24 hr even at 0 degrees C. When whole blood or a diluted hemolysate was stored frozen for a week or longer, considerable formation of Hi by autoxidation was observed, the formation at -20 degrees C being much more significant than that at -30 degrees C. On the other hand, addition of an equal volume of the cryoprotectant solution of Rowe et al. to blood almost completely inhibited this Hi formation during freezing storage until at least 30 days. Thus, a new method for long-term storage of blood samples for Hi assay was devised.


Why is Mg2+ necessary for specific cleavage of the terminal phosphoryl group of ATP?
The mechanism of specific cleavage of the terminal phosphoryl group in hydrolysis of ATP, and the role of Mg2+ in the hydrolysis were studied by ab initio molecular orbital calculations. The tetravalent anion of methyl triphosphate was used as a model of the ATP anion, and its electronic structures were determined as a function of the distance between Mg2+ and its beta-phosphoryl group. We found that the closer location of Mg2+ to the beta-phosphoryl group than to the alpha- or gamma-phosphoryl group was effective in weakening the P-O bond at which the cleavage of ATP catalyzed by most enzymes takes place. Moreover, the orbital coefficient of the frontier electron of P gamma, which is related to the nucleophilic reaction, was shown to increase greatly with increasing interaction between Mg2+ and the beta-phosphoryl group.


Overexpression of the long non-coding RNA MEG3 impairs in vitro glioma cell proliferation.
Gliomas are the most common type of primary brain tumor in the central nervous system of adults. Maternally Expressed Gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes a non-coding RNA (ncRNA) associated with tumorigenesis. However, little is known about whether and how MEG3 regulates glioma development. In the present study we assayed the expression of MEG3 in glioma tissue samples by real-time polymerase chain reaction assay, and defined the biological functions and target genes by CCK-8 assay, flow cytometry, and RNA immunoprecipitation. We first demonstrated that MEG3 expression was markedly decreased in glioma tissues compared with adjacent normal tissues. Moreover, ectopic expression of MEG3 inhibited cell proliferation and promoted cell apoptosis in U251 and U87 MG human glioma cell lines. We further verified that MEG3 was associated with p53 and that this association was required for p53 activation. These data suggest an important role of MEG3 in the molecular etiology of glioma and implicate the potential application of MEG3 in glioma therapy.


Recommendations for Multimodality Cardiovascular Imaging of Patients with Hypertrophic Cardiomyopathy: An Update from the American Society of Echocardiography, in Collaboration with the American Society of Nuclear Cardiology, the Society for Cardiovascular Magnetic Resonance, and the Society of Cardiovascular Computed Tomography.
Hypertrophic cardiomyopathy (HCM) is defined by the presence of left ventricular hypertrophy in the absence of other potentially causative cardiac, systemic, syndromic, or metabolic diseases. Symptoms can be related to a range of pathophysiologic mechanisms including left ventricular outflow tract obstruction with or without significant mitral regurgitation, diastolic dysfunction with heart failure with preserved and heart failure with reduced ejection fraction, autonomic dysfunction, ischemia, and arrhythmias. Appropriate understanding and utilization of multimodality imaging is fundamental to accurate diagnosis as well as longitudinal care of patients with HCM. Resting and stress imaging provide comprehensive and complementary information to help clarify mechanism(s) responsible for symptoms such that appropriate and timely treatment strategies may be implemented. Advanced imaging is relied upon to guide certain treatment options including septal reduction therapy and mitral valve repair. Using both clinical and imaging parameters, enhanced algorithms for sudden cardiac death risk stratification facilitate selection of HCM patients most likely to benefit from implantable cardioverter-defibrillators.


