Mechanism of liver-specific metastatic tumor spread in a murine tumor model.
Malignant tumors frequently show an organ-specific metastatic spread, the causes of which are still largely unknown. Using an experimental tumor model, a methylcholanthrene-induced pleomorphic myofibrosarcoma ER 15-P of the C57Bl6J mouse, we wanted to find out whether this phenomenon is due to an adaptation or to a selection of tumor cells. After i.v. injection of tumor cells from the primary ER 15-P into the tail vein of male mice, metastases were regularly found in the lungs, mediastinal lymph nodes, and brain, as well as in the liver and kidneys, and occasionally in the adrenals. The following experimental procedures were used to isolate a tumor cell line with a possible liver preference: (1) Tumor cells from the primary ER 15-P were injected into a mesenteric vein of male mice. Tumor cells from the resulting liver colonies were again injected into the portal system of one group of mice. In a second group, part of the same cell suspension was injected into the tail vein. This procedure was performed four times. (2) Tumor cells from the primary ER 15-P were applied into the tail vein of male mice. Tumor cells from the resulting liver metastases were reinjected directly into the tail vein. This experiment was repeated three times. (3) Tumor cells from the primary ER 15-P were injected into the tail vein of male mice. Tumor cells from liver metastases were then injected, first, into the portal system of one group of male mice, and thereafter into the tail vein of another group of animals. This experiment was repeated twice. The following results were obtained: (1) By a repeated adaptation of tumor cells from the primary ER 15-P to liver tissue, no tumor cell line could be isolated that would show a preferential metastatic spread to this organ after tail-vein injection. (2) Repeated i.v. passages of tumor cells from liver metastases into the tail vein led to the selection of a tumor cell line with a tendency to liver metastasis. (3) Tumor cells selected from liver metastases induced via tail-vein injection showed, after a prolonged stay in the liver and a successive i.v. passage into the tail vein, a marked specificity for this organ. These results indicate that the liver-specific spread of tumor cells in our model is based on the selection of a tumor cell line from the primary ER 15-P influenced by the hepatic microenvironment.


Phenanthrene: establishing lower and upper bounds to the binding energy of a very weakly bound anion.
Quite a few molecules do not form stable anions that survive the time needed for their detection; their electron affinities (EA) are either very small or negative. How does one measure the EA if the anion cannot be observed? Or, at least, can one establish lower and upper bounds to their EA? We propose two approaches that provide lower and upper bounds. We choose the phenanthrene (Ph) molecule whose EA is controversial. Through competition between helium evaporation and electron detachment in HenPh- clusters, formed in helium nanodroplets, we estimate the lower bound of the vertical detachment energy (VDE) of Ph- as about -3 meV. In the second step, Ph is complexed with calcium whose electron affinity is just 24.55 meV. When CaPh- ions are collided with a thermal gas of argon, one observes Ca- product ions but no Ph-, suggesting that the EA of Ph is below that of Ca.


N,N-Bis(9-methyl-3-carbazolyl)-4-anisidine as an Electroactive Material for Use in Perovskite Solar Cells.
Di(9-methyl-3-carbazolyl)-(4-anisyl)amine is presented as an effective hole-transporting material suitable for application in perovskite solar cells. It is obtained by a three-step synthesis from inexpensive starting compounds. It has a relatively high glass transition temperature of 93 °C and thermal stability with 5% weight loss at 374 °C. The compound exhibits reversible double-wave electrochemical oxidation below +1.5 V and polymerization at higher potential. A mechanism for its oxidation is proposed based on electrochemical impedance and electron spin resonance spectroscopy investigations, ultraviolet-visible-near-infrared absorption spectroelectrochemistry results, and density functional theory-based calculations. Vacuum-deposited films of the compound are characterized by a low ionization potential of 5.02 ± 0.06 eV and hole mobility of 10-3 cm2/(Vs) at an electric field of 4 × 105 V/cm. The newly synthesized compound has been used to fabricate dopant-free hole-transporting layers in perovskite solar cells. A power conversion efficiency of 15.5% was achieved in a preliminary study.


Extensive scalds following accidental immersion in hot water pools.
The scalds produced by immersion in hot water pools were extensive, usually of superficial depth on the upper parts of the body and deep dermal or full thickness skin loss on the lower parts. Blisters appeared rather slowly, within 2 days post-burn and often dispersed spontaneously. The estimated burned area on admission may thus be smaller than found subsequently. This study showed that the volume of fluid required for adequate resuscitation during the first post-burn day may be only 1.5 ml/kg/% BSA burned. Deep dermal burns were treated preferably by early tangential excision and grafting. The full thickness skin loss was treated by escharectomy and skin grafts.


The use of N-acetylcysteine for the prevention of hypertension in the reduced uterine perfusion pressure model for preeclampsia in Sprague-Dawley rats.
To determine whether N-acetylcysteine attenuates abnormal changes in the reduced uterine perfusion pressure model. Twenty-four timed-pregnant Sprague-Dawley rats underwent sham surgery or the reduced uterine perfusion pressure procedure on day 15 of 22. Reduced uterine perfusion pressure animals were treated with N-acetylcysteine (100 mg/kg) or saline twice daily until delivery. On day 21 of 22, mean arterial pressure was determined and maternal tissue was collected and stored. Pups and pup brains were weighed. Statistical analysis was performed using 1-way analysis of variance and the Tukey-Kramer test with significance at P < .05. There was a significant increase in blood pressure with the reduced uterine perfusion pressure procedure (P = .016), which was alleviated by N-acetylcysteine (P = .044). There was a significant decrease in pup weight and brain weight with the reduced uterine perfusion pressure procedure (P = .043 and P = .046, respectively). N-acetylcysteine restored pup brain weight (P = .021) but had no significant effect on pup weight. N-acetylcysteine reduced blood pressure without adversely effecting fetal weight.


Biotransformation of adsorbed arsenic on iron minerals by coexisting arsenate-reducing and arsenite-oxidizing bacteria.
Bacteria with arsenate-reducing (ars) and arsenite-oxidizing (aio) genes usually co-exist in aerobic environments, but their contrast impacts on arsenic (As) speciation and mobility remain unclear. To identify which kind of bacteria dominate As speciation under oxic conditions, we studied the biotransformation of adsorbed As on goethite in the co-existence of Pantoea sp. IMH with ars gene and Achromobacter sp. SY8 with aio gene. The incubation results show that SY8 dominated the dissolved As speciation as As(V), even though aio exhibited nearly 5 folds lower transcription levels than ars in IMH. Nevertheless, our XANES results suggest that SY8 showed a negligible effect on solid-bound As speciation whereas IMH reduced adsorbed As(V) to As(III). The change in As speciation on goethite surfaces led to a partial As structural change from bidentate corner-sharing to monodentate corner-sharing as evidenced by our EXFAS analysis. Our Mössbauer spectroscopic results suggest that the incubation with SY8 reduced the degree of crystallinity of goethite, and the reduced crystallinity can be partly compensated by IMH. The changes in As adsorption structure and in goethite crystallinity had a negligible effect on As release. The insights gained from this study improve our understanding of biotransformation of As in aerobic environment.


Evidence for stereospecificity of the P1-purinoceptor.
1 The effects of adenosine, 5'-N-ethylcarboxamidoadenosine (NECA), 2-chloroadenosine, 2-azidoadenosine, and their L-enantiomers were examined on driven left atria, trachea and transmurally stimulated ileum of the guinea-pig. 2 In each tissue the order of potency of the D-enantiomers for producing inhibitory effects was NECA greater than 2-chloroadenosine greater than 2-azidoadenosine greater than adenosine. 3 The log concentration-response curve of each agonist was shifted to the right in the presence of the P1-purinoceptor antagonist, theophylline. 4 Dipyridamole, which blocks adenosine uptake, potentiated the effects of adenosine but not those of the D-enantiomers of adenosine analogues. 5 The greater potency of the adenosine analogues therefore, is at least partly due to their resistance to tissue uptake and subsequent enzymatic destruction. 6 The L-enantiomers of adenosine and its analogues did not produce inhibitory responses in the driven left atria or transmurally stimulated ileum. At high concentrations relaxations of the tracheal muscle were obtained, with the potency series L-NECA greater than 2-chloro-L-adenosine greater than 2-azido-L-adenosine greater than L-adenosine. 7 It is concluded that the postsynaptic P1-purinoceptors in the guinea-pig atria and trachea and the presynaptic P1-purinoceptors on cholinergic nerve terminals in guinea-pig ileum are stereospecific for the D-enantiomers of adenosine and its analogues.


A brief cognitive behavioural intervention is cost-effective for primary care patients with medically unexplained physical symptoms compared to usual care.
To assess the cost-effectiveness of a brief cognitive behavioural intervention for patients with medically unexplained physical symptoms (MUPS) provided by a mental health nurse practitioner (MHNP) in primary care in comparison with usual care. We performed an economic evaluation from a societal perspective alongside a cluster randomised controlled trial with 12 months follow-up. The primary outcome was quality-adjusted life-years (QALYs). Secondary outcomes were the RAND-36 physical component summary score (PCS), somatic symptom severity (Patient Health Questionnaire (PHQ-15), and anxiety and depression symptoms (Hospital Anxiety and Depression Scale (HADS)). Missing data were imputed using multiple imputation. We used non-parametric bootstrapping to estimate statistical uncertainty. The bootstrapped cost-effect pairs were used to estimate cost-effectiveness planes and cost-effectiveness acceptability curves. Mean total costs in the intervention group were significantly lower than in the usual care group (mean difference - 2300€, 95% CI -3257 to -134). The mean difference in QALYs was 0.01 (95% CI -0.01 to 0.04), in PCS 2.46 (95% CI 1.44 to 3.47), in PHQ-15 -0.26 (95% CI -0.81 to 0.28), and in HADS -0.07 (-0.81 to 0.67). At a willingness to pay of 0 € per additional unit of effect, the probability of the intervention being cost-effective was 0.93 for QALYs and 0.92 for PCS, PHQ-15 and HADS scores. Our intervention is cost-effective compared to usual care for patients with MUPS. Implementation of the intervention has the potential to result in a significant decline in costs. However, large scale implementation would require increased deployment of MHNPs.


