Synthetic molecular evolution of antimicrobial peptides.
As we learn more about how peptide structure and activity are related, we anticipate that antimicrobial peptides will be engineered to have strong potency and distinct functions and that synthetic peptides will have new biomedical applications, such as treatments for emerging infectious diseases. As a result of the enormous number of possible amino acid sequences and the low-throughput nature of antimicrobial peptide assays, computational tools for peptide design and optimization are needed for direct experimentation toward obtaining functional sequences. Recent developments in computational tools have improved peptide design, saving labor, reagents, costs, and time. At the same time, improvements in peptide synthesis and experimental platforms continue to reduce the cost and increase the throughput of peptide-drug screening. In this review, we discuss the current methods of peptide design and engineering, including in silico methods and peptide synthesis and screening, and highlight areas of potential improvement.


Large-scale production of a disulfide-stabilized constitutively active mutant opsin.
Previous studies of constitutively activated mutants of opsin in the absence of chromophore were carried out in crude cell membranes because such mutants could not be recovered in a detergent-solubilized form in the active state. We employed a strategy in which a stabilizing disulfide bond allowed for successful purification of a constitutively activated mutant opsin, N2C/E113Q/M257Y/D282C, solubilized in nonionic detergent from mammalian cell culture. The purified mutant opsin is able to activate transducin to a higher degree than opsin and may prove useful for future structural studies of the active state of GPCRs.


The interactions of factors X and IX with phospholipid.
The interactions of human factors X and IX with phospholipid were studied with an ELISA system. In the presence of calcium ions, factor X bound to phosphatidylserine with an affinity of 1.56 x 10(10) M-1 and to phosphatidylcholine with an affinity of 5.6 x 10(9) M-1. In the presence of calcium ions, factor IX bound to phosphatidylserine with an affinity of 8.4 x 10(8) M-1 and no binding to phosphatidylcholine was observed. No competition of factors X and IX for phosphatidylserine binding sites was observed.


Isolation of human immunodeficiency virus type 1 from semen and vaginal fluids.
Semen and vaginal fluids transmit HIV infection. The virus is present as cell-free particles and as infected cells. Isolation of infectious virus from both genital tract fluids poses unique problems. Vaginal fluids are heavily contaminated with normal bacterial flora, and seminal plasma is cytotoxic to peripheral blood mononuclear cells. Adaptations of routine laboratory procedures have been developed to largely overcome these problems, allowing the culture and characterization of genital-tract HIV.


Isobaric Labeling-Based LC-MS/MS Strategy for Comprehensive Profiling of Human Pancreatic Tissue Proteome.
The pancreas is an organ with both endocrine and exocrine functions, and various pathologies, such as pancreatic cancer and diabetes are associated with this organ. Owing to the limited pancreatic biopsy samples available for research, it is critical to make the best use of cadaveric pancreatic tissue for biomarker studies and mechanistic understanding of pancreas-related pathologies. Discovery-phase quantitative proteomics has attracted a lot of attention for its capabilities in large-scale protein identification and accurate protein quantification. Here, we describe a workflow using isobaric labeling (tandem mass tag or TMT) based quantitative proteomics to confidently identify and quantify human pancreatic tissue proteome, including sample preparation, isobaric tag labeling, peptide level fractionation, LC-MS/MS, database search, and statistical analysis.


Cyclic AMP receptor protein and TyrR are required for acid pH and anaerobic induction of hyaB and aniC in Salmonella typhimurium.
Two acid-inducible genes, aniC and aciK, that require anaerobiosis and tyrosine for expression were identified as orf326a encoding a potential amino acid/polyamine antiporter and hyaB encoding hydrogenase I, respectively. Cyclic AMP (cAMP) receptor protein, cAMP, and TyrR, regulator of aromatic amino acid metabolism, were strong positive regulators of both genes.


Imaging findings of paediatric oncology patients presenting with acute neurological symptoms.
Paediatric oncology patients are prone to central nervous system (CNS) complications due to multiple factors including disorders of the blood cell counts (which include neutropenia, thrombocytopenia or hyperleukocytosis), immunosuppression, neurotoxicity of the treatment, CNS dysfunction due to failure of other organ systems, disease progression of the primary malignancy or metastases. Imaging plays an important role in the management of paediatric oncology patients presenting with acute neurological symptoms. This pictorial review is from our institutional experience on imaging children who are under the care of the Child Cancer Centre. The review consists of a spectrum of neurological complications in paediatric oncology patients. The complications can be classified as (1) cerebrovascular complications, (2) treatment-elated complications, (3) opportunistic infections and (4) tumoural involvement of the CNS. Computed tomography (CT) is the initial choice of investigation, which is easily available and helps to exclude major intracranial abnormality such as haemorrhage. If the CT is negative, magnetic resonance imaging (MRI) should be performed, which is more sensitive for detection of CNS lesions.


Preparation and evaluation of inclusion complexes of commercial sunscreens in cyclodextrins and montmorillonites: performance and substantivity studies.
Herein we describe inclusion complexes of commercial sunscreens in cyclodextrins and montmorillonites to generate new sunscreen derivatives with optimized functional properties such as water resistance and skin adherence. Four cyclodextrins (alpha-, beta-, and gamma-cyclodextrin, and beta-dimethyl cyclodextrin) and two montmorillonites (sodium and alkylammonium) were investigated for encapsulating some commercial sunscreens. Our results reveal a good yield and inclusion products with functional properties obtained by using kneading technique on Eusolex 2292 and Eusolex 6007 in beta-cyclodextrin and solubilization method on Eusolex 6007 and NeoHeliopan MA in montmorillonite. In addition, molecular modeling studies indicated flexibility as important for the intercalation of the host molecule.


Brachioplasty.
The upper arm is a difficult area to manage after massive weight loss. The goal of the authors' new technique is to avoid complications in massive weight loss cases and simple cases because of aging. After analysis of the excess skin, the authors explain their markings. The main innovation is to preserve all the lymphatic vessels, both the deep and superficial ones, thanks to liposuction and very superficial resection. This eliminates effusions and maintains good vascularization of the wound edges. The suturing technique used to close the wound is very important for minimizing the risks of widening the scar.


Association of plasma levels of F11 receptor/junctional adhesion molecule-A (F11R/JAM-A) with human atherosclerosis.
The purpose of this study was to determine the association of the F11 receptor (F11R) with human vascular disease. A molecule identified as critical for platelet adhesion to a cytokine-inflamed endothelial surface in vitro is F11R. The F11R is known to be expressed in platelets and endothelium and reported recently to be overexpressed in atherosclerotic plaques. A novel enzyme-linked immunosorbent assay was developed for the measurement of soluble F11R in human plasma. The F11R levels, along with a number of other biomarkers, were measured in 389 male patients with known or suspected coronary artery disease (CAD) undergoing coronary angiography at a Veterans Administration Medical Center. Patients with normal or nonobstructive disease (CAD angiographic score of 0), mild-to-moderate disease (score of 1 to 3), and severe disease (score of 4 to 6) had median F11R plasma levels of 38.6 pg/ml (mean 260 +/- 509.6 pg/ml), 45.2 pg/ml (mean 395.3 +/- 752.7 pg/ml), and 105.8 pg/ml (mean 629 +/- 831.7 pg/ml), respectively (p = 0.03). By multivariate analysis, the variables independently associated with CAD score were age, hyperlipidemia, chronic renal insufficiency, left ventricular function, and plasma F11R levels. The F11R was the only biomarker that was independently associated with CAD score. Consistent with the previously reported effects of tumor necrosis factor (TNF)-alpha on F11R expression in cultured endothelial cells, F11R levels correlated strongly with plasma TNF-alpha levels (r = 0.84; p < 0.0001). Plasma F11R is independently associated with the presence and severity of angiographically defined CAD. By virtue of its strong correlation to plasma TNF-alpha, F11R may be an important mediator of the effects of inflammation on the vessel wall. Strategies that block F11R may represent a novel approach to the treatment of human atherosclerosis.


Toxic boost: Acute, reversible neurotoxicity after ingestion of methylcyclopentadienyl manganese tricarbonyl (MMT) mistaken for an energy drink.
Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organometallic compound used as a gasoline additive for its antiknock properties. Human ingestion of MMT has not previously been reported. We present the case of a 54-year-old man who developed seizures and altered mental status after drinking 12 oz. of MMT-containing NOS Octane Booster Racing Formula. Due to label similarities, he mistook this for the NOS High Performance energy drink. The patient was intubated due to persistent seizures despite benzodiazepine treatment and admitted to the intensive care unit. He had two further seizures while intubated, but he was successfully extubated on the 4th day post-ingestion. He was confused and ataxic following extubation, but one day later his symptoms resolved and he was discharged without further incident. This case highlights the importance of responsible labeling of consumables. It is important for clinicians and poison centers to report any such instances to the United States Food and Drug Administration.