Leptin and the pituitary.
In 1994, Zhang et al. of Rockefeller University in New York reported the first successful complementary DNA (cDNA) cloning of leptin by the positional cloning method. Leptin was identified as the gene of ob/ob mouse in genetic obesity syndromes. It has very strong food intake control, and body weight and energy expenditure. The name "leptin" derived from the Greek word leptos, meaning "thin." We hereby review major advances leading to our current finding of leptin, leptin receptor and its structure, the outline of homozygote, and also influence of leptin in the pituitary. (The structure of leptin) The mouse obese gene has been localized to chromosome 6. With human leptin gene on chromosome 7q31.3, its DNA has more than 15000 base pairs and consists of three exons and two introns. For bioactivation of leptin the importance of disulfide-binding site is suggested. Human leptin which replaced the 128-th arginine with glutamine has the function of an aldosteron antagonist, which is reported to have the function of athrocytosis inhibition. The resemblance of leptin precursor of human, mouse and rat is very high, i.e., mouse and rat homology is 96% and mouse and human homology is 83%. (The structure of leptin receptor) The mutant gene, which is the cause of obesity, was shown on map on diabetic mouse (db/db) chromosome 4, and it was proven to be the same as the leptin receptor gene cloned by Tartaglia et all. Further studies have found the Zucker fatty rat (fa/fa) to be incorporated into a linkage map of rat chromosome 5, whose region of rat is the equivalent to the region of conserved synteny of the db/db mouse gene. The leptin receptor is glycoprotein consisting of a single transmembrane-spanning component. The primary structure of leptin receptor belongs to the cytokine-class1 family, the single membrane-spanning receptor, and is highly related to the gp130 signal-transducing component of the interleukin-6 (IL-6) receptor, the granulocyte colony-stimulating factor (G-CSF) receptor, and the leukemia inhibitory factor (LIF) receptor. The leptin receptor is known to have at least six existing isoforms (Ob-Ra, b, c, d, e, f) from the difference in splicing. (Homozygote Mutation of Leptin and Leptin Receptor :Hormone Secretion Disorders) The point mutation of ob/ob mouse and the splicing mutation of db/db mouse show remarkable obesity and hyperphagia. These obesity models show a reproduction disorder with both the male and the female, and they develop with homozygote. The cause is thought to be the gonadotropin secretory abnormality in pituitary. Three family lines report the cases of this deficiency, and it is considered that the secretory abnormality in pituitary develops into hypogonadotropic. These patients show low value in plasma FSHbeta (follicle stimulating hormone-beta and LHbeta (luteinizing hormone-beta which are produced from pituitary, and the plasma GnRH (gonadotropin releasing hormone) level is also low. Furthermore, the leptin receptor deficient family line was reported in 1998, in which case only the homozygote developed. The plasma leptin concentration of normal human is about 8.0 ng/ml, and this case with leptin receptor deficiency has high value of 500-700 ng/ml, which is the equivalent to the db/db mouse. (Role of Leptin in Hypothalamus-Pituitary-Periphery Function) The role of leptin which regulates pituitary hormones suggests the promotion the GHRH (growth hormone releasing hormone) secretion in hypothalamus-pituitary axis, with the possibility of the rise in secretion of GH (growth hormone) in pituitary, i.e. effects of icv (intracerebroventricular) infusion of leptin has spontaneously stimulated GHRH, which promotes GH secretion in the normal rats. On the other hand, topical treatment of GH3 (derived from a rat pituitary GH-secreting cell line) with leptin directly inhibits cell proliferation. The obesity model animals (ob/ob, db/db, fa/fa) have equally plump body compared to the normal models, which shows signs of sufficient growth. (Localization and Functional Relevance of Leptin and Leptin Receptor in Rodents Pituitary) Aside from being the food intake inhibitor and the energy control factor, leptin takes part in controlling the pituitary hormones. Promoting the secretion of GH, PRL (prolactin), TSHbeta (thyroid stimulating hormone-beta, FSHbeta/LHbeta, and inhibiting the secretion of ACTH (adrenocorticotropic hormone) are the major changes of pituitary hormones which are brought on by leptin. The expressive localization is specific, and immunohistochemistry (IHC) method recognized leptin in granular state in FSHbeta, LHbeta and TSHbeta positive cells. In our biochemical examination, the bulk of the expression of leptin is recognized in fraction of the secretory granule. In particular, FSHbeta cells had the highest percentage rate of colocalized leptin in rat pituitary. On the other hand, leptin receptor has been reported to be found only in normal rat pituitary, human pituitary adenoma, and respective cell lines in pituitaries by the RT-PCR method until now, but we disclosed for the first time the localization of leptin receptor on the plasma membrane of GH-secreting cells with the IHC method that has not been cleared so far. These findings show that leptin and leptin receptor have been expressed in different cells, and that the rat pituitary glands entertain paracrine mechanism between leptin (FSHbeta/LHbeta cells) and leptin receptor (GH cells). The function of paracrine in this pituitary suggests a new point of view in hypothalamus-pituitary axis, and it shall be concerned with many aspects such as hormone secretions and proliferation/inhibition. (Human Pituitary Adenoma) Preliminary report of leptin and leptin-receptor relationship with pituitary adenoma that has secretion abnormality has been filed, and its manifestation is being observed by the RT-PCR. Leptin and leptin receptor are expressed in most adenoma, and it is thought to function by autocrine and paracrine pathway in the adenomas. Leptin has been located in ACTH-secreting adenoma most frequently, especially in ACTH carcinoma. The leptin receptor is detected in all adenomas with high percentage rate, with both long and short forms, and then many cases of nonfunctioning pituitary adenomas, compared with other adenomas, have been reported to be positive with both long and short forms of leptin receptor as detected by RT-PCR. The HP75 cell line is derived from the nonfunctioning pituitary adenoma, which produces FSHbeta and LHbeta. The expression of leptin receptor in nonfunctioning pituitary adenoma, and the suppression of HP75 multiplication may lead to the possible hypothesis of leptin becoming one factor for the treatment of pituitary adenoma, especially in gonadotropin adenomas.