Novel mitochondrial tRNALeu(UUR) 3261A > g mutation in two pedigrees with essential hypertension.
Essential hypertension (EH) was associated with mitochondrial tRNA mutations. This study was designed to assess the association between EH and mitochondrial dysfunction. A total of 30 individuals from two different Chinese families exhibit maternally inherited EH were assessed for genetic, clinical, and biochemical phenotypes pertaining to EH and mitochondrial functionality. These analyses included assessments of tRNALeu(UUR) 3261A > G mutation status, mitochondrial membrane permeability, mitochondria-associated ATP and reactive oxygen species (ROS) generation, and electron transport chain functionality. EH was detected in 6 total analyzed members of the two families assessed in the present study, with its initial age of onset and presentation varying among patients. These patients with EH exhibited the tRNALeu(UUR) 3261A > G mutation and were of the B5 and D4 Eastern Asian mitochondrial haplogroups. This 3261A > G mutation was predicted to result in disruption of normal tRNALeu(UUR) activity owing to the destabilization of conserved base pairing (30A-40U). Consistent with this prediction, we found that cybrid cell lines exhibiting this 3261A > G mutation exhibited a ~49.05% decrease in baseline tRNALeu(UUR) levels. These cells additionally exhibited ~44.81% reductions in rates of mitochondrial translation. To facilitate future molecular diagnosis, the 3261A > G mutation should be included in the list of hereditary risk factors. Our findings will aid in the counseling of EH families.


Sequential cyclophosphamide-prednisone and vincristine-bleomycin (CPOB). An effective, schedule-dependent treatment for advanced diffuse histiocytic lymphoma.
In an Eastern Cooperative Oncology Group non-Hodgkin's lymphoma clinical trial, 90 patients with Stage III or IV diffuse histiocytic lymphoma (DHL) were treated with one of four chemotherapy regimens. All patients were previously untreated with chemotherapy, and careful restaging was required to document responses. Each treatment included cyclophosphamide, vincristine and prednisone (COP) plus Adriamycin (COPA), BCNU (BCVP) or bleomycin (COPB and CPOB). The two bleomycin-containing regimens differed only in the schedule of drug administration. CPOB-treated patients received cyclophosphamide on day 1, prednisone on days 1 to 5 and vincristine and bleomycin on day 15 of each 21-day cycle. COPB-treated patients received the same four drugs in the same dosage; however, the schedule was changed so that vincristine and bleomycin were given on day 1. Treatment of responders was continued for 8 cycles. Those with a complete response (CR) were randomized to maintenance therapy with BCVP or no treatment. Treatment with CPOB yielded a CR rate of 55% compared to 25% for COPB (P = 0.07). In contrast to COPB, treatment with CPOB was associated with a significantly longer median duration of CR (26.5 versus 5.7 months; P less than 0.05) and median survival (27.7 versus 11.2 months; P less than 0.02). The CR rate was 31% for BCVP and 45% for COPA, and the median survivals were 10.7 months and 14.4 months, respectively. One half of the CPOB-treated patients who achieved CR remained alive in continuous CR after 30 to 72 months. No advantage for maintenance therapy was observed. Myelotoxicity was greater with CPOB than COPB, but comparable to COPA. This trial demonstrated that the results of treatment of DHL with COP plus bleomycin were strikingly dependent upon the schedule of administration of bleomycin and vincristine. Bleomycin effectively combined with COP, as in CPOB, yielded results comparable to those obtained when Adriamycin was added to COP. CPOB appears to be an effective treatment for DHL that should be considered as an alternative to other regimens, particularly for patients who cannot receive Adriamycin.


[Anesthesia selection in hypophysectomy by endoscopic transnasal sphenoidal approach].
To explore the anesthesia selection in resection of pituitary neoplasms by endoscopic transnasal sphenoidal approach. Fifty-six cases with pituitary tumor underwent transnasal sphenoidal endoscopic surgery . Among the 56 cases, 8 cases accepted general anesthesia and 48 cases accepted local anesthesia and sedation. All patients had no complains of surgery. 48 cases who accepted local anesthesia and sedation were completed surgery successfully, without graining and struggling during the operation. Local anesthesia and sedation is a simple, safe and good selection for resection of pituitary neoplasms by endoscopic transnasal sphenoidal approach.


[Expression of IL-6 and it's mRNA transcription in the process of rat periodontium remodeling influenced by various bite forces].
To study the expression of IL-6 in periodontal ligament fibroblasts (PLF) and osteoblasts in order to explain the molecular mechanism of the bite forte on periodontium remodeling. A rat model of different bite forces was established to study the expression of IL-6 and IL-6 mRNA in the PLF and osteoblasts with immunohistochemical (IHC) and in situ hybridization (ISH) techniques. In the group of disuse bite force, the expression of IL-6 and IL-6 mRNA in the PLF and osteoblasts enhanced apparently compared with that in the group of normal bite force. The gray level values enhanced respectively from 6.5886 +/- 1.6 to 38.8381 +/- 9.5 and from 11.8337 +/- 2.8 to 57.2623 +/- 13.6. The loosely arrangement of periodontal fibers and the resorption of alveolar bone were observed in histological study. In the group of compensation bite force, the same result was observed with IHC and ISH, the gray level values enhanced respectively from 6.3119 +/- 1.5 to 45.5456 +/- 11.1 and from 11.7714 +/- 2.8 to 81.9391 +/- 19.5, but the increase of periodontal fibers, the resorption and formation of alveolar bone were observed simultaneity in histological study. With the change of bite force, the expression of IL-6 and IL-6 mRNA in PLF and osteoblasts presents a certain regulation. IL-6 may play important roles in the effect of bite force on periodontium remodeling.


Insulin action and insulin secretion in identical twins with MODY. Evidence for defects in both insulin action and secretion.
To evaluate the pathogenetic mechanisms responsible for development of diabetes in the genetically inherited disease maturity-onset diabetes of the young (MODY), we have investigated a pair of identical twins (19 yr old) from a MODY family. One twin had nondiabetic fasting plasma glucose values but impaired glucose tolerance (IGT), whereas the other suffered from frank diabetes (fasting plasma glucose 12.5 mM). Differences in insulin secretion pattern and/or insulin action between the twins is supposed to be responsible for development of hyperglycemia in MODY. On the other hand, identical defects in insulin secretion and action in the twins may point to the primary genetic defect in MODY. Therefore, our aim was to investigate insulin secretion and insulin action in the twins to find these differences and similarities. We found that fasting plasma insulin and C-peptide values were slightly increased in the twins, whereas the responses of insulin and C-peptide to oral glucose tolerance tests (OGTT) and meals were similar in the twins and within normal range. The insulin responses to OGTT were, however, lower than expected from the glucose values, indicating a beta-cell defect. Despite elevated plasma insulin levels, basal hepatic glucose output (HGO) was normal in the IGT twin but increased by 75% in the diabetic twin. The maximally inhibitory effect of insulin on HGO, when estimated at euglycemia, was normal in the IGT twin but reduced by 60% in the diabetic twin. Furthermore, the maximal insulin-mediated glucose uptake in peripheral tissues was reduced by 40% in the diabetic twin.(ABSTRACT TRUNCATED AT 250 WORDS)


Retracted: DNMT1-Mediated DNA Methylation Targets CDKN2B to Promote the Repair of Retinal Ganglion Cells in Streptozotocin-Induced Mongolian Gerbils during Diabetic Retinopathy.
[This retracts the article DOI: 10.1155/2022/9212116.].


Interaction of SIGNR1 expressed by marginal zone macrophages with marginal zone B cells is essential to early IgM responses against Streptococcus pneumoniae.
The spleen plays a pivotal role in the immune defense against encapsulated bacteria such as Streptococcus pneumoniae. Murine splenic marginal zone macrophages express the C-type lectin SIGNR1, which is crucial for the capture of S. pneumoniae from blood. In this study, we demonstrate that SIGNR1 is able to interact in vitro with the juxtaposing marginal zone B cell population, which is responsible for the production of the early IgM response against the S. pneumoniae-epitope phosphorylcholine. Strikingly, SIGNR1-deficient mice display a reduction in the marginal zone B cell population. In addition, ex vivo B cell stimulation assays demonstrate a decrease in phosphorylcholine specificity in the splenic B cell population derived from SIGNR1-deficient mice, whereas the total IgM response is unaffected. Therefore, we hypothesize that antigens are presented by SIGNR1 expressed by marginal zone macrophages to the developing marginal zone B cell population thereby influencing the repertoire of this B cell population, which is pivotal for the early immune response against encapsulated bacteria such as S. pneumoniae.


A second generation global analysis program for the recovery of complex inhomogeneous fluorescence decay kinetics.
A fluorescence spectroscopy global data analysis environment is described. Within this analysis environment, multidimensional fluorescence decay data (time and frequency domains) can be analyzed in terms of a wide variety of photophysical models. A generalized compartmental analysis structure is utilized, where one can specify the functions used to link the various compartments together. All fitting parameters may be characterized by either discrete or distributed values. Applications of these new analysis programs to the examination of phase transitions in lipid/membrane systems are described.


Anatomical study of the sternoclavicular joint using high-frequency ultrasound.
The purpose of the present study was to determine whether ultrasound enables assessment of sternoclavicular structures. A preliminary study in 3 cadavers was followed by an ultrasound study, performed by 2 musculoskeletal radiologists working in consensus, in 59 patients without history of trauma, surgery or pain in the sternoclavicular joint. The visibility, echogenicity and thickness of the sternoclavicular structures were assessed. The anterior sternoclavicular ligament and the interclavicular ligament could be seen in all patients (mean thickness: 1.4 mm and 1.3 mm, respectively). The articular disc was clearly seen in 66.1% of cases, and shoulder antepulsion enabled analysis in an additional 20.3%. Intra-articular joint gas was frequent (33.89% of cases), preventing analysis of the disc in 2 patients. Only the superficial anterior aspect of the clavicular and sternal articular cartilages could be assessed. Joint effusion was seen in 6.8% of cases. Clavicular osteophytes, sternal osteophytes and bone irregularities at the anterior sternoclavicular ligament insertion were detected in 33.9%, 16.9% and 16.9% of cases, respectively. The anterior sternoclavicular ligament, interclavicular ligament and anterior intra-articular structures can be visualized by ultrasound. This means of assessment may have clinical applications, particularly in patients with trauma or microtrauma.


Synergistic enhancement of the antiproliferative activity of cis-diamminedichloroplatinum(II) by the ether lipid analogue BM41440, an inhibitor of protein kinase C.
The new phospholipid analogue 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine inhibits the phospholipid-calcium-dependent protein kinase, partially purified from Walker carcinoma cells with a Ki value of 0.56 microM. The compound inhibits the phorbol ester stimulated phosphorylation of the ribosomal protein S6 indicating that the depression of Ca2+-phospholipid-dependent protein kinase by the alkyl phospholipid also occurs in intact cells. The dose effect curve for the inhibition of cell proliferation by 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine in Walker cells exhibits a close correlation to the dose effect curve for the depression of Ca2+-phospholipid-dependent protein kinase activity. Although alternative mechanisms cannot be excluded, the data suggest that the growth inhibitory activity of 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine correlates with the inhibition of Ca2+-phospholipid-dependent protein kinase. The antiproliferative activity of 3-hexadecylmercapto-2-methoxy-methyl-propyl-1-phosphocholine is synergistically enhanced by cis-diamminedichloroplatinum(II).