Role of sequence variations in the human ether-a-go-go-related gene (HERG, KCNH2) in the Brugada syndrome.
Brugada syndrome (BrS) is an inherited electrical disorder associated with a high incidence of sudden death. In a minority of patients, it has been linked to mutations in SCN5A, the gene encoding the pore-forming alpha-subunit of the cardiac Na(+) channel. Other causally related genes still await identification. We evaluated the role of HERG (KCNH2), which encodes the alpha-subunit of the rapid delayed rectifier K(+) channel (I(Kr)), in BrS. In two unrelated SCN5A mutation-negative patients, different amino acid changes in the C-terminal domain of the HERG channel (G873S and N985S) were identified. Voltage-clamp experiments on transfected HEK-293 cells show that these changes increase I(Kr) density and cause a negative shift of voltage-dependent inactivation, resulting in increased rectification. Action potential (AP) clamp experiments reveal increased transient HERG peak currents (I(peak)) during phase-0 and phase-1 of the ventricular AP, particularly at short cycle length. Computer simulations demonstrate that the increased I(peak) enhances the susceptibility to loss of the AP-dome typically in right ventricular subepicardial myocytes, thereby contributing to the BrS phenotype. Our study reveals a modulatory role of I(Kr) in BrS. These findings may provide better understanding of BrS and have implications for diagnosis and therapy.


Different climbing fibres innervate separate dendritic regions of the same Purkinje cell in hypogranular cerebellum.
Electrophysiological experiments have shown that in hypogranular cerebella the Purkinje cells are innervated by several climbing fibres. The aim of this paper is to provide morphological evidence for this multiple innervation and to describe the topographical distribution of the different climbing fibres onto the somadendritic region of the Purkinje cell. Experiments have been performed in hypogranular adult Wistar rats lesioned during the first postnatal week by methylazoxymethanol (MAM) or by X-irradiation. Purkinje cells were labelled by an anti-calbindin antibody, whereas climbing fibres were visualised by means of Phaseolus vulgaris leucoagglutinin. Purkinje cells showed variable degrees of abnormality and displacement. Climbing fibres made contact with the dendrites of all kinds of Purkinje cells, including those ectopically positioned whose dendrites branched in the white matter. This shows that Purkinje cells can develop dendritic branching in the absence of granule cells and maintain the capability of interacting with their proper afferents, even when they are severely affected and displaced. In four Purkinje cells we have been able to follow the course of two climbing fibre terminal arbourisations. Almost no terminal branches were present around the Purkinje cell soma, and the whole arbour covered the proximal two-thirds of the Purkinje cell dendritic tree. These arbourisations, after an initial common course along the primary dendrite, distributed to separate dendritic regions. The observation of a single labelled climbing fibre covering a limited region of the dendritic tree was more common. As this finding is never observed in control material, it is concluded that the remaining region is covered by another unlabelled climbing fibre belonging to a different inferior olive neurone. These results represent a morphological demonstration of multiple climbing fibre innervation of the adult Purkinje cell. The maintenance of polyinnervation in the adult, which is consequent to the loss of granule cells, is not associated with a defect in the peridendritic translocation of the olivary arbour. In addition, the strict segregation of the different climbing fibres to distinct territories of the Purkinje cell dendritic tree suggests that each terminal arbourisation acts as a functionally independent unit and prevents other competitors from invading its own target domain.


Is cribriform pattern in prostate biopsy a risk factor for metastatic disease on 68Ga-PSMA-11 PET/CT?
Cribriform growth pattern (CP) in prostate cancer (PCa) has been associated with different unfavourable oncological outcomes. This study addresses if CP in prostate biopsies is an independent risk factor for metastatic disease on PSMA PET/CT. Treatment-naive patients with ISUP GG ≥ 2 staged with 68Ga-PSMA-11 PET/CT diagnosed from 2020 to 2021 were retrospectively enrolled. To test if CP in biopsies was an independent risk factor for metastatic disease on 68Ga-PSMA PET/CT, regression analyses were performed. Secondary analyses were performed in different subgroups. A total of 401 patients were included. CP was reported in 252 (63%) patients. CP in biopsies was not an independent risk factor for metastatic disease on the 68Ga-PSMA PET/CT (p = 0.14). ISUP grade group (GG) 4 (p = 0.006), GG 5 (p = 0.003), higher PSA level groups per 10 ng/ml until > 50 (p-value between 0.02 and > 0.001) and clinical EPE (p > 0.001) were all independent risk factors. In the subgroups with GG 2 (n = 99), GG 3 (n = 110), intermediate-risk group (n = 129) or the high-risk group (n = 272), CP in biopsies was also not an independent risk factor for metastatic disease on 68Ga-PSMA PET/CT. If the EAU guideline recommendation for performing metastatic screening was applied as threshold for PSMA PET/CT imaging, in 9(2%) patients, metastatic disease was missed, and 18% fewer PSMA PET/CT would have been performed. This retrospective study found that CP in biopsies was not an independent risk factor for metastatic disease on 68Ga-PSMA PET/CT.


Surgical correction of caruncular distortion after medial rectus resection.
Strabismus surgery can lead to successful eye alignment but may cause scarring and distortion of conjunctiva and adjacent structures in some cases. We report two patients who developed epiphora when the lacrimal caruncles became distorted after strabismus surgery. Both cases followed successful medial rectus muscle resections for exotropia. A simple excision of the caruncles improved the epiphora and produced a satisfactory appearance.


Solvent effects on the cooperative order-disorder transition of aqueous solutions of schizophyllan, a triple-helical polysaccharide.
A triple helical polysaccharide schizophyllan in aqueous solution exhibited a highly cooperative transition between ordered and disordered states associated with the conformation of its side chains and nearby water molecules. The transition was followed by optical rotation and calorimetry using water containing additives such as NaOH and DMSO as solvents. The ordered state was stabilized or destabilized depending on the kind and amount of the additive employed; in particular, the addition of DMSO had a remarkable stabilizing effect. This effect was analyzed by means of a statistical mechanical theory of linear cooperative transitions, where DMSO was assumed to interact favorably with the ordered side chains. A small amount of NaOH in a solvent mixture stabilized the ordered state and made the transition curve very gradual. No molecular mechanism was elucidated to account for the role of NaOH.


[Elastosis Perforans Serpiginosa and Wilson Disease: A Rare but Predictable Consequence of Long-term Therapy with D-Penicillamine].
Elastosis perfurans serpiginosa is a rare perforating dermatosis found primarily in adolescents and young adults, characterized by transepidermal elimination of abnormal elastic fibers. The only drug known capable of inducing elastosis perfurans serpiginosa is D-penicillamine. We report the case of a 52 year-old woman with keratotic papules arranged in an annular pattern with central clearing and centrifugal growth, located in the anterior cervical region. The patient was chronically treated with D-penicillamine for Wilson disease. Lesion biopsy showed transepidermal elimination of thickened, eosinophilic, branched, sawtooth-like elastic fibers. The clinical and pathological findings were consistent with elastosis perfurans serpiginosa secondary to D-penicillamine. It is estimated that elastosis perfurans serpiginosa occurs in 1% of patients treated with D-penicillamine. By blocking directly or indirectly the desmosine cross-links between elastin molecules, D-penicillamine leads to the synthesis of abnormal dermal and extracutaneous elastic fibers. Elastosis perfurans serpiginosa may be the first manifestation of a multisystemic degenerative process of elastic connective tissue.


Lornoxicam attenuates the haemodynamic responses to laryngoscopy and tracheal intubation in the elderly.
Lornoxicam is a novel non-steroidal anti-inflammatory drug with marked analgesic property. It has been shown to have analgesic potency similar to morphine and meperidine. Laryngoscopy and tracheal intubation provoke major haemodynamic responses. Minimizing perioperative adverse events in elderly patients is of utmost importance. The aim of this study was to demonstrate the effect of preoperative administration of Lornoxicam on haemodynamic changes during laryngoscopy and tracheal intubation in the elderly. Fifty patients aged between 65 and 75 yr were randomly recruited to this randomized, double-blind, placebo-controlled study. They were divided into two groups to receive either Lornoxicam 8 mg or placebo half an hour before surgery. Systolic and diastolic blood pressure, mean arterial pressure, and heart rate were recorded before and after administration of the intravenous anaesthetic, also at 1, 3, 5 and 10 min after tracheal intubation. In the control group, significant increases in the haemodynamic parameters were observed during the first 10 min following tracheal intubation (P < 0.05). Preoperative administration of Lornoxicam attenuates the haemodynamic response to laryngoscopy and tracheal intubation in the elderly.