Turbulence barrier effect during heavy haze pollution events.
Under low wind speed conditions, the frequent intermittent turbulence phenomenon in the atmospheric boundary layer (ABL) greatly weakens the turbulent diffusion of pollutants to cause the heavy haze events. Turbulence may disappear at certain heights forming a laminar flow as if there is a barrier layer hindering the transmission up and down during the heavy haze periods. The turbulent data at five layers and PM2.5 (fine particular matter with a diameter smaller than 2.5 μm) concentration at two levels were used to discuss the barrier that is called the barrier effect vividly. The results revealed that the changes in the PM2.5 concentration at different heights corresponded excellently with the change in vertical turbulence barrier effect. This work explains the physical mechanism responsible for the accumulation of pollutants in heavy pollution events and the influence of turbulent diffusion conditions on the distribution of the PM2.5 concentration.


Identification of HbHSP90 gene family and characterization HbHSP90.1 as a candidate gene for stress response in rubber tree.
Heat shock protein 90 (HSP90), an essential molecular chaperone, is triggered in response to stress situations in plants. However, the roles of HSP90 gene family members in rubber tree have not been totally specified. In this study, 7 HbHSP90 genes were identified from rubber tree genome. Classification of HbHSP90 family genes into three groups, namely A, B, and C was based on phylogenetic analysis. The structural and motif analyses showed similar structural features in the same group of HbHSP90 members, but differences between groups. Analysis of cis-regulatory element sequences of HbHSP90 genes indicates that the HbHSP90 gene promoter is rich in drought, temperature, and hormone elements. qRT-PCR analysis showed that the 7 HbHSP90 genes responded in different degrees to temperature, drought and powdery mildew infection, and in particularly, HbHSP90.1 was differentially expressed under both abiotic and biotic stresses. Meanwhile, HbHSP90.1 gene was significantly expressed under the treatment of different phytohormone and H2O2 (Hydrogen Peroxide) treatments, which means that HbHSP90.1 gene performs an essential part in the growth and development of rubber trees. Furthermore, the protein interaction results showed that HbHSP90.1 interacted with HbSGT1b. Subcellular localization showed that both HbHSP90.1 and HbSGT1b located in the nucleus. Taken together, we speculate that HbHSP90.1 interacts with HbSGT1b in the nucleus to respond to rubber tree stress processes. The results of this study provide a solid foundation for further studies on the mechanism of HbHSP90 family genes in the stress resistance response of rubber tree.


The resource balance of Milium effusum with emphasis on environmental resource supply.
Growth of the broad-leaved graminoid Milium effusum, occurring in shady deciduous forests, was matched with periods of high light influx through the tree canopy in spring and autumn. Fertile shoots grew faster than sterile shoots. Leaves on flowering shoots were fully developed when the budbreak started on the trees, whereas nonflowering shoots had fully developed leaves when the tree canopy closed. Leaf concentrations of N and P were high (6.1 and 0.74% respectively) in spring but decreased as the leaves expanded. Maximum pool sizes of N and P in whole tillers were reached about one month after the onset of spring growth, whereas maximum spring pools of K, Mg, and Ca were timed with peak biomass about one month later. The leaves lost nutrients during summer when no growth took place. Since leaching losses were negligible, nutrients were probably allocated from the leaves to support root growth. Autumn reallocation to winter stores was low. The pattern of growth and nutrient use suggests that light availability, i.e., the resource in relatively lowest supply, regulates the investment of the resource in highest supply, i.e., nutrients. This is consistent with previously reported observations on Eriophorum vaginatum, a graminoid of low nutrient - high light environments. This species utilizes nutrients efficiently at the expense of less efficient acquisition of carbon. We suggest that selection for efficient utilization of the resource in lowest relative supply has been a strong driving force behind the physiological adaptation of both species to their environments.


Cognitive and Psychiatric Disturbances in Parkinsonian Syndromes.
Parkinsonian syndromes share clinical signs including akinesia/bradykinesia and rigidity, which are consequences of pathology involving dopaminergic substantia nigra neurons. Yet cognitive and psychiatric disturbances are common, even early in the course of disease. Executive dysfunction is often measurable in newly diagnosed Parkinson's disease. Treatment with dopaminergic medications, particularly dopamine agonists, has been associated with hallucinations and impulse control disorder. Older age, presence of APOE-4 gene, and/or other factors result in amyloid plaque deposition that, in turn, accelerates cortical Lewy body plus tau pathology, linking Dementia with Lewy Bodies and Parkinson's disease with early dementia with Alzheimer's disease. Treatments available for cognitive deficits, depression, and psychotic symptoms are discussed.