Maximum voluntary bite force in patients with alloplastic total TMJ replacement--a prospective study.
Alloplastic temporomandibular total joint replacement (TJR) for end-stage disease, congenital disorders and following ablative oncological surgery has been shown to reduce pain and improve function. The purpose was to assess the maximum voluntary bite force and maximum interincisal opening (MIO) in patients undergoing alloplastic total temporomandibular joint replacement (TJR). Seventeen patients with different diagnoses resulting in condylar hypomobility (8 patients; 15 joints) and condylar instability (9 patients; 12 joints) had undergone alloplastic TMJ reconstruction. Maximum voluntary bite force and MIO were measured at pre-operatively (T0), 2 (T1), 6 (T2) and 12 (T3) months. For ordinal data comparison at different time-points, the Wilcoxon signed-ranks test was used. There was a significant improvement in maximum voluntary bite force for both, patients with condylar hypomobility (P = 0.003) and condylar instability (P = 0.007). Analysis of MIO revealed a significant improvement at T3 (P = 0.002). Alloplastic TJR would appear to increase maximum voluntary bite force and MIO. Biomechanical integrity of the stomatognathic system and the ability of the patient to triturate food could be improved by alloplastic temporomandibular joint (TMJ) replacement.


[Educational and nutritional study on the reduction of myocardial-infarct risk].
The study aims to establish whether recovery from myocardial infarction is the strongest or, alternatively, the only motivation toward changing unhealthy habits of living and eating and to what extent such patients and overtly healthy persons are prepared to receive advice to take measures to prevent myocardial infarction.


Role of endoscopic ultrasound in the diagnosis of agenesis of the dorsal pancreas.
Complete agenesis of the dorsal pancreas is an unusual congenital anomaly. Nowadays, the diagnosis is based on four imaging studies: transabdominal ultrasonography, computed tomography, magnetic resonance cholangiopancreatography and, the gold-standard, endoscopic retrograde cholangiopancreatography. Sometimes the ability of these studies are limited to distinguishing agenesis of the dorsal pancreas from other congenital abnormalities. Endoscopic ultrasound is a minimally invasive technique which permits us to obtain high resolution images of the pancreatic parenchyma and ductal system. We report the case of a 23-year-old woman with recurrent episodes of acute pancreatitis and non-conclusive classic imaging studies. Complete agenesis of the dorsal pancreas was demonstrated by endoscopic ultrasound. Endoscopic ultrasound may be useful in the diagnosis of agenesis of the dorsal pancreas.


Effect of temperature on the infectivity of Sarcocystis miescheriana cysts in pork.
Sarcocysts of Sarcocystis miescheriana in the thigh muscles of pigs became non-infective to pups after heating infected pork in minute pieces at 60 degrees C for 20 min, 70 degrees C for 15 min and 100 degrees C for 5 min. Similar pieces of infected muscle tissues, when exposed to -4 degrees C for 2 days or -20 degrees C for 1 day, became non-infective to pups. The experiment suggests that pork containing sarcocysts of S. miescheriana, and possibly of S. suihominis, requires cooking at a minimum of 70 degrees C for 15 min or freezing at -4 degrees C for 2 days or -20 degrees C for 1 day for making it safe for consumption.


Comparison of three molecular assays for detection of enteric viruses in stool samples.
Three molecular assays (FTD® Viral GE from Fast-track diagnostics, RIDA®GENE VSP1 from R-Biopharm, and Xpert Norovirus from Cepheid) were compared for virus detection in acute diarrhea samples. RIDA®GENE and FTD® Viral GE showed perfect/almost perfect agreement for Rotavirus, Sapovirus and Norovirus, substantial agreement for Adenovirus, and moderate agreement for Astrovirus.


Do Spanish patients drink alcohol while undergoing treatment with benzodiazepines?
In this study, we analyzed patterns of combined benzodiazepines and alcohol use among the Spanish general population over the age of 16 years. The study was based on information from the 1997 Spanish National Household Health Survey. A total of 6,396 persons over 16 years of age, a representative sample of noninstitutionalized Spaniards, were surveyed. One percent of the population are consumers of benzodiazepines and daily drinkers of alcohol; fundamentally, these consumers are men, of whom 15.4% drink alcohol at a high level (>50 units/week). Findings show the frequency of concurrent use of benzodiazepines and alcohol by the Spanish population.


Early career opportunities and practice characteristics of recent graduates of shoulder and elbow fellowship programs.
There exists anecdotal evidence that influential faculty members actively dissuade orthopedic surgery residents from pursuing a fellowship in shoulder and elbow due to a perceived lack of availability of jobs following graduation. The aims of the present study are to evaluate whether this perception is true by characterizing the early career opportunities and practice characteristics of recent graduates of shoulder and elbow fellowship programs through a survey of graduates of the past 5 years. An anonymous 39-question survey was designed and approved by the leadership of the American Shoulder and Elbow Surgeons (ASES). The survey was distributed via electronic mail to the fellowship directors and coordinators of the 31 ASES-recognized shoulder and elbow fellowship programs. The fellowship directors and coordinators then sent the survey to the shoulder and elbow fellowship graduates of the last 5 years (2016-2020). Following a total of 4 emails, the survey closed after 8 weeks, and descriptive statistical analysis was performed. Seventy-six of 171 (44.4%) fellows responded. In total, 89.5% were very or somewhat satisfied with their fellowship experience, and 90.8% would pursue a shoulder and elbow fellowship again. Notably, 100% of shoulder and elbow fellowship graduates surveyed in the past 5 years have secured employment. The average number of total orthopedic and shoulder and elbow cases performed annually was 296.7 (SD 141.3) and 173.9 (SD 120.2), respectively. In addition, 62.7% and 89% of respondents were very or somewhat satisfied with the volume and surgical complexity of shoulder and elbow cases, respectively. For the fellows that believed their case experience to be inadequate, the most common reasons were competition from other practices (66.0%) and inadequate patient volume (59.6%). Recent graduates of the ASES-recognized shoulder and elbow fellowship programs demonstrate a high level of satisfaction with the fellowship and their subspeciality selection. The majority of fellows believed that completing a shoulder and elbow fellowship enhanced their job opportunities. Altogether, there are ample job opportunities and high satisfaction with the volume and complexity of cases as an early career shoulder and elbow surgeon.


Associational plant refuges: convergent patterns in marine and terrestrial communities result from differing mechanisms.
An associational plant refuge occurs when a plant that is susceptible to herbivory gains protection from herbivory when it is associated with another plant. In coastal North Carolina, the abundance of the palatable red alga Gracilaria tikvahiae is positively correlated with the abundance of the unpalatable brown alga Sargassum filipendula during times of increased herbivore activity. To see if grazing by the sea urchin Arbacia punctulata could generate this pattern, controlled experiments were conducted in out-door microcosms and in the laboratory. Gracilaria beneath a canopy of Sargassum was eaten significantly less than Gracilaria alone. When Arbacia were excluded, Gracilaria alone grew significantly more than Gracilaria beneath Sargassum, demonstrating that Sargassum is a competitor of Gracilaria. Experiments investigating Sargassum's deterrent role indicated that Sargassum decreased the foraging range of Arbacia and the rate at which it fed on Gracilaria. Additional experiments with plastic Sargassum mimics indicated that the decreased grazing on Gracilaria was not a result of Sargassum morphology, but was probably attributable to some chemical characteristic of Sargassum. The pattern of increased grazing in monocultures (only Gracilaria present) versus polycultures (both Gracilaria and Sargassum present) demonstrated in this study also has been demonstrated for plant-insect interactions in terrestrial communities. In these communities, insect density is higher in monocultures than in polycultures because insects find and immigrate to monocultures more rapidly, and once in a monoculture, they emigrate from them less often than from polycultures. In this study, urchins did not find and immigrate to monocultures more rapidly, nor did they tend to stay in them once they were found; in fact, they emigrated from monocultures of Gracilaria more rapidly than from Gracilaria and Sargassum polycultures. Increased grazing in Gracilaria monocultures resulted from increased rates of movement and feeding of individual herbivores, not from increased herbivore density as has been reported for terrestrial systems.


Prophylaxis with whole gut irrigation and antimicrobials in colorectal surgery. A prospective, randomized double-blind clinical trial.
In a prospective, randomized double-blind trial, the efficacy of whole gut irrigation as preoperative bowel preparation for elective colorectal surgery was evaluated alone and in combination with two antimicrobial agents in 148 patients. The antimicrobial regimens were metronidazole alone or metronidazole and ampicillin administered systemically preoperatively and continued for 3 days. Whole gut irrigation was completed without any discomfort in 87 percent of the patients. In 3 percent, the irrigation was stopped and the patients were excluded from the study. Abdominal wound infection developed in 32 percent of the patients after whole gut irrigation, and the addition of metronidazole decreased this incidence to 22 percent (not significant). The incidence in wound infections in the group receiving metronidazole as well as ampicillin was 2 percent, and this difference was highly significant compared with both other groups. No significant difference was found for the incidence of intraabdominal abscesses (p = 0.06), infection of the perineal wound, or anastomotic leakage. No difference in the postoperative infection rate was found between a bowel containing fecal fluid or fecal masses, but when a bowel was clean, significantly fewer infectious complications were found. Whole gut irrigation is a rapid, well-tolerated, easily performed, and safe form of preoperative bowel preparation in elective colorectal surgery if combined with systemic antimicrobial prophylaxis consisting of antimicrobial agents effective against anaerobic and aerobic organisms.


Poor sleep quality and associated factors among HIV-positive pregnant women in Northwest, Ethiopia: a facility-based, cross-sectional study.
Poor sleep quality during pregnancy might have an impact on adverse birth outcomes like premature rupture of membrane, preterm birth, lifelong neurocognitive impairment, low birth weight, and increased the risk of neonatal morbidity and mortality. In Ethiopia, the magnitude of poor sleep quality among this group of people is extremely limited. So, this study aims to determine the magnitude of poor sleep quality and its associated factors among HIV-positive pregnant women attending public hospitals in Northwest Ethiopia. An institution-based cross-sectional study was done using a simple random sampling technique to recruit 411 HIV-positive pregnant women from January to March; 2021. Sleep quality over the last 1 month was measured using the Pittsburgh Sleep Quality Index (PSQI). General anxiety disorder (GAD-7), Sleep Hygiene Index (SHI), and List of Threatening of Experiences (LTE) instruments were used to identify factors associated with poor sleep quality. Bivariate and multivariable logistic regression with odds ratio and 95% CI were employed to identify determinant factors of poor sleep quality. Statistical significance association was declared at P-value < 0.05. A total of 411 out of 423 HIV-positive pregnant women were interviewed, with a response rate of 97.1%. The overall magnitude of poor sleep quality among HIV-positive pregnant was found to be 39.4% with a 95% of confidence interval (CI) (34.3, 44.3). Stressful life events, [AOR = 3.10, 95% CI (1.60, 6.01)], having comorbid general anxiety symptoms [AOR = 2.46, 95% CI (1.58, 3.81)], unplanned pregnancy [AOR = 2.18, 95% CI (1.20, 3.96)], and poor sleep hygiene practice [AOR = 2.23, 95% CI (1.21, 4.10)] were significantly associated with poor quality of sleep. The overall magnitude of poor sleep quality among HIV-positive pregnant women was high. Stressful life events, poor sleep hygiene, unplanned pregnancy, and comorbid general anxiety symptoms were the determinant factors of poor sleep quality that should be taken high consideration for early detection and appropriate intervention for poor sleep quality in HIV-positive pregnant women.