Distribution characteristics of ethosuximide in discrete areas of rat brain.
The distribution properties of ethosuximide in four regions of the rat brain--cortex, midbrain, cerebellum, and pons-medulla--were investigated following chronic intraperitoneal administration of the drug (every 12 hr for 108 hr) at four dose levels (20, 40, 60, and 80 mg/kg). A gas-liquid chromatographic procedure was developed to quantitate ethosuximide levels in these tissues and plasma. The mean tissue/plasma ratios were 0.917, 0.942, 0.902, and 0.903 for cortex, midbrain, cerebellum, and pons-medulla, respectively. The distribution ratio for midbrain was significantly greater than that observed for cerebellum. For each brain region, the distribution ratio was independent of dose (20 to 80 mg/kg) and plasma concentration (8 to 135 microgram/ml).


Novel imidazole-functionalized cyclen cationic lipids: synthesis and application as non-viral gene vectors.
A series of novel 1,4,7,10-tetraazacyclododecanes (cyclen)-based cationic lipids bearing histidine imidazole group 10a-10e were synthesized. These amphiphilic molecules have different hydrophobic tails (long chain, cholesterol or α-tocopherol) and various type of linking groups (ether, carbamate or ester). These molecules were used as non-viral gene delivery vectors, and their structure-activity relationships were investigated. As expected, the imidazole group could largely improve the buffering capabilities comparing to cyclen. The liposomes formed from 10 and dioleoylphosphatidyl ethanolamine (DOPE) could bind and condense plasmid DNA into nanoparticles with proper size and zeta-potentials. Comparing with Lipofectamine 2000, the formed lipoplexes gave lower transfected cells proportion, but higher fluorescence intensity, indicating their good intracellular delivering ability. Furthermore, results indicate that transfection efficiency of the cationic lipids is influenced by not only the hydrophobic tails but also the linking group. The cyclen-based cationic lipid with α-tocopherol hydrophobic tail and an ester linkage could give the highest transfection efficiency in the presence of serum.


Evaluation of olfactory function in children with allergic rhinitis and nonallergic rhinitis.
Allergic rhinitis (AR) occurs when the symptoms of rhinitis arise as a result of allergen-induced nasal mucosal inflammation. In the presence of rhinitis symptoms without infection or an allergic reaction in the nose, non-allergic rhinitis (NAR) is considered. Adults with these diseases have increased frequency of olfactory dysfunction. The aim of the present study is to assess olfactory function in children with AR and NAR. A total of 77 children (aged six to 18 years) with AR and NAR were included in the study. The control group consisted of 45 healthy children. Sniffin' Sticks test was applied to both groups. The association between odor scores and demographic, clinical, and laboratory results was investigated. Forty two patients had allergic rhinitis. No significant difference was observed between patients with rhinitis and healthy controls with respect to odor scores. No association was observed between odor scores and the severity of rhinitis and the laboratory results of the patient groups. Odor identification and total odor scores of the patients with rhinitis lasting for longer than three years were significantly lower than those in the patient group with rhinitis lasting for one to three years. In the AR and control groups, the odor scores were found to increase with age. When compared with healthy children, children with allergic rhinitis and non-allergic rhinitis were not found to have reduced olfactory function. The duration of rhinitis may be associated with the olfactory dysfunction in children with rhinitis.


[Physical therapy possibilities in the treatment of collagen diseases].
We report about the rank of physiotherapy in the treatment of connective tissue diseases with special emphasize on scleroderma. Based upon therapeutic aim physiotherapeutic approaches for lupus erythematosus, dermatomyositis, and scleroderma are pointed out.


Elevated myoplasmic calcium in exercise-induced equine rhabdomyolysis.
Exertional rhabdomyolysis is a myopathy of unknown pathophysiology. We measured intracellular resting calcium concentration ([Ca2+]i) by means of Ca(2+)-selective microelectrodes in intercostal muscle fibers from horses suffering from rhabdomyolysis, and from horses with no evidence of neuromuscular disorder. [Ca2+]i was several-fold higher in muscle fibers from horses suffering from rhabdomyolysis when compared to controls. Treatment of rhabdomyolytic horses with dantrolene, an agent that prevents Ca2+ release from the sarcoplasmic reticulum, reduced [Ca2+]i toward control values, and accelerated the recovery from this myopathy. These results indicate that an acute episode of rhabdomyolysis is associated with elevation in [Ca2+]i in skeletal muscles, and that dantrolene might be of benefit in treating this disease.


The Rhythm ID Going Head to Head Trial (RIGHT): design of a randomized trial comparing competitive rhythm discrimination algorithms in implantable cardioverter defibrillators.
The implantable cardioverter defibrillator (ICD) has become primary therapy for the prevention of sudden death. One of the major morbidities of ICD use remains inappropriate therapy for supraventricular arrhythmias (SVA). Detection enhancements have increased therapy specificity, but their impact on inappropriate therapy is not well studied. Moreover, ICD manufacturers have developed unique algorithms to meet this goal, with no previous clinical direct comparisons. RIGHT is a randomized, prospective study that will assess the differential efficacy of ICDs from two different manufacturers. It is the first trial to compare directly competitive ICD rhythm discrimination algorithms on a large scale. The primary objective of this study is to assess arrhythmia discrimination in Guidant versus Medtronic ICDs by comparing the time to first inappropriate therapy after the predischarge visit. The study will enroll approximately 2,000 patients in 100 centers. Patients will be randomized to Guidant or Medtronic using a permuted block design, stratified by center and by single/dual chamber device types. Patients will receive a commercially available Guidant VITALITY 2 family ICD with Rhythm ID or a Medtronic ICD using the Enhanced PR Logic or Wavelet discrimination algorithms, and will be followed according to the schedule shown until a common closing date with a minimum follow-up of 12 months. All events will be reviewed by an independent committee to determine the appropriateness of rhythm classification and therapy delivery. RIGHT is the first randomized, large scale, head-to-head comparison of ICD discrimination algorithms.


[Effectiveness of a topical medical treatment following diathermic coagulation: controlled clinical study].
A controlled clinical study has been conducted on the efficacy of a topic therapy. Kanamicine sulphate daily for 6 days and altered to polidesossiribonucleotide for the following 24 days were given after cervical cauterization for ectropion with or without AnTZ. Treated patients were 148 and untreated ones were 155. Subjective and objective parameters were evaluated. Among the former only bloody discharge (more frequent among the treated patients) and ill-smelling discharge (more frequent among the untreated patients) showed significant differences. Colposcopy instead showed better (or faster) healing of the treated group, with 83.6% vs 62% iodine dark cervices at Schiller test and 87.9% vs 59.7% SCJ at the external os or inside (P less than 0.01). Also disepitelized areas or areas with frail epithelium were less common among the treated patients.


Probiotics-Derived Peptides and Their Immunomodulatory Molecules Can Play a Preventive Role Against Viral Diseases Including COVID-19.
As of recent, the pandemic episode of COVID-19, a severe acute respiratory syndrome brought about by a novel coronavirus (SARS-CoV-2) expanding the pace of mortality, has affected the disease rate profoundly. Invulnerability is the fundamental choice to prevent the ruining event of COVID-19, as the drugs and antibodies are in the phase of preliminary clinical trials. Within this brief period, a few strains of SARS-CoV-2 have been recognized by the vaccine manufacturers, which could be an incorrect guess about the strain that will end up spreading. Since the circulating SARS-CoV-2 strains continue to mutate, immunizations, if at all works, might be for a restricted time. We have not put sufficient time in research to understand the immune responses that correlate with protection as this could help refine vaccines. Here, we have summed up the adequacy of the immunomodulatory component of probiotics for the prevention against viral infections. Furthermore, an in silico data have been provided in support of the "probiotics-derived lipopeptides" role in inactivating spike (S) glycoprotein of SARS-CoV-2 and its host receptor molecule, ACE2. Among well characterized lipopeptides derived from different probiotic strains, subtilisin (Bacillus amyloliquefaciens), curvacin A (Lactobacillus curvatus), sakacin P (Lactobacillus sakei), lactococcin Gb (Lactococcus lactis) was utilized in this study to demonstrate a higher binding proclivity to S-protein of SARS-CoV-2 and human ACE2. The outcome revealed noteworthy capabilities of the lipopeptides, due to their amphiphilic nature, to bind spike protein and receptor molecule, which may act to competitively inhibit the mandatory interaction of SARS-CoV-2 with the host epithelial cell expressing ACE2 for its entry into the cell for reproduction. In the current situation, probiotic treatment alongside chemotherapy may assist in bringing about substantial improvement of the health of COVID-19 patients. At the same time, probiotics may aid towards building up the immune defenses in people to evade COVID-19.


The recognition of facial expressions: an investigation of the influence of age and cognition.
The present study aimed to investigate changes in facial expression recognition across the lifespan, as well as to determine the influence of fluid intelligence, processing speed, and memory on this ability. Peak performance in the ability to identify facial affect was found to occur in middle-age, with the children and older adults performing the poorest. Specifically, older adults were impaired in their ability to identify fear, sadness, and happiness, but had preserved recognition of anger, disgust, and surprise. Analyses investigating the influence of cognition on emotion recognition demonstrated that cognitive abilities contribute to performance, especially for participants over age 45. However, the cognitive functions did not fully account for the older adults' impairments on expression recognition. Overall, the age-related deficits in facial expression recognition have implications for older adults' use of non-verbal communicative information.