Predictors of success in a urology residency program.
In selecting a medical student for a urology residency, a set of preconceived criteria as to what will predict a successful resident are generally applied. To determine what factors predict an "excellent" clinical resident and a successful in-service test taker, we analyzed 10 years of urology resident files. PARTICIPANTS AND STUDY DESIGN: Retrospective chart review of 29 urology residents at Washington University graduating from July 2000 to July 2009. Medical student applications and interview evaluations were compared with future performance as a general surgical intern and then as a urology resident, in terms of clinical performance and in-service examination scores. Of 29 residents, based on clinical evaluations over 4 years of urology residency, 12 were "excellent," 17 "average and needing improvement." "Excellent" residents had higher applicant rank submitted to the "match" (7.2 vs. 12.1, p = 0.04) and better letters of recommendation (3.0 vs. 2.5, 0.018). "Excellent" residents also had better evaluations as an intern (3.9 vs 2.7, p < 0.001). "Good" urology in-service examination test takers compared with "below average" test takers noted higher rank on the match list (7.8 vs 12.1, p = 0.04), better quality med school (2.6 vs 2.0; p = 0.002), higher USMLE scores (92.5 vs 86.6% tile, p = 0.02), American Board of Surgery in-training examination (ABSITE) score (58.6 vs 37.2% tile, p = 0.04), and were more likely to pass the board examination (100% vs 76.9%, p = 0.03). Residents with higher clinical evaluations were also more likely to go into fellowships (83.3% vs 16.2%, OR = 23.3) and academic careers (41.6 vs 11.1%, OR = 5.71). Performance as a surgery intern predicts future performance as a GU Resident. "Good" test takers as medical students and as interns continue to test well as GU residents. Early identification, intervention, and mentoring while still an intern are essential. Selection criteria we currently use to select GU residents are surprisingly predictive.


Highly enantioselective copper(I)-catalyzed conjugate addition of 1,3-diynes to α,β-unsaturated trifluoromethyl ketones.
The conjugate diynylation of α,β-unsaturated trifluoromethyl ketones is carried out in the presence of a low catalytic load (2.5 mol%) of a copper(I)-MeOBIPHEP complex, triethylamine and a terminal 1,3-diyne. Pre-metalation of the terminal 1,3-diyne with stoichiometric or higher amounts of dialkylzinc reagent is not required. The corresponding internal diynes bearing a propargylic stereogenic center are obtained with good yields and excellent enantioselectivities.


Tuftsin and D-Arg3-tuftsin possess analgesic action.
Tuftsin has marked analgesic activity but is less potent than D-Arg3-tuftsin. The absence of an antagonistic effect of naloxone on tuftsin and its analogue suggests that these substances do not act on opiate receptors. Tuftsin and its analogues may represent a new class of substances of interest in the search for new analgesics.


Identification and function of circular RNA hsa_circ_0071106: A novel biomarker for differentiation degree of esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma (ESCC) has a high degree of malignancy, and there is currently no effective treatment. Circular RNA is a novel endogenous noncoding RNA with a stable loop structure. Several theories have been proposed regarding its biogenesis and usefulness as a biomarker in various cancers. Here we explore the predictive value and potential functions of a candidate circRNA (hsa_circ_0071106) in ESCC. The altered expression of hsa_circ_0071106 was validated in clinical tissue samples from 64 patients with ESCC. The correlation between the clinical characteristics of these patients and the expression of hsa_circ_0071106 was analyzed by the chi-square test. The receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to evaluate the diagnostic value of hsa_circ_0071106. The human esophageal carcinoma cell lines ECA109 and ECA9706 and the normal human esophageal epithelial cell line (HET-1A) were applied for functional analysis of hsa_circ_0071106. qRT-PCR, sanger sequencing, agarose gel electrophoresis, RNase R digestion assay, Actinomycin D inhibition assay, nucleoplasm separation assay, and FISH assays were utilized to verify the circular characteristics and subcellular localization of hsa_circ_0071106. SiRNA and circRNA interference lentivirus was constructed to inhibit the expression of hsa_circ_0071106 in the ECA109 and ECA9706 cell lines. We used the EdU assay, Transwell assay, and flow cytometry to detect changes in cell proliferation, invasion, migration, and apoptosis. We identified that hsa_circ_0071106 showed significantly decreased expression levels in ESCC cells (P < 0.001) and tissue samples (P < 0.001). The correlation analysis of clinicopathological features and gene expression revealed that low expression of hsa_circ_0071106 was related to poor differentiation grade (P < 0.05). ROC curves indicated that hsa_circ_0071106 might have a diagnostic value for ESCC (AUC = 0.826, 95% CI: 0.748-0.904) and a predictive value for a high degree of histological differentiation (AUC = 0.730, 95% CI: 0.607-0.854). Hsa_circ_0071106 has a stable circular structure and was primarily localized in the cytoplasm. A transient knockdown of hsa_circ_0071106 by siRNA promotes proliferation, migration, and invasion and inhibits apoptosis of ESCC cells. A steady knockdown of hsa_circ_0071106 by a lentivirus knockout vector significantly promoted cell migration and invasion in ECA109 and ECA9706 cell lines. Hsa_circ_0071106 was a downregulated circRNA related to ESCC and promoted ESCC progression by regulating cell migration and invasion. These findings suggest that hsa_circ_0071106 could be a promising diagnostic biomarker and potential therapeutic target and might predict ESCC's histological differentiation degree.