Ureteric vasculitis, an unusual presentation of polyarteritis nodosa: a case report.
A 22 year old female presented with vasculitic skin rash. She was incidentally found to be hypertensive and had proteinuria. Skin biopsy showed leuco-cytoclastic vasculitis. On Imaging, there was left hydronephrosis, hydroureter with bilateral multiple foci of ureteric stenosis and micro-aneurysms in relation to interlobar arteries of kidney. A diagnosis of classical Polyarteritis Nodosa (cPAN) with multi-level ureteric stenosis was made. She was treated with Glucocorticoids, Cyclophosphamide, following which Azathioprine was given.


Effects of Dexmedetomidine on Postoperative Nausea and Vomiting in Adult Patients Undergoing Ambulatory Thyroidectomy: A Randomized Clinical Trial.
Background: Postoperative nausea and vomiting (PONV) is a common and disturbing problem in patients undergoing ambulatory thyroidectomy. This prospective trial aimed to explore whether dexmedetomidine (DEX) combined with azasetron (AZA) can further drop the incidence of PONV in patients undergoing ambulatory thyroidectomy compared with AZA. Methods: This single-center, randomized, double-blind trial involved 172 adult patients undergoing ambulatory thyroidectomy. The individuals were randomized to DEX + AZA group and AZA group. In the DEX + AZA group, patients received dexmedetomidine 0.5 μg kg-1 for 10 min and then the infusion rate was held at 0.1 μg kg-1 h-1 until the completion of the operation, while the same amount of 0.9% saline in the AZA group. At the completion of the surgery, 10 mg azasetron was administered to every patient in both groups. The primary outcome was the incidence of 24 h PONV after ambulatory thyroidectomy. The secondary outcomes included residence time in recovery room, pain scores, severity of nausea, and adverse events. Results: No significant difference was found in the incidence of 24-h PONV between the DEX + AZA group and the AZA group [36% (30 of 84) vs. 38% (32 of 84); relative risk, 0.94; 95% confidence interval (CI), 0.63-1.40; P = 0.749]. The incidence of severe nausea was similar between the DEX + AZA group and the AZA group [57% (12 of 21) vs. 43% (9 of 21); relative risk, 1.33; 95% CI, 0.72-2.50; P = 0.355]. Conclusions: Intraoperative dexmedetomidine combined with azasetron failed to drop the incidence of 24-h PONV compared with azasetron alone in patients undergoing ambulatory thyroidectomy.


Possible involvement of nitric oxide in the progression of diabetic retinopathy.
Abnormal nitric oxide (NO) synthesis has been implicated in the pathogenesis of diabetes mellitus. The aim of our study was to elucidate the relationship between the stages of diabetic retinopathy (DR) and the NO levels in aqueous humor and plasma. Using the chemiluminescence assay, we measured the concentrations of NO in aqueous humor and plasma samples obtained during intraocular surgery from 45 diabetic patients and 19 nondiabetic cataract patients. The patients with diabetes were classified into 4 groups: proliferative DR (PDR) with active neovascularization (active PDR; 9 cases), PDR with quiescent neovascularization (regressed PDR; 6 cases), background DR (BDR; 16 cases) and no DR (14 cases). We found that the aqueous NO levels (mean +/- SE) of the active PDR group (83.2 +/- 13.9 microM) were significantly higher than those of the BDR group (45.8 +/- 6.0 microM, p = 0.049) and the diabetics without DR (33.3 +/- 5.2 microM, p = 0.011), and, although not statistically significantly, they were also higher than those of the regressed PDR group (52.1 +/- 10.3 microM, p = 0.224). However, no significant differences were observed between any of the diabetic subgroups in the plasma NO levels (p = 0.345). We therefore concluded that NO present in the ocular tissues may play important roles in the progression of DR.


Wood and humus decay strategies by white-rot basidiomycetes correlate with two different dye decolorization and enzyme secretion patterns on agar plates.
During several forays for ligninolytic fungi in different Spanish native forests, 35 white-rot basidiomycetes growing on dead wood (16 species from 12 genera) and leaf litter (19 species from 10 genera) were selected for their ability to decolorize two recalcitrant aromatic dyes (Reactive Blue 38 and Reactive Black 5) added to malt extract agar medium. In this study, two dye decolorization patterns were observed and correlated with two ecophysiological groups (wood and humus white-rot basidiomycetes) and three taxonomical groups (orders Polyporales, Hymenochaetales and Agaricales). Depending on the above groups, different decolorization zones were observed on the dye-containing plates, being restricted to the colony area or extending to the surrounding medium, which suggested two different decay strategies. These two strategies were related to the ability to secrete peroxidases and laccases inside (white-rot wood Polyporales, Hymenochaetales and Agaricales) and outside (white-rot humus Agaricales) of the fungal colony, as revealed by enzymatic tests performed directly on the agar plates. Similar oxidoreductases production patterns were observed when fungi were grown in the absence of dyes, although the set of enzyme released was different. All these results suggest that the decolorization patterns observed could be related with the existence of two decay strategies developed by white-rot basidiomycetes adapted to wood and leaf litter decay in the field.


Metabolomics of bronchopulmonary dysplasia.
The pathogenesis of Bronchopulmonary dysplasia (BPD) remains poorly understood. It is a multifactorial disease having a genetic-environmental basis. Although attempts have been made to identify a biomarker, none have been validated for clinical use to date. Metabolomics is a promising field of the "omics technologies" that could allow for better understanding of the pathogenesis and underlying mechanisms of BPD as well as facilitate detection of biomarkers. Identification of these biomarkers would improve diagnosis, identify patients in early disease stages and potentially target intervention. This review focuses on the evidence arising from metabolomics and its interaction with microbiomics and pharmacology with respect to pathogenesis and treatment options for this multifactorial complex disease.


Genome-scale transcriptomic insights into the gene co-expression network of seed abortion in triploid Siraitia grosvenorii.
Siraitia grosvenorii (Swingle) C. Jeffrey, also known as Luohanguo or monk fruit, is a famous traditional Chinese medicine ingredient with important medicinal value and broad development prospects. Diploid S. grosvenorii has too many seeds, which will increase the utilization cost of active ingredients. Thus, studying the molecular mechanism of seed abortion in triploid S. grosvenorii, identifying the abortion-related genes, and regulating their expression will be a new direction to obtain seedless S. grosvenorii. Herein, we examined the submicroscopic structure of triploid S. grosvenorii seeds during abortion. Upon measuring the endogenous hormone content, we found that abscisic acid (ABA) and trans-zeatin (ZR) levels were significantly downregulated after days 15 and 20 of flowering. RNA sequencing of triploid seeds at different developmental stages was performed to identify key genes regulating abortion in triploid S. grosvenorii seeds. Multiple genes with differential expression between adjacent stages were identified; seven genes were differentially expressed across all stages. Weight gene co-expression network analysis revealed that the enhancement of monoterpene and terpene metabolic processes might lead to seed abortion by reducing the substrate flow to ABA and ZR. These findings provide insights into the gene-regulatory network of seed abortion in triploid S. grosvenorii from different perspectives, thereby facilitating the innovation of the breeding technology of S. grosvenorii.


Insect and arthropod conservation policies: the need for a paradigm shift.
To date, insect conservation policy mainly consists of species protection lists, with some requiring habitat or ecosystem preservation to protect insect ecology. While a landscape or habitat approach seems the most appropriate for insect conservation, cases are rare of protected areas designated specifically for insects or other arthropods. Moreover, neither of these conservation approaches (species or habitat protection) have halted the worldwide decline in insects: species protection lists and reserves at best serve as band-aids for a massive hemorrhage. The main drivers of insect decline (global changes) are only loosely addressed by national and international policies. So, if we know the causes, what stands in the way of prevention and treatment for the problem? To save insects, our civilization needs psychotherapy rather than first-aid gestures: a paradigm shift that would place value on insects, and give rise to ecocentric policies informed by a wide range of stakeholders.


Assessment and estimation of 65Zn production yield via neutron induced reaction on natZnO and natZnONPs.
Zinc-65 has been of great interest in medical, biomedical, agricultural, and industrial applications due to its suitable half-life and decay properties. The 65Zn was produced via neutron irradiation on natural zinc oxide and natural zinc oxide nanoparticles targets in Tehran Research Reactor (TRR) at a thermal neutron flux of 4.5 × 1013 n cm-2 s-1 for 30 min. The excitation function of 64Zn(n,γ)65Zn reaction was calculated via the TALYS-1.8 code. The MCNPX code was used to calculate the thermal neutron distribution. The 65Zn theoretical production yield was estimated using calculated cross sections and the calculated thermal neutron distribution. The obtained experimental data and simulated value of production yield for 65Zn were in reasonable agreement.


Structure, function and interactions of the PufX protein.
The PufX protein is an important component of the reaction centre-light-harvesting 1 (RC-LH1) complex of Rhodobacter species of purple photosynthetic bacteria. Early studies showed that removal of the PufX protein causes changes in the structure of the RC-LH1 complex that result in a loss of the capacity for photosynthetic growth, and that this loss can be overcome though further mutations that change the structure of the LH1 antenna. More recent studies have examined interactions of the PufX protein with other components of the RC-LH1 complex. This review considers our current understanding of the structure and function of the PufX protein, how this protein interacts with other components of the photosynthetic membrane, and its influence on the oligomeric state of the RC-LH1 complex and the larger-scale architecture of the photosynthetic membrane.


Visceral adipose tissue specific persistence of Mycobacterium tuberculosis may be reason for the metabolic syndrome.
Mycobacterium tuberculosis (Mtb) is highly successful intracellular pathogen. Infection is maintained in spite of acquired immunity and resists eradication by antimicrobials. Following bacillaemia, small numbers of bacteria are disseminated to the extrapulmonary organs most likely including visceral adipose tissue by a mechanism that may involve the migration of M. tuberculosis within dendritic cells. In this lipid rich environment, Mtb can metabolize the fatty acids in a glyoxylate cycle dependent manner, and a state of chronic persistence may ensue. The persistent bacilli primarily use fatty acids as their carbon source. Expression of isocitrate lyase (ICL), gating enzyme of glyoxylate cycle, is upregulated during infection. ICL is important for survival during the persistent phase of infection. Expression of adipokines, particularly monocyte chemoattractant protein-1 (MCP-1), which is a potent proinflammatory cytokine, may be increased. MCP-1 contributes both to the recruitment of macrophages to adipose tissue and to the development of insulin resistance in humans. In addition, prolonged low level immune stimulation induces local adipolipogenesis, increasing visceral fat. Increased delivery of free fatty acid to the liver may stimulate the glyoxylate cycle-induced gluconeogenesis, raising hepatic glucose output. Hence, inhibition of the triggering enzyme ICL, which initiates all the pathologies related to persistent Mtb infection, may block the growth of the bacteria and may resolve the systemic metabolic complications.