Increased Severity and Spread of Mycobacterium ulcerans, Southeastern Australia.
Reported cases of Mycobacterium ulcerans disease (Buruli ulcer) have been increasing in southeastern Australia and spreading into new geographic areas. We analyzed 426 cases of M. ulcerans disease during January 1998-May 2017 in the established disease-endemic region of the Bellarine Peninsula and the emerging endemic region of the Mornington Peninsula. A total of 20.4% of cases-patients had severe disease. Over time, there has been an increase in the number of cases managed per year and the proportion associated with severe disease. Risk factors associated with severe disease included age, time period (range of years of diagnosis), and location of lesions over a joint. We highlight the changing epidemiology and pathogenicity of M. ulcerans disease in Australia. Further research, including genomic studies of emergent strains with increased pathogenicity, are urgently needed to improve the understanding of disease to facilitate implementation of effective public health measures to halt its spread.


Measuring Italian citizens' engagement in the first wave of the COVID-19 pandemic containment measures: A cross-sectional study.
In January 2020, the coronavirus disease 2019 (COVID-19) started to spread in Italy. The Italian government adopted urgent measures to slow its spread. Enforcing compliance with such measures is crucial in order to enhance their effectiveness. Engaging citizens in the COVID-19 preventive process is urgent today both in Italy and around the world. However, to the best of our knowledge, no previous studies have investigated the role of health engagement in predicting citizens' compliance with health emergency containment measures. An online survey was administered between February 28 and March 4, 2020 on a representative sample of 1000 Italians. The questionnaire included a measure of health engagement (Patient Health Engagement Scale), a 5-item Likert scale ranging from 1 to 7, resulting in 4 positions that describe the psychological readiness to be active in one's own health management, and a series of ad hoc items intended to measure citizens' perceived susceptibility and severity of the disease, orientation towards health management, trust in institutional bodies, health habits and food consumption. To investigate the relationship between health engagement and these variables, ANOVA analysis, logistic regression and contingency tables with Pearson's chi-squared analysis have been carried out. Less engaged people show higher levels of perceived susceptibility to the virus and severity of the disease; they are less trustful of scientific and healthcare authorities, they feel less self-effective in managing their own health-both in normal conditions and under stress-and are less prone to cooperate with healthcare professionals. Low levels of health engagement also are associated with a change in the usual purchase behavior. The Patient Health Engagement model (PHE) provides a useful framework for understanding how people will respond to health threats such as pandemics. Therefore, intervention studies should focus on raising their levels of engagement to increase the effectiveness of educational initiatives intended to promote preventive behaviors.


Solution structure of the DNA complexes with an alkyl-linked bis(benzimidazole) compound, 1,4-bis[5-(4-methyl-1-piperazinyl)-2-benzimidazolyl]butane.
Solution structures of the 1:1 complexes of an alkyl-linked bis(benzimidazole) compound (4; Figure 1(a)) with the self-complementary DNA duplexes, d(CGCGAATTCGCG)2 and d(CGCAAATTTGCG)2, have been studied by 1H NMR spectroscopy and molecular mechanics calculations. The intermolecular NOE data and the energy-minimized geometries of the 1:1 complexes indicate that 4 binds in the minor groove of the 5'-GAATTCG and 5'-CAAATTT regions of the DNA duplexes.


[Variable pressure changes (+/-) in the anterior ischemia syndrome--the elements of a reserved prognosis in the surgery of retinal detachment].
The authors show that the variations of intraocular hyper- and hypotension stand for a reserved prognosis in the evolution of the operated retina detachment. Likewise, they consider that the repeated operations in the retina detachment may lead to the syndrome of anterior ischemia, unfavourable to the visual function.


Ecological risk identification and assessment of land remediation project based on GIS technology.
A land remediation project involves the removal of potentially toxic chemicals from a polluted site. Lands abandoned by industry are often contaminated with heavy metals like mercury, lead, chemicals, arsenic, and other toxins like dichlorodiphenyltrichloroethane biphenyls from electronic devices, and volatile organic chemicals (VOCs) from lubricants and chemicals. Risk assessment in environmental settings requires modernized systematic methodologies due to the complexity of today's environmental problems. When people eat, drink, or work in polluted environments, they put their health at risk and may even get cancer. Integrating geospatial information systems (GIS) with pollutant dispersion models makes environmental risk assessment and early warning possible. This research thus presents a GIS-based ecological risk identification and assessment model (GIS-ERIAM) for assessing risk for efficient land rehabilitation. Environmental cleanup sites' catalog information is the source of these details. With satellite imagery, GIS makes it simple to keep an eye on the environment and track the abundance of different types of plants and animals The ecological risk assessment (ERA) model can support recognition and prioritize risk management. By integrating direct and indirect environment interactions, the risk conditions of the whole ecology and its elements have been quantified and demonstrated in the study. The numerical outcomes illustrate that the recommended GIS-ERIAM model improves the performance by 98.9%, risk level prediction by 97.3%, risk classification by 96.4%, and detection of soil degradation ratio of 95.6% compared to other existing methods.


The many faces of REST oversee epigenetic programming of neuronal genes.
Nervous system development relies on a complex signaling network to engineer the orderly transitions that lead to the acquisition of a neural cell fate. Progression from the non-neuronal pluripotent stem cell to a restricted neural lineage is characterized by distinct patterns of gene expression, particularly the restriction of neuronal gene expression to neurons. Concurrently, cells outside the nervous system acquire and maintain a non-neuronal fate that permanently excludes expression of neuronal genes. Studies of the transcriptional repressor REST, which regulates a large network of neuronal genes, provide a paradigm for elucidating the link between epigenetic mechanisms and neurogenesis. REST orchestrates a set of epigenetic modifications that are distinct between non-neuronal cells that give rise to neurons and those that are destined to remain as nervous system outsiders.


Central bank responses to COVID-19.
Central bank responses to COVID-19 have been extraordinary in speed, in size and in scope. Much easier monetary policy, massive liquidity provision, and targeted credit support to the real economy all played a role in stabilizing financial conditions and credit. On net, there is preliminary evidence that central bank actions have been a positive-for access to credit and for the real economy-during very trying times. But the first six months have made clear that central bank policy can only indirectly address the core economic policy challenges of the crisis, whose trajectory remains highly uncertain. The risks to the economy and financial system remain very large, and key policy questions-on the degree of fiscal policy support to the real economy, about the limits of central bank risk taking and monetization of debt, and about the wisdom of heavy reliance on central bank policies given their impact on leverage and debt levels-remain just that.


Submental flap practice patterns and perceived outcomes: A survey of 212 AHNS surgeons.
To describe American Head and Neck Society (AHNS) surgeon submental flap (SMF) practice patterns and to evaluate variables associated with SMF complications. The design is a cross-sectional study. An online survey was distributed to 782 AHNS surgeons between 11/11/16 and 12/31/16. Surgeon demographics, training, practice patterns and techniques were characterized and evaluated for associations with frequency of SMF complications. Among 212 AHNS surgeons, 108 (50.9%) reported performing SMFs, of whom 86 provided complete responses. Most surgeons who performed the SMF routinely reconstructed oral cavity defects with the flap (86.1%, n = 74). Thirty-seven surgeons (43.0%) experienced "very few" complications with the SMF. Surgeons who practiced in the United States versus internationally (p = 0.003), performed more total career SMFs (p = 0.02), and routinely reconstructed parotid and oropharyngeal defects (p = 0.04 and p < 0.001) with SMFs were more frequently perceived to have "very few" complications. SMF surgeons reported more perceived complications with the SMF compared to pectoralis major (p = 0.001) and radial forearm free flaps (p = 0.01). However, similar perceived complications were reported between all three flaps when surgeons performed >30 SMF. Among 94 surgeons not performing SMFs, 71.3% had interest in a SMF training course. Practice patterns of surgeons performing SMFs are diverse, although most use the flap for oral cavity reconstruction. While 43% of surgeons performing the SMF reported "very few" complications, overall complication rates with the SMF were higher compared to other flaps, potentially due to limited experience with the SMF. Increased training opportunities in SMF harvest and inset are indicated.