Timing of meiotic stages in oocytes of the Syrian hamster (Mesocricetus auratus) and analysis of induced chromosome aberrations.
The stages of maturation of oocytes (meiotic stages) in adult Syrian hamsters (Mesocricetus auratus) have been timed following superovulation treatment. Timing and superovulation were induced by an injection of pregnant mares' serum on the first morning of the estrus cycle, followed by injection of human chorionic gonadotropin (HCG) in the evening of the fourth day. The oocytes completed the prophase of the first maturation division 3 h after the injection of HCG. Ovulation began 9 1/2 h after the injection. A method of analysis of metaphase II chromosomes of Syrian hamster oocytes 16 h after injection of HCG is described. This method seems to be appropriate for the examination of the induction of genetic defects during oogenesis. Female hamsters were treated with 2,3,5-triethyleneimonobenzoquione-1,4. The induced chromosome aberrations were analysed. Dosis-dependent response could be demonstrated.


Eligibility of the movement-based classification systems in the diagnosis of patients with low back pain: A systematic review.
To evaluate the eligibility of the movement-based classification systems in the diagnosis of patients with low back pain. The present systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta -Analysis guidelines. Different databases including PubMed, Science Direct, OVID, MEDLINE, CINAHL, EMBASE, ProQuest and Google Scholar were searched from January 1990 to December 2017. All studies assessed the reliability and validity of the movement-based classification systems to diagnose patients with low back pain were included. The keywords used to search the studies were: "reliability", "validity", "classification", "movement impairment" and "low back pain". Study selection and data extraction were performed by two independent reviewers. Sixteen articles were met the inclusion criteria. Of these articles, 13 studies assessed the reliability and validity of movement-based classification systems to categorize patients with low back pain. Two out of 16 articles compared patients with low back pain and healthy subjects and one article had no control group. The results of the reviewed studies demonstrated that movement-based classification systems are valid and reliable enough to categorize patients with low back pain.


A secure remote health monitoring model for early disease diagnosis in cloud-based IoT environment.
Internet of Things (IoT) and smart medical devices have improved the healthcare systems by enabling remote monitoring and screening of the patients' health conditions anywhere and anytime. Due to an unexpected and huge increasing in number of patients during coronavirus (novel COVID-19) pandemic, it is considerably indispensable to monitor patients' health condition continuously before any serious disorder or infection occur. According to transferring the huge volume of produced sensitive health data of patients who do not want their private medical information to be revealed, dealing with security issues of IoT data as a major concern and a challenging problem has remained yet. Encountering this challenge, in this paper, a remote health monitoring model that applies a lightweight block encryption method for provisioning security for health and medical data in cloud-based IoT environment is presented. In this model, the patients' health statuses are determined via predicting critical situations through data mining methods for analyzing their biological data sensed by smart medical IoT devices in which a lightweight secure block encryption technique is used to ensure the patients' sensitive data become protected. Lightweight block encryption methods have a crucial effective influence on this sort of systems due to the restricted resources in IoT platforms. Experimental outcomes show that K-star classification method achieves the best results among RF, MLP, SVM, and J48 classifiers, with accuracy of 95%, precision of 94.5%, recall of 93.5%, and f-score of 93.99%. Therefore, regarding the attained outcomes, the suggested model is successful in achieving an effective remote health monitoring model assisted by secure IoT data in cloud-based IoT platforms.


Wild-type precore and core promoter sequences in patients with acute self-limited or chronic hepatitis B.
Mutations in the precore region and core promoter were compared between patients with acute and chronic hepatitis B. There were 69 patients with acute self-limited hepatitis B and 210 with chronic hepatitis B who had been followed for > 15 years. The hepatitis B virus (HBV) of genotypes A, B and C was detected in 14 (23%), 8 (13%) and 28 (45%) of the patients with acute self-limited hepatitis, respectively, in contrast to 11 (5%), 25 (12%) and 167 (80%) of those with chronic hepatitis. At presentation, hepatitis B e antigen (HBeAg) in serum was the more common (82% versus 65%, P < 0.05), and the wild-type sequences of the precore region (100% versus 74%, P < 0.001) and core promoter (88% versus 36%, P < 0.00001) were more frequent in the 50 patients with acute self-limited hepatitis than the 203 patients with chronic hepatitis B who were infected with HBV of genotype A, B or C. Wild-types of both the precore region and core promoter persisted in acute self-limited hepatitis, while they decreased from 28% to 10% in chronic hepatitis over the course of > 15 years. HBV with the wild-type sequences of the precore region and core promoter prevails in patients with acute self-limited hepatitis, unlike in patients with chronic hepatitis.