Chemopreventive Agents After Pancreatic Resection for Ductal Adenocarcinoma: Legend or Scientific Evidence?
Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related death in the USA. A wealth of evidence has demonstrated the chemopreventive activity of aspirin, statins, and metformin against PDAC. The aim of this study is to investigate the effect of aspirin, statins, and metformin on disease-free survival (DFS) and disease-specific survival (DSS) in a large population of PDAC patients undergoing pancreatic resection. All patients who underwent pancreatic resections between January 2015 and September 2018 were retrospectively reviewed. The potentially "chemopreventive agents" considered for the analysis were aspirin, statins, and metformin. Drug use was defined in case of regular assumption at least 6 months before diagnosis and regularly after surgery along the follow-up period. A total of 430 patients were enrolled in this study, with median DFS and DSS of 21 months (IQR 13-30) months and 34 (IQR 26-52) months, respectively. On multivariable analysis, use of aspirin was associated with better DFS (HR: 0.62; p = 0.038). Metformin was associated with better DFS, without reaching statistical significance (p = 0.083). Use of statins did not influence DFS in the studied population. Aspirin, metformin, and statins were not associated with better DSS on multivariable analysis. Factors influencing DSS were pT3/pT4, N1, N2, no adjuvant treatment, G3, and ASA score > 3. The results suggest that chronic use of aspirin is associated with increased DFS but not with better DSS after surgical resection in patients with PDAC.


Unprecedented gallium-nitrogen anions: synthesis and characterization of [(Cl3Ga)3N]3- and [(Cl3Ga)2NSnMe3]2-.
The [(Cl3Ga)3N](3-) (1) anion, which is the sole example of a discrete chemical species containing a μ3-N atom bound only to gallium, was isolated from the reaction of Cl3Ga·N(SnMe3)3 with [GaCl4](1-). The analogous reaction of [GaCl4](1-) with (Me3Sn)3N afforded [(Cl3Ga)2NSnMe3](2-) (2), which is also an unprecedented anion containing a single μ3-N atom bound to only gallium and tin.


Heat shock protein expression in cerebral X-linked adrenoleukodystrophy reveals astrocyte stress prior to myelin loss.
X-linked adrenoleukodystrophy (X-ALD) is a genetic white matter disorder in which demyelination occurs due to accumulation of very long-chain fatty acids. Inflammation in the brain white matter is a hallmark of the pathology of cerebral X-ALD, but the underlying pathogenic mechanisms are still largely unknown. In other inflammatory demyelinating disorders, such as multiple sclerosis, the expression of heat shock proteins (HSPs) in combination with interferon-γ (IFN-γ) has been suggested to play a prominent role in the initiation of demyelination and inflammation. We therefore investigated these pathways in X-ALD lesions. By immunohistochemistry, we examined the expression of small HSPs (HSPB1, HSPB5, HSPB6, HSPB8) and higher molecular weight HSPs (HSPA, HSPD1), and the expression of elements of the IFN-γ pathway on autopsy material of five patients with X-ALD. The expression of the larger HSPs, HSPA and HSPD1, as well as small HSPs is increased in X-ALD lesions compared with normal-appearing white matter. Such upregulation can already be detected before demyelination and inflammation occur, and it is predominant in astrocytes. The IFN-γ pathway does not seem to play a leading role in the observed inflammation. The finding that astrocytes show signs of cellular stress before demyelination suggests that they play a major role early in the pathogenesis of cerebral X-ALD, and may therefore be involved in the initiation of inflammation and demyelination.


[Lipectomy and lipexhaeresia in the area of the lower extremities (author's transl)].
Lokalized fat can be removed for pathologic but also for purely aesthetic reasons. Lipexhaeresia is a method that enables one to do this without leaving any significant scars. Certain principles of approach must be observed if aesthetically satisfactory results are to be obtained. Experience shows that there are no limits as to indication. Combination with dermolipectomy in the area of the buttocks increases the range of application.


Non-linear relationship of gamma-glutamyl transpeptidase to lymphocyte count ratio with the recurrence of hepatocellular carcinoma with staging I-II: a retrospective cohort study.
High recurrence rate was a major factor for the poor postoperative prognosis of hepatocellular carcinoma (HCC) patients. The present study was intended to evaluate the association of gamma-glutamyl transpeptidase to lymphocyte count ratio (GLR) and the recurrence of HCC with staging I-II in Chinese. The retrospective cohort data was derived from the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2018 on 496 patients who underwent radical resection of HCC with staging I-II. Multivariable Cox regression models were used to determine hazard ratios (HR) and 95% confidence interval (CI) for the recurrence of HCC with staging I-II of each GLR tertile category. The restricted cubic spline model was used to find out the threshold effect. With the low tertile of GLR as the reference, multivariable-adjusted HR and 95% CI of the middle and high tertile categories were 1.748 (1.170-2.612) and 2.078 (1.339-3.227). In addition, there was a positive correlation (HR 1.002; 95% CI 1.001-1.004) and a non-liner relationship was found, whose point was 27.5. When the GLR was less than 27.5, the risk of recurrence increased, obviously with the increase in GLR levels (HR 1.041; 95% CI 1.014-1.068). The GLR was independently associated with the recurrence of HCC patients with staging I-II. Furthermore, the relationship was positive and no-linear.


Detection of breast cancer cells by a near-infrared fluorescent probe targeting mitochondrial viscosity.
Monitoring abnormal viscosity in biological systems is important for basic research and clinical applications. Fluorescence imaging technology is adaptable for the visualization of tumor tissues due to its comprehensive features. However, fluorescence detection of intracellular viscosity in clinical samples remains challenging. We developed a promising near-infrared fluorescent probe, M556, for viscosity measurement. M556, which targets mitochondria, was successfully applied to monitor the mitochondrial viscosity in living cells. Furthermore, M556 was demonstrated to effectively discriminate tumors from normal tissues in a mouse tumor model and in clinical specimens from breast cancer patients, thus indicating the potential perioperative use of this probe by clinicians to assist with biopsy procedures.


Localization of calcitonin gene-related peptide in the vestibular end-organs in the rat: an immunohistochemical study.
The present immunocytochemical study has demonstrated the presence of a dense fiber plexus containing calcitonin gene-related peptide (CGRP) in the vestibular end-organs in the rat. These fibers appear to originate from the central nervous system.


Competitive exclusion and coexistence for pathogens in an epidemic model with variable population size.
We study an SIR epidemic model with a variable host population size. We prove that if the model parameters satisfy certain inequalities then competition between n pathogens for a single host leads to exclusion of all pathogens except the one with the largest basic reproduction number. It is shown that a knowledge of the basic reproduction numbers is necessary but not sufficient for determining competitive exclusion. Numerical results illustrate that these inequalities are sufficient but not necessary for competitive exclusion to occur. In addition, an example is given which shows that if such inequalities are not satisfied then coexistence may occur.


Metabolism of triphenylmethane colours II. Absorption, excretion and distribution of Benzyl Violet 4B (FD and C Violet No. 1) in rats.
Absorption, excretion and distribution of Benzyl Violet 4B were investigated in rats, deterimining the colour by the 2-wavelength technique. This colour was hardly absorbed when given orally; only 0.89% of the dose was recovered from the bile after 24 h. On the other hand, it was rapidly excreted through the bile when given intravenously; the cumulative recovery of biliary excretion amounted to 88.4% at 4 h and 95.9% at 24 h. The levels of the colour distributed in the liver, kidney abdominal muscle and blood serum were in the range of 1--3 microgram/g of tissue in rats fed a diet containing 5% Benzyl Violet 4B for 8 weeks, whereas they were slightly lower in rats fed the diet for 18 weeks. When rats were given the colour intravenously, there was no sex-related difference in the distribution of the colour in either Wistar or Sprague--Dawley rats, but the disappearance of the colour from the brain, liver, abdominal muscle, abdominal skin and ear of Sprague--Dawley rats was slower than from those of Wistar rats.


A comparative study of extraction apparatus in HPLC analysis of ochratoxin A in muscle.
Ochratoxin A (OTA) is a secondary fungal metabolite produced by several moulds, mainly by Aspergillus ochraceus and by Penicillium verrucosum, that occurs in meat products. The aim of this work was to optimize an efficient extraction procedure for the determination of OTA in muscle tissue in order to assess its occurrence in meat samples. Three different apparatus, a Waring blender, a switching apparatus, and an ultrasonic processor, were evaluated to verify the efficiency of extraction. The analytical methods proposed involve the extraction with chloroform-orthophosphoric acid, cleanup through an immunoaffinity column, high-performance liquid chromatography/fluorescence detection for separation and identification of OTA, and confirmation with liquid chromatography/FD after methylation of OTA in muscle tissue. The limit of quantification of the proposed method was 0.04 microg kg(-1). Recoveries of OTA, using switching apparatus, ranged from 90.3 to 103.2% for chicken muscle spiked at 2.4 and 0.48 microg kg(-1), respectively, with a within-day relative standard deviation of 17 and 15.3%. The proposed method was applied to 38 chicken, swine, and turkey muscle samples and the presence of OTA was confirmed in five samples. Finally, the estimated daily intake of OTA in this study was between 23 pg kg(-1) body weight per day for swine samples and 18 pg kg(-1) body weight per day for turkey samples.


The transforming protein of the MC29-related virus CMII is a nuclear DNA-binding protein whereas MH2 codes for a cytoplasmic RNA-DNA binding polyprotein.
The acute avian leukemia viruses MH2 and CMII belong to the group of avian myelocytomatosis viruses, the prototype virus of which is MC29. This group of viruses is characterized by myc-specific oncogenes which are presumably expressed as gag-myc polyproteins. These polyproteins are synthesized in non-producer cells transformed by MH2 and CMII and have mol. wts. of 100 000 (p100) and 90 000 (p90), respectively. Monoclonal antibodies against the N terminus of gag, p19, were used to localize the protein in MH2- and CMII-transformed non-producer fibroblasts. Immunofluorescence and cell fractionation indicated that greater than 90% of p100 from MH2 was located in the cytoplasm, whereas greater than 70% of p90 from CMII resided in the nucleus. Isolation of p100 and p90 by immunoaffinity chromatography resulted in an approximately 2000-fold purification of the two polyproteins. Both of them, as well as p110 of MC29, bound to double-stranded DNA of chick fibroblasts in vitro. However, only the MH2-specific polyprotein p100 bound to RNA in vitro. Such a binding was not observed for p90 or p110, or for the purified gag precursor Pr76. Another polyprotein, gag-erbA, from avian erythroblastosis virus, which is also located in the cytoplasm, did not bind to RNA. Our results indicate that the CMII-specific polyprotein p90 behaved indistinguishably from the p110 of MC29. However, the MH2-specific polyprotein p100 exhibited unique and novel properties which were distinct from a gag-myc-type protein.