A comparison of molecular properties of hepatic triglyceride lipase and lipoprotein lipase from human post-heparin plasma.
Hepatic triglyceride lipase was isolated from human post-heparin plasma by the method of Ehnholm et al. using modifications which increased the specific activity 12-fold to approximately 3,000 mumol of free fatty acid/h/mg of protein. Lipoprotein lipase with similar specific activity was prepared from the same plasma samples using heparin and concanavalin A affinity chromatography. The molecular weight of hepatic triglyceride lipase (69,000) was slightly greater than that of lipoprotein lipase (67,000) as determined by polyacrylamide electrophoresis in sodium dodecyl sulfate-containing buffers. These proteins had identical amino acid compositions, terminal amino acid residues, and tryptic peptide maps. However, the differences previously described regarding optima of pH and ionic strength and the requirement for apolipoprotein CII (only for lipoprotein lipase) were maintained in the highly purified state. It was found that both proteins contain approximately 8% carbohydrate. Antisera prepared in goats selectively precipitated each activity. Other antisera prepared in chickens reacted with both enzymes, suggesting a common antigenic determinant.


Growth monitoring: testing the new guidelines.
To assess the impact of recent guidelines from the UK joint working party of child health surveillance recommending that all children be measured at age 5 and again between 7 and 9 years of age to determine how many normal school age children are likely to be referred for specialist assessment. The longitudinal data of 486 children measured by school nurses in a community setting were examined and compared with measurements made in a research setting by a single, skilled observer. Number of children identified as having abnormal stature (< 0.4th or > 99.6th centile) and abnormal growth rate height standard deviation score (HSDS) change > 0.67). The community survey identified seven (1.4%) children as having abnormal stature (four short, three tall), 11 (2.3%) were identified as "slow growing", and nine (1.9%) increased their HSDS by more than 0.67. These results were comparable to data collected in ideal research conditions. Following the recommendations would not result in an excess number of inappropriate referrals. However, this study highlights several unresolved issues such as interobserver variability and time interval between measurements. A large scale prospective study should be considered to establish realistic and cost-effective criteria before implementation of a national screening programme.


How to differentiate between invasive lobular carcinoma metastasis and type 4 advanced gastric cancer: The importance of immunohistochemistry.
Gastric metastases derived from breast carcinomas and type 4 advanced gastric cancers are often difficult to distinguish because of their similar endoscopic and pathologic findings. Therefore, immunohistochemical analyses are key to diagnosis. Gastric metastases originating from breast carcinomas and type 4 advanced gastric cancers are often difficult to distinguish because of their similar endoscopic and pathologic characteristics. This often delays early intervention and accordingly affects prognosis. Immunohistochemical analyses are important for both diagnosis and treatment of breast carcinomas.


The Combined Strategy for iron uptake is not exclusive to domesticated rice (Oryza sativa).
Iron (Fe) is an essential micronutrient that is frequently inaccessible to plants. Rice (Oryza sativa L.) plants employ the Combined Strategy for Fe uptake, which is composed by all features of Strategy II, common to all Poaceae species, and some features of Strategy I, common to non-Poaceae species. To understand the evolution of Fe uptake mechanisms, we analyzed the root transcriptomic response to Fe deficiency in O. sativa and its wild progenitor O. rufipogon. We identified 622 and 2,017 differentially expressed genes in O. sativa and O. rufipogon, respectively. Among the genes up-regulated in both species, we found Fe transporters associated with Strategy I, such as IRT1, IRT2 and NRAMP1; and genes associated with Strategy II, such as YSL15 and IRO2. In order to evaluate the conservation of these Strategies among other Poaceae, we identified the orthologs of these genes in nine species from the Oryza genus, maize and sorghum, and evaluated their expression profile in response to low Fe condition. Our results indicate that the Combined Strategy is not specific to O. sativa as previously proposed, but also present in species of the Oryza genus closely related to domesticated rice, and originated around the same time the AA genome lineage within Oryza diversified. Therefore, adaptation to Fe2+ acquisition via IRT1 in flooded soils precedes O. sativa domestication.


Separation and maturation of gonadotrophs from 2A8 clonal cells in vitro.
2A8 clonal cells derived from the epithlium of Rathke's pouch of fetal rats were cultured in growth medium supplemented with fresh rat serum, median-eminence extract and 1-thyroxine. Then, in order to isolate gonadotrophs, cyanogen bromide-activated Sepharose whichwas conjugated with LHRH (LHRH-Sepharose) was added to the culture medium. Fourteen days after incubation of 2A8 cells with LHRH-Sepharose, agranular and granular cells were rapidly bound to LHRH-Sepharose when fresh serum had previously been added in the medium. The cytoplasm of granular cells that were bound to LHRH-Sepharose contained spherical secretory granules (200-250 nm in diameter). These cells were similar in morphology to the FSH and LH gonadotrophs described by Kurosumi (1968). Moreover, many of them appeared as hypertrophied cells that resembled "castration" cells. These results demonstrate that LHRH conjugated to Sepharose can be used to separate gonadotrophs from other 2A8 cells, and it is suggested that the hypertrophy of some cells might be due to persistent stimulation by LHRH which is likely bound to receptors on the cell membrane.


High prevalence of refractive errors in a rural population: 'Nooravaran Salamat' Mobile Eye Clinic experience.
The prevalence of myopia and hyperopia and determinants were determined in a rural population of Iran. Population-based cross-sectional study. Using random cluster sampling, 13 of the 83 villages of Khaf County in the north east of Iran were selected. Data from 2001 people over the age of 15 years were analysed. Visual acuity measurement, non-cycloplegic refraction and eye examinations were done at the Mobile Eye Clinic. The prevalence of myopia and hyperopia based on spherical equivalent worse than -0.5 dioptre and +0.5 dioptre, respectively. The prevalence of myopia, hyperopia and anisometropia in the total study sample was 28% (95% confidence interval: 25.9-30.2), 19.2% (95% confidence interval: 17.3-21.1), and 11.5% (95% confidence interval: 10.0-13.1), respectively. In the over 40 population, the prevalence of myopia and hyperopia was 32.5% (95% confidence interval: 28.9-36.1) and 27.9% (95% confidence interval: 24.5-31.3), respectively. In the multiple regression model for this group, myopia strongly correlated with cataract (odds ratio = 1.98 and 95% confidence interval: 1.33-2.93), and hyperopia only correlated with age (P < 0.001). The prevalence of high myopia and high hyperopia was 1.5% and 4.6%. In the multiple regression model, anisometropia significantly correlated with age (odds ratio = 1.04) and cataract (odds ratio = 5.2) (P < 0.001). The prevalence of myopia and anisometropia was higher than that in previous studies in urban population of Iran, especially in the elderly. Cataract was the only variable that correlated with myopia and anisometropia.


Regulation of bradykinin-induced cyclic amp response by quinacrine and prostaglandin E2 and F2 alpha in human synovial fibroblasts.
Bradykinin induces an increment in intracellular cyclic AMP concentrations of human synovial fibroblasts and evokes the release of [3H]arachidonic acid and [3H]-E prostaglandins from human synovial fibroblasts pre-labeled in their phospholipids. Both these bradykinin-induced reactions are inhibited by quinacrine, an inhibitor of phospholipase A activity. The cyclic AMP response of human synovial fibroblasts to bradykinin is potentiated by prostaglandin E2 and inhibited by prostaglandin F2 alpha. These data emphasize the critical role of the prostaglandin system in reactions induced by bradykinin and suggest mechansims by which inflammatory reactions due to bradykinin may be modulated.


Insights into the pyrimidine biosynthetic pathway of human malaria parasite Plasmodium falciparum as chemotherapeutic target.
Malaria is a major cause of morbidity and mortality in humans. Artemisinins remain as the first-line treatment for Plasmodium falciparum (P. falciparum) malaria although drug resistance has already emerged and spread in Southeast Asia. Thus, to fight this disease, there is an urgent need to develop new antimalarial drugs for malaria chemotherapy. Unlike human host cells, P. falciparum cannot salvage preformed pyrimidine bases or nucleosides from the extracellular environment and relies solely on nucleotides synthesized through the de novo biosynthetic pathway. This review presents significant progress on understanding the de novo pyrimidine pathway and the functional enzymes in the human parasite P. falciparum. Current knowledge in genomics and metabolomics are described, particularly focusing on the parasite purine and pyrimidine nucleotide metabolism. These include gene annotation, characterization and molecular mechanism of the enzymes that are different from the human host pathway. Recent elucidation of the three-dimensional crystal structures and the catalytic reactions of three enzymes: dihydroorotate dehydrogenase, orotate phosphoribosyltransferase, and orotidine 5'-monophosphate decarboxylase, as well as their inhibitors are reviewed in the context of their therapeutic potential against malaria.