Food intake suppression by growth factors and platelet peptides by direct action in the central nervous system.
Intracerebroventricular (i.c.v.) microinfusion of epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) and platelet factor 4 (PF4) suppressed 2 h and nighttime food intake in rats. The following daytime food intake did not change or increased. I.c.v. infusion of platelet-derived growth factor (PDGF) suppressed only 2 h food intake. I.c.v. infusion of bovine serum albumin (BSA), nerve growth factor (NGF), or inactivated EGF, bFGF and PF4 had no effect. Intraperitoneal (i.p.) administration of EGF, bFGF, PF4 and PDGF in doses equivalent to or higher than those administered centrally had no effect. The results suggest a central action of growth factors and platelet peptides on feeding regulation.


Novel genetic structure associated with an extended-spectrum beta-lactamase blaVEB gene in a Providencia stuartii clinical isolate from Algeria.
A ceftazidime-resistant Providencia stuartii isolate from Algeria harbored a ca. 160-kb conjugative plasmid that contained a truncated bla(VEB-1b) gene flanked by three 135-bp repeated elements. This work gives further evidence of the worldwide spread of bla(VEB) genes that are associated with genetic structures other than class 1 integrons.


Incidence of surgical rib fixation at chest wall injury society collaborative centers and a guide for expected number of cases (CWIS-CC1).
Surgical stabilization of rib fractures (SSRF) improves outcomes in certain patient populations. The Chest Wall Injury Society (CWIS) began a new initiative to recognize centers who epitomize their mission as CWIS Collaborative Centers (CWIS-CC). We sought to describe incidence and epidemiology of SSRF at our institutions. A retrospective registry evaluation of all patients (age > 15 years) treated at international trauma centers from 1/1/20 to 7/30/2021 was performed. Variables included: age, gender, mechanism of injury, injury severity score, abbreviated injury severity score (AIS), emergency department disposition, length of stay, presence of rib/sternal fractures, and surgical stabilization of rib/sternal fractures. Classification and regression tree analysis (CART) was used for analysis. Data were collected from 9 centers, 26,084 patient encounters. Rib fractures were present in 24% (n = 6294). Overall, 2% of all patients underwent SSRF and 8% of patients with rib fractures underwent SSRF. CART analysis of SSRF by AIS-Chest demonstrated a difference in management by age group. AIS-Chest 3 had an SSRF rate of 3.7, 7.3, and 12.9% based on the age ranges (16-19; 80-110), (20-49; 70-79), and (50-69), respectively (p = 0.003). AIS-Chest > 3 demonstrated an SSRF rate of 9.6, 23.3, and 39.3% for age ranges (16-39; 90-99), (40-49; 80-89), and (50-79), respectively (p = 0.001). Anticipated rate of SSRF can be calculated based on number of rib fractures, AIS-Chest, and age. The disproportionate rate of SSRF in patients age 50-69 with AIS-Chest 3 and age 50-79 with AIS-Chest > 3 should be further investigated, as lower frequency of SSRF in the other age ranges may lead to care inequalities.


PFAS accumulation in several terrestrial plant and invertebrate species reveals species-specific differences.
Despite the known persistence and bioaccumulation potential of perfluoroalkyl substances (PFAS), much uncertainty exists regarding their bioavailability in the terrestrial environment. Therefore, this study investigated the influence of soil characteristics and PFAS concentrations on the adsorption of PFAS to soil and their influence on the PFAS bioavailability to terrestrial plants and invertebrates. PFAS concentrations and profile were compared among different invertebrate and plant species and differences between leaves and fruits/nuts of the plant species were assessed. Soil concentrations were primarily affected by organic carbon content. The PFAS accumulation in biota was, except for PFOA concentrations in nettles, unrelated to the soil concentrations, as well as to the soil characteristics. The PFAS profiles in soil and invertebrates were mainly dominated by PFOA and PFOS, whereas short-chained PFAS were more abundant in plant tissues. Our results show that different invertebrate taxa accumulate different PFAS, likely due to dietary differences. Both long-chained and, to lesser extent, short-chained PFAS were observed in herbivorous invertebrate taxa, whereas the carnivorous invertebrates only accumulated long-chained PFAS. Correlations were observed between PFOA concentrations in herbivorous invertebrates and in the leaves of some plant species, whereas such relationships were absent for the carnivorous spiders. It is essential to continuously monitor PFAS exposure in terrestrial organisms, taking into account differences in bioaccumulation, and subsequent potential toxicity, among taxa, in order to protect the terrestrial ecosystem.


Tissue-engineered vascular grafts and regeneration mechanisms.
Cardiovascular diseases (CVDs) are life-threatening diseases with high morbidity and mortality worldwide. Vascular bypass surgery is still the ultimate strategy for CVD treatment. Autografts are the gold standard for graft transplantation, but insufficient sources limit their widespread application. Therefore, alternative tissue engineered vascular grafts (TEVGs) are urgently needed. In this review, we summarize the major strategies for the preparation of vascular grafts, as well as the factors affecting their patency and tissue regeneration. Finally, the underlying mechanisms of vascular regeneration that are mediated by host cells are discussed.