Relationship of obesity to diabetes: influence of obesity level and body fat distribution.
The relationship of clinical diabetes to body fat distribution and obesity level was examined in 15,532 women. After adjusting for relative weight, all upper body segment girth measurements (neck, bust, and waist) had strong positive associations with diabetes. In contrast, the lower body segment girth measurement (hips) had an equally strong but inverse association with diabetes. Based upon waist-to-hip girth ratio, women were divided into four subgroups. The prevalence of diabetes increased with increasing values of this ratio. Women in the upper quartile had about three times the prevalence of diabetes as women of comparable obesity level in the lowest quartile. Women with both upper body fat predominance and severe obesity had a relative risk of diabetes 10.3 times as great as nonobese subjects with lower body fat predominance. The results suggest that localization of fat in the upper body segment and severe obesity are two distinct additive risks for diabetes.


Persistent binocular diplopia after cataract surgery.
We reviewed the records of 38 consecutive patients who had persistent binocular diplopia after cataract surgery. The patients were divided into ten categories based on the suspected conditions underlying the diplopia. Of 16 patients who underwent strabismus surgery, five achieved the therapeutic goal of single binocular vision in the primary and reading position, and four attained this with prismatic or botulinum toxin therapy in addition to surgery. Seven patients continued to have diplopia despite strabismus surgery and adjunctive therapy. Even small residual deviations were often intolerable, because of highly diminished fusional amplitudes.


Synergistic actions of insulin-sensitive and Sirt1-mediated pathways in the differentiation of mouse embryonic stem cells to osteoblast.
Murine embryonic stem cells (mESCs) have the potential to differentiate into almost any type of cell, and hence, represent a useful biological resource for tissue engineering. The differentiation of mESCs into osteoblasts in vitro is usually dampened by simultaneous differentiation of adipocytes. Insulin exerts a profound effect on bone development through increased differentiation of osteoblasts and concurrent formation of adipocytes. Comparatively, Sirt1, which plays a crucial role in osteoblast differentiation, has been reported to down regulate adipocyte formation during osteoblast differentiation. This study analyzed the combined effects of insulin and Sirt1 on the differentiation of osteoblasts. Osteoblast differentiation was quantified by estimating the accumulation of mineralized matrix and expression of osteogenic genes. The present data show that the simultaneous action of the insulin and Sirt1-mediated pathways increased the efficiency of osteoblast differentiation. When the cells were tested for ALP activity and Alizarin red staining, there was a respective increase of ~180% and ~166% (P<0.05) compared to the control. Furthermore, the mRNA expression patterns of osteoprotegerin, osterix, runx2, and osteopontin were increased by 3.6, 2.3, 1.8, and 1.7-fold, respectively, with a concomitant decrease in the mRNA expression levels of adipocyte marker genes. Interestingly, blocking the effects of both Sirt1 and insulin resulted in decreased osteoblastogenesis (60%) and subsequent increased adipocyte differentiation (195%) (P<0.05). Moreover, immunoblotting analysis demonstrated that this activation was via an Akt-dependent pathway. In conclusion, the present data suggests an enhanced process of osteoblast differentiation that can be exploited further to improve mESC differentiation.


Tako Tsubo cardiomyopathy in a patient with antiphosholipid syndrome secondary to systemic lupus erythemathosus (SLE).
Tako Tsubo cardiomyopathy is rare, stress related and indistinguishable from acute myocardial infarction clinically. Proper diagnosis is essential to avoid unnecessary thrombolysis and life long management of coronary artery disease.


Experimental study on anisotropy of hydraulic conductivity for municipal solid waste.
Anisotropy of hydraulic conductivity is an important parameter controlling fluid movement in municipal solid waste (MSW) landfills, while measurements of anisotropy are rare. In this study, a laboratory-scale enhanced reactor was built to create MSW samples with different degrees of degradation. Vertical and horizontal hydraulic conductivities of these samples were measured in a self-designed permeameter to study the effects of compression and degradation on anisotropy of MSW. CT scanning was performed to observe the internal pore-structure of MSW under compression. A prediction model of anisotropy under compression was established. It was found that as degradation time increased from 0 month to 18 months, the dry mass percent of 0D particles increased from 12.3% to 38.8%, while 2D particles content decreased from 78.7% to 47.2%. As vertical stress increased from 50 kPa to 400 kPa, dry unit weight (γd) increased from 3.26 kN/m3 to 5.51 kN/m3, anisotropy (A) increased from 1.26 to 5.17. It was because that the size and continuity of pores decreased and the angle of pore arrangement tended to be horizontal as the vertical stress increased. The relation between anisotropy and vertical stress could be well fitted with the prediction model. When degradation time increased from 0 month to 18 months, A decreased linearly from 5.02 to 2.75 due to the decreasing content of 2D particles. Anisotropy also decreased with the decreasing C/L. Compression has much greater influence on waste anisotropy than that of degradation. Anisotropy of MSW at different depths of landfills could be determined based on the trend lines in this study.


Immunoablative high-dose cyclophosphamide without stem-cell rescue for refractory, severe autoimmune disease.
Immunoablative high-dose cyclophosphamide without stem-cell rescue induces durable, complete remission in most patients with aplastic anemia. To determine the efficacy of high-dose cyclophosphamide in various refractory, severe autoimmune diseases. Prospective phase II study. Johns Hopkins University (Baltimore, Maryland) and Hahnemann University (Philadelphia, Pennsylvania). Eight patients with refractory, severe autoimmune disease. Immunoablative high-dose cyclophosphamide (50 mg/kg of body weight per day) for 4 consecutive days. Clinical and laboratory variables of autoimmune disease. Seven patients improved markedly: Five achieved complete remission and two achieved partial remission. Four patients have remained in continuous complete remission for 3 to 21 months, and two patients in partial remission continue to improve after 14 and 19 months of follow-up. High-dose cyclophosphamide was well tolerated; median times to a neutrophil count of 0.5 x 10(9) cells/L and platelet transfusion independence were 17 and 16 days, respectively. Immunoablative high-dose cyclophosphamide without stem-cell rescue can induce complete remission in patients with refractory, severe autoimmune disease. Reemergence of marrow function is similar to that seen after autologous transplantation and does not carry the risk for reinfusion of autoaggressive lymphocytes with the autograft.


Building a FAIR image data ecosystem for microscopy communities.
Bioimaging has now entered the era of big data with faster-than-ever development of complex microscopy technologies leading to increasingly complex datasets. This enormous increase in data size and informational complexity within those datasets has brought with it several difficulties in terms of common and harmonized data handling, analysis, and management practices, which are currently hampering the full potential of image data being realized. Here, we outline a wide range of efforts and solutions currently being developed by the microscopy community to address these challenges on the path towards FAIR bioimaging data. We also highlight how different actors in the microscopy ecosystem are working together, creating synergies that develop new approaches, and how research infrastructures, such as Euro-BioImaging, are fostering these interactions to shape the field.


Outcomes of endoscopic therapy in donation after cardiac death liver transplant biliary strictures.
Biliary strictures after donation-after-cardiac-death (DCD) liver transplantation (LT) require multiple endoscopic retrograde cholangiopancreatographies (ERCP). The outcomes of endoscopic dilation and maximal stenting are not well-characterized in this high-risk population. DCD LT recipients who underwent LT and ERCP from 2012-2018 were selected. Anastomotic and non-anastomotic strictures were treated with balloon dilation and maximal stenting. A successful stent-free trial was defined as absence of biochemical, clinical or imaging evidence of strictures on follow-up exceeding 6 months. Adverse events were defined as unplanned admission or inpatient evaluation within 7 days of ERCP. Forty-nine DCD LT recipients underwent ERCP and 34 patients were diagnosed with strictures (20 anastomotic). Stent-free trial was successful in 27 patients. Adverse events occurred after 20 ERCPs. Patients with anastomotic strictures required fewer stents (1.43 ± 1.37 vs 2.63 ± 1.66; P < 0.001), shorter procedure and fluoroscopy times (34.15 ± 20.9 vs 59.6 ± 30.7 minutes, P < 0.001; 5.99 ± 7.4 vs 14.73 ± 10.74 minutes, P < 0.001), fewer relapses (10% vs 57%, P = 0.003), shorter intervals between initial ERCP and stent-free success (136.9 ± 118.3 vs 399.56 ± 234.7; P = 0.003), and between LT and stent-free success (227.8 ± 171.9 vs 464.1 ± 224.6 days; P = 0.005) compared to non-anastomotic strictures. Endoscopic dilation and maximal stenting resolves biliary strictures in DCD LT recipients with sustained success and relatively few adverse events.


Supramolecular Ladder Assemblies as a Model for Probing Electronic Interactions between Multiple Stacked π-Conjugated Systems.
A series of mono-, di-, and tri-topic receptors in which H-bonding sites, complementary to those of barbituric acid (BA), are fused is used to induce the supramolecular assembly of n×m ladders containing 1, 2, or 3 triphenylenevinylene units appended with BA. The topological constraint enforced by the architectures induces through-space interactions between the electroactive moieties that are reflected in the electronic absorption and emission spectrum. The n=2, m=2 or m=3 architectures undergo two single electron oxidation events, indicative of the formation of the corresponding mono- and di-radical cation species with comproportionation constants of 340 and 70, respectively. Comparison of the electrochemical potentials suggests that the charges are delocalized over the electroactive units in the assembly.


On the Role of Temperature in the Depolymerization of PET by FAST-PETase: An Atomistic Point of View on Possible Active Site Pre-Organization and Substrate-Destabilization Effects.
Enzyme FAST-PETase, recently obtained by a machine learning approach, can depolymerize poly(ethylene terephthalate) (PET), a synthetic resin employed in plastics and in clothing fibers. Therefore it represents a promising solution for the recycling of PET-based materials. In this study, a model of PET was adopted to describe the substrate, and all-atoms classical molecular dynamics (MD) simulations on apo- and substrate-bound FAST-PETase were carried out at 30 and 50 °C to provide atomistic details on the binding step of the catalytic cycle. Comparative analysis shed light on the interactions occurring between the FAST-PETase and 4PET at 50 °C, the optimal working conditions of the enzyme. Pre-organization of the enzyme active and binding sites has been highlighted, while MD simulations of FAST-PETase:4PET pointed out the occurrence of solvent-inaccessible conformations of the substrate promoted by the enzyme. Indeed, neither of these conformations was observed during MD simulations of the substrate alone in solution performed at 30, 50 and 150 °C. The analysis led us to propose that, at 50 °C, the FAST-PETase is pre-organized to bind the PET and that the interactions occurring in the binding site can promote a more reactive conformation of PET substrate, thus enhancing the catalytic activity of the enzyme.