Desmoid fibromatosis in children and adolescents: a conservative approach to management.
Desmoid fibromatosis is associated with frequent recurrence and significant morbidity, but no metastases. To examine the impact of initial non-operative management on event-free survival (EFS) in children, we reviewed our institutional experience with this tumor. We retrospectively reviewed our institutional database for pediatric cases of desmoid fibromatosis treated between 1970 and 2010. Survival was analyzed using the Kaplan-Meier method and log-rank test. Ninety-three patients were identified, with a median follow-up of 6 years. Median age at diagnosis was 16 years. Forty-seven patients presented with primary tumors, and forty-six had recurrent or progressing disease. Five-year OS was 100%, and 5-year EFS was 31.8%, with a median time to event of 1.48 years. There was no significant difference in 5-year EFS between patients who were managed expectantly and those who initially received treatment (21% versus 34%, P=.09). Sex, race, history of trauma, or familial adenomatous polyposis, multifocality, tumor size, tumor location, and resection status did not correlate with EFS. Our findings support a conservative initial approach in the management of desmoid fibromatosis. In patients at risk for morbid procedures, upfront resection should be reserved for select tumors that demonstrate aggressive growth or cause serious symptoms.


Land-use and land-cover change in Western Ghats of India.
The Western Ghats (WG) of India, one of the hottest biodiversity hotspots in the world, has witnessed major land-use and land-cover (LULC) change in recent times. The present research was aimed at studying the patterns of LULC change in WG during 1985-1995-2005, understanding the major drivers that caused such change, and projecting the future (2025) spatial distribution of forest using coupled logistic regression and Markov model. The International Geosphere Biosphere Program (IGBP) classification scheme was mainly followed in LULC characterization and change analysis. The single-step Markov model was used to project the forest demand. The spatial allocation of such forest demand was based on the predicted probabilities derived through logistic regression model. The R statistical package was used to set the allocation rules. The projection model was selected based on Akaike information criterion (AIC) and area under receiver operating characteristic (ROC) curve. The actual and projected areas of forest in 2005 were compared before making projection for 2025. It was observed that forest degradation has reduced from 1985-1995 to 1995-2005. The study obtained important insights about the drivers and their impacts on LULC simulations. To the best of our knowledge, this is the first attempt where projection of future state of forest in entire WG is made based on decadal LULC and socio-economic datasets at the Taluka (sub-district) level.


Involvement of 5-HT1A receptors in the anxiolytic action of S 14671 in the pigeon conflict test.
In the pigeon conflict test of anxiety, the novel, high efficacy 5-HT1A receptor ligand, S 14671, very potently [minimal effective dose (MED): 0.0025 mg/kg, IM] and markedly (maximal percentage increase relative to control: 17232%) increased punished responding. In analogy, its structural analogue, the 5-HT1A receptor agonist, S 14506, equipotently, though less markedly, augmented punished responding (MED: 0.0025 mg/kg; maximal effect: 5557%). In contrast, the arylpiperazine 5-HT1A receptor agonists, LY 165,163 and tandospirone, increased punished responding only at higher doses (MED: 0.16 and 0.63 mg/kg, respectively), and also with a lesser maximal effect (2065% and 3695%, respectively). Although S 14671 and S 14506 showed a 16-fold separation between doses, increasing punished and decreasing unpunished responding, respectively, this separation was only fourfold for LY 165,163 and tandospirone. The anticonflict activity of S 14671 (0.01 mg/kg) was significantly antagonised by the 5-HT1A receptor antagonist, (-)-alprenolol (10 mg/kg), but not by combined treatment with the selective beta 1 receptor antagonist, betaxolol, and the selective beta 2 receptor antagonist, ICI 118,551. Further, a correlation analysis across each of the above agonists, as well as 8-OH-DPAT, buspirone, and (+)-flesinoxan, revealed a significant correlation for their relative potency in augmenting punished responding and their affinity for 5-HT1A receptors in vitro (r = +0.95, p < 0.001). It is concluded that S 14671 is an exceptionally potent and efficacious ligand in the pigeon conflict test and that its anxiolytic action reflects the activation of 5-HT1A receptors.


Effects of ondansetron, granisetron, ramosetron, and azasetron on human neutrophil functions.
Neutrophil functions play an important role in the antibacterial or antitumor host defense system. Ondansetron, granisetron, ramosetron, and azasetron are often used in gynecological patients as a prophylaxis against postoperative emesis or chemotherapy-induced emesis. In this study, using an ex vivo system, we have shown that these antiemetics at clinically relevant concentrations had no effect on superoxide (O(-)(2)) and hydrogen peroxide (H(2)O(2)) production of neutrophils, although high doses of these drugs significantly inhibited it to a similar degree. The drugs failed to impair chemotaxis or phagocytosis and to scavenge O(-)(2) or H(2)O(2) generated by an acellular system. Inhibition of the reactive oxygen species production may be due to attenuation of calcium elevation in neutrophils with these antiemetics. Our findings suggest that we are able to use these antiemetics in gynecological patients with cancer or those undergoing surgery without great caution.


Co-remediation of cadmium-polluted soil using stainless steel slag and ammonium humate.
This study investigated the remediation of cadmium-polluted soil using a combination of stainless steel slag and ammonium humate. These remedial agents were added to an artificially polluted garden soil to inhabit cadmium toxicity in soil by changing the physical and chemical properties of soil in a pot experiment. The results showed that the co-application of ammonium humate and stainless steel slag significantly decreased the total and available soil cadmium concentrations, with maximum decreases of 16.30% and 58.04%, respectively. The co-application of an adequate dose of these remedial agents can significantly increase soil pH. The soil organic matter and cation exchange capacity, as well as the amount of soil aggregates, were also significantly increased by the addition ammonium humate, but not stainless steel slag.


Childhood choroid plexus neoplasms. A study of 14 cases less than 2 years old.
Fourteen children less than 2 years old with choroid plexus papilloma (CPP) were studied. Of these patients nine had the tumor in the lateral ventricles (LV), three in the fourth ventricle (4th V), one in the third ventricle (3rd V) and one in the third and left lateral ventricle (LLV). Ten cases showed benign CPP, three cases malignant CPP, and one case had a venous malformation of the choroid plexus (VMCP). Computed tomography (CT) was the best method for neuroradiological study, although a very small CPP in the 3rd V was not detected in an early study. Malignant and benign CPP can be differentiated with CT, especially if the study is performed with contrast media. Pneumoencephalography must be rejected because it is very dangerous and may be the cause of death in some cases. The follow-up of patients with CPP showed a poor prognosis, even after correctly removing the tumor and inserting a shunt.


Risk of Death Associated With Intravitreal Anti-Vascular Endothelial Growth Factor Therapy: A Systematic Review and Meta-analysis.
Although intravitreal anti-vascular endothelial growth factor (VEGF) treatment represents the first-line therapy for many retinal diseases, the issue of their systemic safety is debatable. To assess whether intravitreal anti-VEGF therapy might be associated with increased risk of mortality and which variables are associated with the increase. PubMed, MEDLINE, and Embase databases, the Cochrane Library, and ClinicalTrials.gov were systematically searched from inception to May 6, 2019. Randomized clinical trials comparing intravitreal anti-VEGF treatment with control groups and with follow-up of at least 6 months were selected. Data were independently collected by 2 investigators. Meta-analyses were conducted using the frequentist and Bayesian methods. For the frequentist approach, random- and fixed-effects models were used, with random-effects models considered the primary technique. Odds ratios (ORs) with 95% CIs were computed. For the bayesian approach, uninformative and informative priors were used. Odds ratios with 95% credible intervals (CrIs) were computed. Meta-regression analyses were based on random-effects models. The primary outcome measure was the all-cause death rate. Secondary outcomes included meta-regression analyses on the following variables: type of drug, number of injections, follow-up time, diagnosis, and cardiovascular risk. Of 2336 studies identified, 34 unique studies with 8887 unique participants were included in the present meta-analysis. For the frequentist analysis, fixed- and random-effects models yielded similar estimates (ORs, 1.34 [95% CI, 0.95-2.07; P = .09] and 1.34 [95% CI, 0.89-2.01; P = .17], respectively). For the Bayesian approach, noninformative and informative priors yielded similar results (ORs, 1.34 [95% CrI, 0.79-2.34; 0.13 probability of OR≤1.00] and 1.40 [95% CrI, 0.82-2.32; 0.11 probability of OR≤1.00], respectively). Meta-regression analyses showed the following risk for 1 injection more: frequentist OR of 1.12 (95% CI, 1.04-1.22; P = .005) and Bayesian OR of 1.06 (95% CrI, 0.98-1.15; 0.06 probability of OR≤1.00). In this study, no difference was found in the mortality rate between intravitreal anti-VEGF treatment and control groups. Additional data seem warranted to determine whether the mortality rate is increased in patients receiving a greater number of injections.