[Primary strength of conventional and alternative suture techniques of the rotator cuff. A biomechanical study].
The aim of this biomechanical study was to evaluate rotator cuff repair strength using different suture anchor techniques compared to conventional repair, taking into consideration the native strength of the supraspinatus tendon. Therefore, a defined defect of the supraspinatus was created in 50 freshly frozen cadaver specimen (group size n = 10; median age at death: 56 years). Five methods were employed for cuff repair: standard transosseous suture, modified transosseous suture with patch augmentation and three suture anchors (Acufex Wedge TAG, Acufex Rod TAG und Mitek GII). The maximum tensile load of the five techniques was: standard transosseous suture, 410 N; modified transosseous suture, 552 N; Wedge TAG, 207 N; Rod TAG, 217 N; Mitek GII, 186 N. The difference between the suture anchor and standard techniques were highly significant (P < 0.001). In this series, the Mitek Gll anchor showed the lowest anchor dislocation rate at 3% (n = 1). The Wedge TAG system had a dislocation rate of 27% (n = 8) and the Rod TAG system 43% (n = 13). Suture anchor techniques revealed about 20%, the standard technique 34% and its modification 60% of the hypothetically calculated native tendon strength. Compared to conventional transosseous suture techniques, the use of the suture anchors tested in this series does not significantly increase the primary fixation strength of rotator cuff repair. The metallic implant with two barbs (Mitek GII) seems to be superior to the polyacetal anchors when inserted into the spongiform bone of the greater tubercle. The considerably weaker repair strength needs to be taken into consideration in postoperative patient rehabilitation, especially after the use of suture anchors.


The impact of routine open nonsuction drainage on fluid accumulation after thyroid surgery: a prospective randomised clinical trial.
Thyroid drains following thyroid surgery are routinely used despite minimal supportive evidence. Our aim in this study is to determine the impact of routine open drainage of the thyroid bed postoperatively on ultrasound-determined fluid accumulation at 24 hours. We conducted a prospective randomised clinical trial on patients undergoing thyroid surgery. Patients were randomly assigned to a drain group (n = 49) or a no-drain group (n = 44) immediately prior to wound closure. Patients underwent a neck ultrasound on day 1 and day 2 postoperatively. After surgery, we evaluated visual analogue scale pain scores, postoperative analgesic requirements, self-reported scar satisfaction at 6 weeks and complications. There was significantly less mean fluid accumulated in the drain group on both day 1, 16.4 versus 25.1 ml (P-value = 0.005), and day 2, 18.4 versus 25.7 ml (P-value = 0.026), following surgery. We found no significant differences between the groups with regard to length of stay, scar satisfaction, visual analogue scale pain score and analgesic requirements. There were four versus one wound infections in the drain versus no-drain groups. This finding was not statistically significant (P = 0.154). No life-threatening bleeds occurred in either group. Fluid accumulation after thyroid surgery was significantly lessened by drainage. However, this study did not show any clinical benefit associated with this finding in the nonemergent setting. Drains themselves showed a trend indicating that they may augment infection rates. The results of this study suggest that the frequency of acute life-threatening bleeds remains extremely low following abandoning drains. We advocate abandoning routine use of thyroid drains. ISRCTN94715414.


Health System-Academic Partnerships: Essential to Increasing the APRN Workforce.
This month's column highlights the importance of established health system academic partnerships in strengthening the advanced practice RN workforce.


Identification of Apiaceae using ITS, ITS2 and psba-trnH barcodes.
Apiaceae plants are used as medicinal herbs, pesticides, spices, and vegetables; thus, accurately identifying Apiaceae species is important. The grassland ecosystem of Heilongjiang Province in northern China has huge reserves of wild Apiaceae plants, but few reports have systematically documented their diversity. In this study, 275 Apiaceae plants of 23 species in 18 genera were collected from this area. We identified Apiaceae species by using nuclear internal transcribed spacer (ITS/ITS2) and psbA-trnH (chloroplast non-coding region) sequences based on experimental data. The identification efficiency of ITS, ITS2 and psbA-trnH sequences was determined and evaluated by sequence alignment and analysis, intraspecific and interspecific genetic distance analyses, and phylogenetic tree construction. ITS, ITS2 could distinguish 21 species from 17 genera of Apiaceae with good identification effect. When identifying species in the Apiaceae family, ITS2 can be used as the core barcode and psbA-trnH can be used as the supplementary barcode. These results can enrich the reference Apiaceae DNA barcode database.