Six-year prognosis of diabetic patients with coronary artery disease.
Diabetes is associated with increased cardiovascular mortality. The aim of our study was to determine the prognostic factors for mortality in patients with type 2 diabetes (T2DM) and coronary artery disease (CAD) who underwent coronary angiography and percutaneous coronary intervention. Four hundred and forty-five consecutive T2DM patients with significant CAD (≥ 75% stenosis) were included in our analysis. All patients underwent standard clinical examination, laboratory tests and transthoracic echocardiography with measurement of the left ventricular ejection fraction. Severity of CAD at the coronary angiography was evaluated using the Gensini score. Clinical follow-up was completed at 1, 3 and 6 years. During a mean follow-up of 73·3 ± 22·1 months, 109 patients died (24·5%). Significant determinants of an increased risk of death at multivariable analysis were age (p < 0·001), serum creatinine (p = 0·001), peripheral vascular disease (p = 0·002), serum glucose (p = 0·004), serum fibrinogen (p = 0·011) and history of heart failure (HF, p = 0·011). When all the variables were entered as categorical variables, with continuous variables split at their median value, only history of HF, estimated glomerular filtration rate, serum glucose, serum fibrinogen (all p < 0·0001) and beta-blocker therapy at discharge (p = 0·027) were selected. Our study shows a relatively good prognosis of patients with T2DM. Comorbidities, namely HF and renal impairment, are main determinants of survival.


Lumbar spine abnormalities and facet joint angles in asymptomatic elite junior tennis players.
Lumbar spine abnormalities, in particular stress fractures to the pars interarticularis, are common in elite junior tennis players, though the difference in prevalence between males and females remains unclear. Further, facet joint orientation appears to be a possible option for recognizing which players might go on to present with a pars stress fracture. Given the link between pars stress fractures and low back pain in tennis players, it appears logical to explore the link between facet joint angle and pars abnormalities. Thus, the purpose of this study was to describe the prevalence of lumbar spine abnormalities and explore the relationship between facet joint orientation and pars abnormalities in elite adolescent tennis players. Lumbar spine MRI images of 25 elite junior tennis players were obtained and distributed between five radiologists for analysis. Descriptive comparisons and confidence intervals were used to describe the prevalence of the abnormalities. A generalized linear regression model was conducted to investigate the relationship between lumbar pars abnormalities and lumbar facet joint angles. Sixteen (64%) of 25 players were found to have at least one lumbar spine abnormality. Pars abnormalities affected 36% of players while bone marrow edema was found in 24% of players. Disc herniation, disc degeneration, and facet joint degeneration were diagnosed in 20%, 44%, and 24% of players respectively. Lastly, one player (4%) was diagnosed with spondylolisthesis. Females had significantly larger facet joint angles across L3/4 L5/S1 compared to males (p < 0.01). Further, those who had pars abnormalities had larger facet joint angles compared to those who did not (p < 0.001). Disc degeneration, pars abnormalities, including bone marrow edema, and facet joint degeneration were common findings among elite adolescent tennis players. Additionally, this study is the first to discover that pars abnormalities are linked to facet joint angle in elite adolescent tennis players. This finding might assist in identifying tennis players at a greater risk of developing lumbar spine pars abnormalities in the future.


Comparison of costs of staged versus simultaneous lower extremity arterial hybrid procedures.
Hybrid procedures combine endovascular and open surgical techniques. We examined utilization rates and ways of performing them more efficiently. Hybrids were selected using codes for femoral endarterectomy, infrainguinal, or aorto-iliac-femoral bypass and angioplasty from Nationwide Inpatient Sample (NIS) data, then categorized as staged, or performed on the same day. Outcomes included utilization rates, total hospital charges, and length of stay (LOS). Confounders of charges and LOS were identified and excluded from final comparisons. Utilization increased 7% from 2000 to 2004. Univariate associations linked staging to variables included in linear regressions for hospital charges and LOS. Excluding identified confounders from the final subgroup analysis still showed large differences in charges (same-day = $34,206, staged = $60,087) and LOS (same-day = 3 days, staged = 7 days). Utilization of hybrids is increasing. Performing hybrids on the same day, if possible, greatly reduces hospital charges and LOS, emphasizing preadmission planning and simultaneous coordination of both portions.


The nine-year changes of the incidence and characteristics of metabolic syndrome in China: longitudinal comparisons of the two cross-sectional surveys in a newly formed urban community.
To assess the 9-year changes of the incidence and characteristics of metabolic syndrome (MetS) in Chinese community under the background of dramatically changed environment. Two cross-sectional surveys of the general population were carried out in 2005 and 2014 in Dengmin and Hongnan villages of Fengcheng community, a newly formed urban community from rural area 10 years ago. All permanent adult residents aged 18-80 without active malignant tumors and pregnancy were invited to attend the study. They participated in clinical examinations for anthropometric and blood pressure measurements. Fasting blood samples were drawn for analysis of lipids and glucose. Presence of MetS was defined based on the IDF/AHA harmonized criteria. MetS z-score was calculated to evaluate the degree of total metabolic disorder. A total of 1042 subjects in 2005 and 1053 subjects in 2014 were included in the final analysis. The participants were stratified by gender. The incidence of MetS was higher in 2014 than 2005 in both genders (female, 48.28 vs 31.61 %; male, 41.12 vs 26.30 %; p value, both <0.001). Of the five MetS components, the FBG and TG levels were higher in 2014 than 2005 in both gender, however, the SBP and DBP values were even lower in 2014 than 2005. The differences of FBG, blood pressure and lipid levels between 2005 and 2014 still exist after ruling out recognized diabetic, hypertensive and dyslipidemic subjects, individually. In MetS subjects, MetS z-score showed the whole metabolic profile get worse in 2014 than 2005 in both sex (female, 1.97 ± 2.53 vs 1.74 ± 2.29; male, 2.51 ± 2.79 vs 1.01 ± 2.38. both P < 0.001). Using 3 abnormal components as a combination, we found the frequency of different kinds of combination also changed in MetS subjects. In female, the combination of WC + BP + HDL disorder decreased from 29.7 % (2005) to 11.0 % (2014) and WC + FBG + BP disorder became the most popular phenotype (18.8 %) in 2014. The dramatically changed environments have extensive influence on metabolic parameters of local residents. More targeted measures need to be taken to meet the serious challenges of metabolic diseases. Trial registration ChiCTR-ECS-14005052, http://www.chictr.org, Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (SPECT-China).


Impact of ocular graft-versus-host disease on visual quality of life in patients after allogeneic stem cell transplantation: questionnaire study.
To determine the influence of ocular complications on quality of life (QoL) 3 years after allogeneic stem cell transplantation (allo-SCT). All 54 adult patients that underwent and survived allo-SCT in 2006/2007 in our centre received two questionnaires (VFQ-25: visual function questionnaire-25 and OSDI: ocular surface disease index). In addition, the following data were included: gender, age, underlying disease, presence of chronic and/or ocular graft-versus-host disease (GVHD), number of visits to an ophthalmologist, manifestations of dry eye disease, the duration of follow-up and treatment for ocular GVHD. Ocular GVHD developed in 26% (14 of 54) of patients and 71% (10 of 14) received treatment for ocular GVHD. The presence of ocular GVHD correlated with the severity of systemic GVHD (correlation coefficient: 0.52, p = 0.00). The Karnofsky scores were significantly lower in the patients with ocular GVHD compared to the patients with no ocular GVHD (p = 0.001). Karnofsky scores were weakly correlated with the severity of systemic GVHD (correlation coefficient: 0.25, p = 0.03. Three years after the all-SCT, OSDI and VFQ-25 scores were significantly impaired in patients with ocular GVHD [mean: 76.5; range (46.1-100) and mean: 31.1; range (0-72.9)] compared to patients with no ocular GVHD [mean: 89.4; range (45.2-100) and mean: 12.9; range (0-58.3); p = 0.02]. The scores of the VFQ-25 were significantly lower in the domains of general health, ocular pain, social functioning and role difficulties. The long-term vision-related QoL measured by the OSDI and VFQ-25 was impaired in patients with ocular GVHD.


Growth kinetic and fuel quality parameters as selective criterion for screening biodiesel producing cyanobacterial strains.
The efficiency of cyanobacterial strains as biodiesel feedstock varies with the dwelling habitat. Fourteen indigenous heterocystous cyanobacterial strains from rice field ecosystem were screened based on growth kinetic and fuel parameters. The highest biomass productivity was obtained in Nostoc punctiforme MBDU 621 (19.22mg/L/day) followed by Calothrix sp. MBDU 701 (13.43mg/L/day). While lipid productivity and lipid content was highest in Nostoc spongiaeforme MBDU 704 (4.45mg/L/day and 22.5%dwt) followed by Calothrix sp. MBDU 701 (1.54mg/L/day and 10.75%dwt). Among the tested strains, Nostoc spongiaeforme MBDU 704 and Nostoc punctiforme MBDU 621 were selected as promising strains for good quality biodiesel production by Preference Ranking Organization Method for Enrichment Evaluation (PROMETHEE) and Graphical Analysis for Interactive Assistance (GAIA) analysis.


Identification and functional characterization of an endoplasmic reticulum oxidoreductin 1-α gene in Litopenaeus vannamei.
In the current study, full-length sequence of endoplasmic reticulum oxidoreductin 1-α (LvERO1-α) was cloned from Litopenaeus vannamei. Real-time RT-PCR results showed that LvERO1-α was highly expressed in hemocytes, gills, and intestines. White spot syndrome virus (WSSV) challenge was performed, and the expression of LvERO1-α and two other downstream genes of the double-stranded RNA-activated protein kinase-like ER kinase-eIF2α (PERK-α) pathway, namely, homocysteine-induced endoplasmic reticulum protein (LvHERP) and acylamino-acid-releasing enzyme (LvAARE), strongly increased in the hemocytes. Flow cytometry assay results indicated that the apoptosis rate of L. vannamei hemocytes in the LvERO1-α knockdown group was significantly lower than that of the controls. Moreover, shrimps with knockdown expression of LvERO1-α exhibited decreased cumulative mortality upon WSSV infection. Downregulation of L. vannamei immunoglobulin-binding protein (LvBip), which had been proven to induce unfolded protein response (UPR) in L. vannamei, did not only upregulate LvERO1-α, LvHERP, and LvAARE in hemocytes, but also increased their apoptosis rate, as well as the shrimp cumulative mortality. Furthermore, reporter gene assay results showed that the promoter of LvERO1-α was activated by L. vannamei activating transcription factor 4, thereby confirming that LvERO1-α was regulated by the PERK-eIF2α pathway. These results suggested that LvERO1-α plays a critical role in WSSV-induced apoptosis, which likely occurs through the WSSV-activated PERK-eIF2α pathway.