Endovascular treatment of unruptured cerebral aneurysms.
76 consecutive patients with 78 unruptured cerebral aneurysms underwent endovascular therapy from July 1999 to May 2004 in our institute. For the wide-necked aneurysms, the remodeling technique, double microcatheter technique, or stent-assisted coil embolization was used, while a parent artery occlusion or covered stent was applied for the giant or fusiform aneurysms. Immediate angiographical results demonstrated 33 complete occlusions, 26 neck remnants, and 14 dome fillings. Four cases were treated with parent occlusion or stenting only, and one case was not treated with embolization but with clipping due to the rupture of the aneurysm during coil embolization. Immediate angiographic findings demonstrated that in aneurysms between 5 to 10 mm, the rate of complete occlusion was 48%, that of neck remnants 33%, and that of dome fillings 27%. In aneurysms between 11 to 25 mm, the rate of complete occlusion was 14%, that of neck remnants 28%, and that of dome fillings was 58%. In the angiographic follow-up results, all aneurysms smaller than 5 mm showed complete occlusion. In aneurysms between 5 to 10 mm, 74% of the aneurysms showed complete occlusion, and 21% showed neck remnants, and 5% showed dome filling. In aneurysms between 10 to 24 mm, 25% showed complete occlusion, while 75% showed dome filling. The overall mortality rate was 0% and the morbidity rate was 3.7% (2 major strokes, 1 minor stroke) at 30-days after embolization. In the clinical follow-up study, one case of a large basilar tip aneurysm caused a fatal rupture 28 months after the initial embolization. Endovascular therapy was performed on the unruptured aneurysms and was found to be an acceptable treatment, except for durability in cases of large aneurysms.


Questionnaire survey on the state of routine echocardiographic examinations in Japan: second report.
We mailed questionnaires to 748 registered medical sonographers [RMSs (cardiology)] to gather information for a large-scale survey of RMSs in May 2000. We wanted to evaluate the current state of routine echocardiography in Japan. Altogether, 530 (70.9%) of these sonographers responded; 18 respondents employed by equipment manufacturers were excluded from the start of the study, and 20 others later found to be employed by equipment manufacturers were also excluded. Responses from all personnel at a single institution were treated as a single response; 436 institutions were thus included in the survey. Most or all examinations were carried out by sonographers at 77.3% of the responding institutions but were performed mainly by physicians at 11.1% of the institutions. At least 80% of sonographer or physician working hours were used for echocardiographic examination at 18.9% of the surveyed institutions, whereas up to half the working hours were devoted to echocardiographic examinations at 67.0% of the institutions. The most frequently reported examination time was 30-40 min [35.6% (n = 116) of the institutions], whereas 32.8% (n = 107) of the institutions indicated durations of 10-20 min per examination. Left ventricular (LV) dimensions and wall thickness were measured on M-mode images in all patients at 14.1% (n = 59) of the institutions and mainly on M-mode images but from two-dimensional echocardiography in problematic patients at 74.2% (n = 311) of the institutions. The LV ejection fraction was calculated from LV dimensions at 55.7% (n = 205) of the institutions and from the LV cross-sectional area at 44.3% (n = 163) of the institutions. The LV ejection fraction was estimated visually at 57.0% of the institutions. Only 5.5% (n = 22) of the facilities always scored the wall motion. Pulsed Doppler echocardiography was used to assess LV inflow in all patients at 65.9% of the institutions; regurgitation and shunting were always assessed quantitatively at only 2% (n = 8). Comments concerning image quality were reported in all cases or in cases of poor image quality at 98% of the institutions, and the sonographer was also involved in writing the diagnostic report at 94% of institutions. Echocardiography is less expensive than other diagnostic imaging methods, and its importance is thus likely to continue to increase. Echocardiographic examinations should be carried out by skilled RMSs and physician echocardiographers; and an accurate, readily comprehensible report of the findings should be provided promptly to the referring physician. More such surveys are required to ensure that these practices are adopted.


The Research Progress of Taxol in Taxus.
Taxus is a valuable woody species with important medicinal value. The bark of Taxus can produce taxol, a natural antineoplastic drug that is widely used in the treatment of breast, ovarian and lung cancers. However, the low content of taxol in the bark of Taxus can not meet the growing clinical demands, so the current research aims at finding ways to increase taxol production. In this review, the research progress of taxol including the factors affecting the taxol content, biosynthesis pathway of taxol, production of taxol in vitro and the application of multi-omics approaches in Taxus as well as future research prospects will be discussed. The taxol content is not only dependent on the species, age and tissues but is also affected by light, moisture levels, temperature, soil fertility and microbes. Most of the enzymes in the taxol biosynthesis pathway have been identified and characterized. Total chemical synthesis, semi-synthesis, plant cell culture and biosynthesis in endophytic fungi have been explored to product taxol. Multi-omics have been used to study Taxus and taxol. Further efforts in the identification of unknown enzymes in the taxol biosynthesis pathway, establishment of the genetic transformation system in Taxus and the regulatory mechanism of taxol biosynthesis and Taxus cell growth will play a significant role in improving the yield of taxol in Taxus cells and plants.


Ozonation products of triclosan in advanced wastewater treatment.
Triclosan is an antimicrobial agent widely used in many household and personal care products. Widespread use of this compound has led to the elevated concentrations of triclosan in wastewater, wastewater treatment plants and receiving waters. In this study removal of triclosan by aqueous ozone was investigated and the degradation products formed during ozonation of an aqueous solution of triclosan were analyzed by GC-MS and HPLC-MS/MS. The following transformation products have been identified: 2,4-dichlorophenol, chloro-catecol, mono-hydroxy-triclosan and di-hydroxy-triclosan during treatment process. Cytotoxicity and genotoxicity of pure triclosan and 2,4-dichlorophenol have been investigated and the results showed reduced genotoxic effects after ozonation, though the respective chlorophenol is harmful to aquatic organisms.


Dietary ARA Improves COX Activity in Broodstock and Offspring Survival Fitness of a Model Organism (Medaka Oryzias latipes).
A 3-week feeding trial was conducted in medaka broodstock (age five months) to examine the effect of dietary arachidonic acid (ARA) level (range: 4-23 mg g-1 of total fatty acids (TFAs)) on fertility, cyclooxygenase (COX) activity, egg size, sperm motility parameters, hatching rate and weight of hatch, survival and growth of larvae. After spawn induction and dietary exposure to 4 mg ARA g-1 TFA, broodstock were fed a diet containing ARA in the amounts: 4 (continued, as control), 5, 14 and 23 mg g-1 TFA. COX1 activity in the liver and the number of COX2-positive cells in the ovaries was increased in females fed the diets containing the two highest amounts of ARA. The highest sperm motility parameters were observed in males fed a diet containing 23 mg ARA g-1 TFA. The hatchability rate and bodyweight of hatchlings were higher in the group obtained from broodstock fed a diet containing 23 mg ARA g-1 TFA (79% and 0.66 mg fish-1, respectively) compared with 4 mg ARA g-1 TFA (50% and 0.40 mg fish-1). The average mortality of offspring obtained from this group at 7 days post hatching was significantly higher than that of all other groups.


Stability improvement for dried droplet pretreatment by suppression of coffee ring effect using electrochemical anodized nanoporous tin dioxide substrate.
A novel nanoporous analytical platform is reported to improve the stability of the dried droplet method (DDM). This nanoporous platform was made of tin dioxide (Np SnO2) substrate by electrochemical anodization from tin (Sn) slide. The DDM is a widely used sample pretreatment in analytical chemistry that involves placing a droplet of solution onto the substrate and drying for analytical testing. However, during the droplet drying process, the solutes would converge at the droplet edge and cause inhomogeneous solutes distribution. This is the coffee ring effect (CRE). The Np SnO2 has irregular nanopores, which allows droplet solutions to penetrate into the substrate rather than spreading out, effectively suppressing CRE. Theoretical models were built to explain the formation of CRE on blank tin (Sn) substrate and suppression of CRE on Np SnO2. Better results were obtained in detecting lithium (Li) using the Np SnO2 by laser-induced breakdown spectroscopy (LIBS). The line scanning results indicated that the Li emission line (670.8 nm) intensities on Np SnO2 substrate had lower relative standard deviation (RSD = 3.3%) than those on Sn substrate (RSD = 31.5%), which illustrate suppression of CRE and stability improvement on Np SnO2 substrate. Furthermore, Li calibration curves were built for LIBS with DDM. The curve using Np SnO2 substrate had better linearity (R2 = 0.997), higher precision (RSD = 4.2%), and higher sensitivity (LOD = 0.13 mg/L) than that by Sn substrate (R2 = 0.954, RSD = 17%, and LOD = 1.21 mg/L). All in all, the anodic Np SnO2 substrate can suppress CRE in DDM and hence improve the stability and precision of subsequent analysis. Graphical abstract.