Granulosa cells as a source and target organ for tumor necrosis factor-alpha.
Tumor necrosis factor (TNF-alpha), a 17 kDa cytokine, is a product of activated macrophages which was recently shown to be produced by rat and bovine granulosa cells. In the present work, human granulosa cells derived from preovulatory follicles were used. It was demonstrated that human granulosa cells produce TNF-alpha (5-10 units/300,000 cells per 15 h). This production was increased by addition of follicle-stimulating hormone or by a combination of human chorionic gonadotrophin and CSF to the culture media. TNF was also found in bovine follicular fluid and the concentration was higher in the periovulatory than mid-cycle follicles. TNF-alpha was found to increase prostaglandin F-2 alpha production by human granulosa cells (P less than 0.001). We conclude that granulosa cells are both a source and target organ for TNF-alpha.


Use of Affinity Purification-Mass Spectrometry to Identify Phosphorylated Tau Interactors in Alzheimer's Disease.
Phosphorylated tau is the main protein present in neurofibrillary tangles, the presence of which is a key neuropathological hallmark of Alzheimer's disease (AD). The toxic effects of phosphorylated tau are likely mediated by interacting proteins; however, methods to identify these interacting proteins comprehensively in human brain tissue are limited. Here, we describe a method that enables the efficient identification of hundreds of proteins that interact with phosphorylated tau (pTau), using affinity purification-mass spectrometry (AP-MS) on human, fresh-frozen brain tissue from donors with AD. Tissue is homogenized using a gentle technique that preserves protein-protein interactions, and co-immunoprecipitation of pTau and its interacting proteins is performed using the PHF1 antibody. The resulting protein interactors are then identified using label-free quantitative liquid chromatography-mass spectrometry (LC-MS)/MS. The Significance Analysis of INTeractome (SAINT) algorithm is used to determine which proteins significantly interact with pTau. This approach enables the detection of an abundance of all 6 isoforms of tau, 23 phosphorylated residues on tau, and 125 significant pTau protein interactors, in human AD brain tissue.


Zinc deficiency as an independent prognostic factor for patients with early hepatocellular carcinoma due to hepatitis virus.
Although a reduced serum zinc level is often observed in patients with chronic liver disease due to hepatitis virus, its prognostic importance has not been adequately investigated. This study aimed to elucidate the association of zinc deficiency with prognosis, especially in early hepatocellular carcinoma (HCC) patients. From 2005 to 2018, 466 patients with naïve HCC due to hepatitis virus were enrolled (327 men, 139 women; median age 70 years; hepatitis C virus [HCV] n = 389, hepatitis B virus [HBV] n = 69, hepatitis C virus and hepatitis B virus n = 8; Child-Pugh A n = 367, Child-Pugh B n = 82; Child-Pugh C n = 17; TNM-LCSGJ stage I n = 150, stage II n = 181, stage III n = 91, stage IVa n = 26, state IVb n = 18). Of the 466 patients, 287 were within the Milan criteria (early HCC) and treated curatively. Zinc deficiency was defined as <60 μg/dL. Clinical records and prognostic factors were retrospectively evaluated. The levels of serum zinc became lower with chronic liver disease progression (Child-Pugh A, B, C: 64.3 ± 14.3, 52.3 ± 15.7, 48.4 ± 13.5 μg/dL, respectively; P < 0.001). In early HCC patients treated curatively, overall survival and recurrence rates were better in patients treated curatively and without zinc deficiency as compared with patients with zinc deficiency (3-year overall survival 86.5% vs. 77.2%, 5-year overall survival 73.5% vs. 43.8%, P < 0.001; 3-year recurrence 44.8% vs. 58.3%, 5-year recurrence 56.8% vs. 77.5%, P = 0.002). Not only infection control of hepatitis virus (sustained virological response in HCV or nucleos(t)ide analogs in HBV; HR 0.078, P < 0.001), but also zinc deficiency (HR 1.773, P = 0.041) were significant prognostic factors for death. Serum levels of zinc were reduced in association with chronic liver disease grade progression. In addition to infection control of hepatitis virus, zinc deficiency might be a significant prognostic factor for survival in patients with early HCC due to viral hepatitis treated curatively.


Poly(ADP-ribose) polymerase-1 is involved in the neuronal death induced by quinolinic acid in rats.
Reactive oxygen and nitrogen species formation leads to DNA damage in animals treated with quinolinic acid. Poly(ADP-ribose) polymerase-1 (PARP-1) is a protein involved in the DNA base excision repair system. Its overactivation promotes cellular energy deficit and necrosis. Here, we evaluated the effect of PJ-34, a potent inhibitor of PARP-1, on the neuronal damage induced by quinolinic acid. Animals were administered with PJ-34 (10 mg/kg, i.p.), 1 h before and 1 h after a striatal infusion of 1 microl of quinolinic acid (240 nmol). PJ-34 clearly attenuated the circling behavior produced by quinolinic acid and completely prevented the histological damage induced by the toxin. The protective effect of PJ-34 suggests that PARP-1 activation is playing an active role in the neuronal death induced by quinolinic acid.