Predicting Infection Related Complications After Endovascular Repair of Infective Native Aortic Aneurysms.
Endovascular aortic repair (EVAR) as surgical treatment for infective native aortic aneurysm (INAA) is associated with superior survival compared with open surgery, but with the risk of infection related complications (IRCs). This study aimed to assess the association between baseline clinical and computed tomography (CT) features and the risk of post-operative IRCs in patients treated with EVAR for INAA. It also sought to develop a model to predict long term IRCs in patients with abdominal INAA treated with EVAR. All initial clinical details and CT examinations of INAAs between 2005 and 2020 at a major referral hospital were reviewed retrospectively. The images were scrutinised according to aneurysm features, as well as peri-aortic and surrounding organ involvement. Data on post-operative IRCs were found in the patient records. Cox regression analysis was used to derive predictors for IRCs and develop a model to predict five year IRCs after EVAR in abdominal INAA. Of 3 780 patients with the diagnosis of aortic aneurysm or aortitis, 98 (3%) patients were treated with EVAR for abdominal INAAs and were thus included. The mean follow up time was 52 months (range 0 ‒ 163). The mean transaxial diameter was 6.5 ± 2.4 cm (range 2.1 ‒14.7). In the enrolled patients, 38 (39%) presented with rupture. The five year IRC rate in abdominal INAAs was 26%. Female sex, renal insufficiency, positive blood culture, aneurysm diameter, and psoas muscle involvement were predictive of five year IRC in abdominal INAA after EVAR. The model had a C-index of 0.76 (95% CI 0.66 - 0.87). Pre-operative clinical and CT features have the potential to predict IRC after endovascular aortic repair in INAA patients. These findings stress the importance of rigorous clinical, laboratory, and radiological follow up in these patients.


erbB in NSCLC as a molecular target: current evidences and future directions.
A number of treatments have been developed for HER1, 2 and 3-driven non-small cell lung cancer (NSCLC), of which the most successful have been the epidermal growth factor receptor-tyrosine kinase inhibitors in HER1-mutant tumours resulting in highly improved progression-free survival. Human epidermal growth factor (HER)2 and 3-driven tumours represent the minority of NSCLC, and effective therapies in these patients still represent an unmet medical need. The encouraging results seen with anti-HER2 and anti-HER3 monoclonal antibodies need to be validated in larger studies, even if the greatest obstacle is represented by the exiguous number of patients bearing deregulated HER2/3 system and abnormalities of signal transduction pathway. Considering NSCLC tumour heterogeneity, which affects response and resistance to treatment, combined multiparametric approaches, such as liquid biopsy together with radiomics, may provide a better understanding of the tumour dynamics and clonal selection during the treatments.


Male gender roles and sexuality: implications for women's AIDS risk and prevention.
The focus of prevention of the heterosexual AIDS epidemic in the U.S. has been on women. The role of men in sexual decision making has not been emphasized in AIDS prevention approaches. As a result, the heterosexual epidemic for women continues unabated because of the lack of attention to the behavior of male sex partners. This article describes a profile of male sex partners and emphasizes gender roles and sexuality. Prevention efforts that focus singly on women have been misguided and have actually served to undermine women by making them responsible for HIV risk reduction. Prevention of AIDS among heterosexuals will require an examination of how traditional gender role socialization runs counter to safer sex practices. Control of the epidemic will require a focus on men as individuals responsible for their own health and the health of women.


An empirical study on the "cathartic effect" of attempted suicide.
A cathartic effect of attempted suicide has been suggested, but few data are available to validate the concept. In this study we report on the relation between presuicidal and postsuicidal mood conditions in a group of 25 hospitalized suicide attempters and 50 control patients who were depressed but not suicidal. A significant decrease in depression was demonstrated to occur in the suicidal patients within a few days of hospitalization. This was not the case in depressed patients without prior suicide attempts. The drop in depression ratings can, therefore, be attributed to the suicide attempt. Possible explanatory factors are discussed. These findings indicate that the diagnosis of a suicide attempt in the absence of depression can only be reliably made on the basis of data pertaining to the presuicidal mood condition.


Lipid Nanoparticle Delivery System for mRNA Encoding B7H3-redirected Bispecific Antibody Displays Potent Antitumor Effects on Malignant Tumors.
The therapeutic use of bispecific T-cell engaging (BiTE) antibodies has shown great potential for treating malignancies. BiTE can simultaneously engage CD3ε on T cells and tumor antigen on cancer cells, thus exerting an effective antitumor effect. Nevertheless, challenges in production, manufacturing, and short serum half-life of BiTE have dampened some of the promise and impeded the pace of BiTE-based therapeutics to combat diseases. Nowadays, in vitro-transcribed mRNA has achieved programmed production, which is more flexible and cost-effective than the traditional method of producing recombinant antibody. Here, the authors have developed a BiTE-based mRNA treatment by encapsulating mRNA encoding B7H3×CD3 BiTE into a novel ionizable lipid nanoparticles (LNPs). The authors have found that LNPs have high transfection efficiency, and the hepatosplenic targeting capability of produce high concentrations of BiTE. Above all, a single intravenous injection of BiTE mRNA-LNPs could achieve high levels of protein expression in vivo and significantly prolonged the half-life of the BiTE, which can elicit robust and durable antitumor efficacy against hematologic malignancies and melanoma. Therefore, their results suggested that the therapeutic strategy based on mRNA expression of B7H3×CD3 BiTE is of potential research value and has promising clinical application prospects.


Radiometric oil well assay for glucokinase in microscopic structures.
Glucokinase (ATP:D-glucose 6-phosphotransferase, EC 22.214.171.124) plays a pivotal role in hepatic glucose metabolism and serves as the glucose sensor in pancreatic islet beta-cells. Biochemical studies of this enzyme are complicated by the cellular heterogeneity of the liver and the pancreas and because the presence of hexokinases (ATP:D-hexose 6-phosphotransferases, EC 188.8.131.52) seriously interferes with currently available analytical procedures. A radiometric assay was designed to deal with these problems. It is based on the liberation of 3H2O from D-[2-3H(N)]glucose 6-phosphate, the product of the glucokinase reaction, using exogenous phosphoglucose isomerase (D-glucose-6-phosphate ketol-isomerase, EC 126.96.36.199). Interference by hexokinases was largely eliminated by using glucose 6-phosphate as inhibitor and the sensitivity of the assay was greatly increased by using small volumes with the oil well procedure. The assay was sufficiently sensitive to detect about 1 pg of glucokinase. It thus allowed the application of quantitative histochemical procedures to the study of intralobular hepatic glucokinase profiles and the pancreatic beta-cell glucose sensor. The quantitative histochemical procedures were sufficiently sensitive and reliable for measuring important kinetic constants of glucokinase (i.e., the Km and the Hill number) in microscopic samples of tissue.


Uveitis following dengue fever.
To report the occurrence of uveitis in patients with prior history of dengue fever. A case series of patients with uveitis, presenting with ocular symptoms 3-5 months after contracting dengue fever during the dengue epidemic without any other attributable cause for uveitis. The dengue fever had subsided without any complication. None of the patients had any ocular complication during the acute dengue infection. They were treated on the lines of uveitis with local steroids, cycloplegic, and ocular hypotensive medications, when required, and oral steroid in case of posterior segment involvement. Patients' follow-up varied from 3-5 months. Six patients with serological evidence of prior dengue fever had presented with uveitis not attributable to any other disease. Seven eyes of six patients were affected. Anterior uveitis without any evidence of posterior segment involvement was present in six eyes of five patients whereas one patient had severe vitritis also. The most common symptom was progressive decrease in vision and only three out of seven eyes had evidence of ciliary congestion. All patients promptly responded to the treatment and visual acuity returned to 6/9 or better in five eyes, while 6/24 and 6/18 in other two eyes due to the presence of cataract. None of these patients had recurrence during the follow-up period. Uveitis in dengue infection is rare and ophthalmologists should be aware of these delayed ophthalmic complications. The prognosis of post-dengue uveitis is good.


Genetic structure of the date palm (Phoenix dactylifera) in the Old World reveals a strong differentiation between eastern and western populations.
Since the publication of this paper, it has become apparent that an error was made in the legend to Fig. 3 and the colours referring to occidental and oriental are the wrong way round. The authors apologise for this error, and a correct version of the legend to Fig. 3 is given below.


Phosphoinositide regulation of voltage-gated sodium channels.
JGP study (Gada et al. 2023. J. Gen. Physiol. https://doi.org/10.1085/jgp.202213255) reveals that the membrane lipid PI(4,5)P2 alters the activity of NaV1.4 channels by modulating their gating behavior.


Rapid Assays for Specific Detection of Fungi of Scopulariopsis and Microascus Genera and Scopulariopsis brevicaulis Species.
Fungi of Scopulariopsis and Microascus genera cause a wide range of infections, with S. brevicaulis being the most prevalent aetiological agent of mould onychomycosis. Proper identification of these pathogens requires sporulating culture, which considerably delays the diagnosis. So far, sequencing of rDNA regions of clinical isolates has produced ambiguous results due to the lack of reference sequences in publicly available databases. Thus, there is a clear need for the development of new molecular methods that would provide simple, rapid and highly specific identification of Scopulariopsis and Microascus species. The objective of this study was to develop simple and fast assays based on PCR and real-time PCR for specific detection of fungi from Scopulariopsis and Microascus genera, and separately, S. brevicaulis species. On the basis of alignment of β-tubulin gene sequences, Microascus/Scopulariopsis-specific primers were designed and S. brevicaulis-specific primers were reevaluated. DNA from cultured fungal isolates, extracted in a two-step procedure, was used in Microascus/Scopulariopsis-specific and S. brevicaulis-specific PCR and real-time PCR followed by electrophoresis or melting temperature analysis, respectively. The specificity of the assays was confirmed, as positive results were obtained only for Scopulariopsis spp. and Microascus spp. isolates tested in Microascus/Scopulariopsis-specific assay, and only for S. brevicaulis and S. koningii (syn. S. brevicaulis) isolates in a S. brevicaulis-specific assay, respectively, and no positive results were obtained neither for other moulds, dermatophytes, yeast-like fungi, nor for human DNA. The developed assays enable fast and unambiguous identification of Microascus spp. and Scopulariopsis spp. pathogens.


A, B and H group specific substances in human vitreous humor.
The presence of A, B and H group specific substances in vitreous humor taken from 105 human corpses was determined. Good agreement was obtained between these group substances and the ABO blood group. The relationship with the secretor type is discussed.