Polymerase chain reaction identification of Bacillus sporothermodurans from dairy sources.
A new polymerase chain reaction (PCR) method for the identification of Bacillus sporothermodurans strains from sterilized or ultrahigh temperature-treated milk and milk products and from other non-milk sources and environments, including the dairy farm. Two strains from raw milk and feed concentrate could be allocated to B. sporothermodurans based on 16S rDNA sequencing and DNA-DNA hybridization results. Two specific PCR primers were derived from the 16S rRNA gene of B. sporothermodurans. The PCR identification method was validated using a collection of B. sporothermodurans strains from different sources and on a large collection of dairy and non-dairy Bacillus spp. and other relevant taxa. This PCR method was used as a screening method for strains with very heat-resistant endospores, isolated at the dairy farm level after heat treatment for 30 min at 100 degrees C. Seventeen strains isolated at the dairy farm were identified as B. sporothermodurans. They originated mainly from feed concentrate and also from soy, pulp and silage. The PCR identification method described here can, therefore, contribute to a better understanding of the route by which B. sporothermodurans contaminates raw and/or heat-treated milk.


Disinfection and sterilization: an overview.
All invasive procedures involve contact by a medical device or surgical instrument with a patient's sterile tissue or mucous membranes. The level of disinfection or sterilization is dependent on the intended use of the object: critical (items that contact sterile tissue such as surgical instruments), semicritical (items that contact mucous membrane such as endoscopes), and noncritical (devices that contact only intact skin such as stethoscopes) items require sterilization, high-level disinfection, and low-level disinfection, respectively. Cleaning must always precede high-level disinfection and sterilization.


Cell-surface antigens of developing rat cerebellar neurons: identification with monoclonal antibodies.
Three monoclonal antibodies (Mab's), named 3C5.59, 3G5.34, and 3G6.41, that recognize cell-surface antigens found on embryonic and postnatal neurons were selected for study from among a group generated against adult rat synaptic plasma membranes (SPM's). Immunofluorescence staining with these 3 antibodies showed strong reactivity of the processes and much weaker staining of the cell bodies of the small neurons cultured from early postnatal rat cerebella. Mab 3G6.41 also reacted with flat astrocyte-like cells cultured from cerebellum. In contrast Mab's 3C5.59 and 3G5.34 appeared to specifically recognize only the neurons in these cultures. In situ staining of cryostat sections with 3G5.34 and 3G6.41 demonstrated immunoreactivity that was predominantly localized to the molecular layer of the cerebellum in the early postnatal through adult stages, in agreement with the strong staining of neurites seen in primary neuronal cultures. Quantitative analysis of Mab binding to particulate protein preparations from various tissues of the adult rat indicated that each of the antigens is restricted to the nervous system in the adult. Binding studies also indicated that each antigen was enriched approximately 1.5-fold in the SPM fractions compared to total particulate fractions from cerebellum. All 3 Mab's recognize membrane-bound molecules that can be solubilized by non-ionic detergent. Mab 3G6.41 immunoprecipitated two polypeptides of 140,000 and 185,000 apparent molecular weight from detergent-solubilized cerebellar cells that were surface-iodinated in culture. These antibodies should prove useful in the further analysis of the expression and function of individual cell surface antigens during the differentiation of cerebellar granule cells.


Percutaneous Ultrasound-Guided Cryoablation for Symptomatic Plantar Fibromas.
Here, we report our experience in treating painful plantar fibromas with percutaneous cryoablation. We retrospectively identified patients with symptomatic plantar fibromas who underwent percutaneous ultrasound-guided cryoablation between June 2014 and June 2015. In total, four patients (two male, two female) with five plantar fibromas undergoing a total of seven ablation procedures were identified. Each procedure was performed under general anesthesia using a single freeze-thaw cycle. The electronic medical record, procedure reports, and pain scores from a brief pain inventory administered before and after treatment were reviewed. Average and worst pain in 24 h, and time to peak symptom improvement post-procedure were compared. Complications were reviewed using the SIR classification. Five plantar fibromas were treated (mean size 2.2 ± 1.6 cm). Four of five lesions were present for more than 6 years, and 1/5 was present for less than 1 year. Surgical excision was previously performed on 3/5 lesions, all with short-term recurrence. Mean worst pain score in 24 h and average pain score in 24 h (scale of 10) at initial evaluation were 7.1 ± 1.8 and 5.8 ± 1.9, reduced after cryoablation to 0.8 ± 0.8 and 0.4 ± 0.6, respectively. Average time to symptom improvement was 2.8 ± 0.98 weeks (range 2-4 weeks). All patients reported improved ambulation and weight-bearing, and complete cessation of pain medication after treatment. The improvement was sustained on follow-up at 12 months. No major complications occurred. Minor complications occurred in 3/5 patients. Early experience with percutaneous ultrasound-guided cryoablation to treat painful plantar fibromas suggests that it is a safe and effective treatment option, with early and near-complete symptom improvement.


The pericontused cortex can support function early after TBI but it remains functionally isolated from normal afferent input.
Traumatically injured brain functional connectivity (FC) is altered in a region-dependent manner with some regions functionally disconnected while others are hyperconnected after experimental TBI. Remote, homotopic cortical regions become hyperexcitable after injury, and we hypothesize that this results in increased trans-hemispheric cortical inhibition, preventing reorganization of the primary injured hemisphere. Previously we have shown that temporary silencing the contralesional cortex at 1wk normalizes affected forelimb behavioral use, but not at 4wks. To investigate the potential mechanism for this and to determine whether this occurs due to restoration of afferent pathway FC, and/or reorganization of brain circuits, we probed forelimb circuit function with sensorimotor task-evoked-fMRI, resting state fMRI seed-based analysis, and exploratory structural equation modelling (SEM) of directed causal connections due to forelimb task at 1 and 4wks post-injury after temporary, contralateral silencing with intraparenchymal injection of muscimol versus vehicle, as well as from sham rats. As predicted, silencing at 1wk and 4wks post-injury decimated the contralesional cortical forelimb map evoked by stimulation of the opposite, unaffected forelimb compared to vehicle-injected injured rats indicating the success of the intervention. Surprisingly however, this also resulted in activation of the pericontused cortex ipsilateral to the stimulated forelimb at 1wk, yet this same region could not be activated by directly stimulating the opposite, injury-affected forelimb. Underpinning this were significant increases in interhemispheric FC at the level of the cortex but decreases within subcortical regions. Causal SEM analysis confirmed increased corticothalamic connectivity and suggested changes from and to bilateral thalamus are important for the effect. At 4wks post-injury only cortical increases in FC were found in response to silencing indicating a less flexible brain, and ipsilesional cortex evoked activity was mostly absent. The absence of a reinstatement of ipsilesional evoked activity through normal pathways by temporary neuromodulation despite prior data showing behavioral improvements under the same conditions, indicates that while the pericontused cortex does retain function initially after injury, it is too functionally disconnected to be controlled by normal afferent input. More significant alterations in cross-brain FC during neuromodulation at 1wk compared to 4wk post-injury, suggest that more distributed brain activity accounts for prior behavior improvements in sensorimotor function, and that hemispheric imbalance in function is causally involved in early loss of sensorimotor function in this TBI model.


Microglia express CCR5, CXCR4, and CCR3, but of these, CCR5 is the principal coreceptor for human immunodeficiency virus type 1 dementia isolates.
Microglia are the main human immunodeficiency virus (HIV) reservoir in the central nervous system and most likely play a major role in the development of HIV dementia (HIVD). To characterize human adult microglial chemokine receptors, we analyzed the expression and calcium signaling of CCR5, CCR3, and CXCR4 and their roles in HIV entry. Microglia expressed higher levels of CCR5 than of either CCR3 or CXCR4. Of these three chemokine receptors, only CCR5 and CXCR4 were able to transduce a signal in microglia in response to their respective ligands, MIP-1beta and SDF-1alpha, as recorded by single-cell calcium flux experiments. We also found that CCR5 is the predominant coreceptor used for infection of human adult microglia by the HIV type 1 dementia isolates HIV-1DS-br, HIV-1RC-br, and HIV-1YU-2, since the anti-CCR5 antibody 2D7 was able to dramatically inhibit microglial infection by both wild-type and single-round luciferase pseudotype reporter viruses. Anti-CCR3 (7B11) and anti-CXCR4 (12G5) antibodies had little or no effect on infection. Last, we found that virus pseudotyped with the DS-br and RC-br envelopes can infect cells transfected with CD4 in conjunction with the G-protein-coupled receptors APJ, CCR8, and GPR15, which have been previously implicated in HIV entry.


Molecular basis of the TaqI p49a,f polymorphism in the DYS1 locus containing DAZ genes.
The previously described TaqI p49a,f polymorphism at the DYS1 locus in the non-recombinant part of the Y chromosome is widely exploited to investigate many facets of human population genetics. It has been shown that the DYS1 locus corresponds to the four DAZ genes in the AZF-c region of the Y chromosome. As the DNA sequence of the DAZ genes is known in its entirety, it is now possible to establish correspondences between the main Southern polymorphic TaqI bands (A, C, D, F and I) at the DYS1 locus and TaqI fragments deduced from the sequence, by way of comparing band sizes and sequence homologies between hybridized fragments. Transitions between polymorphic forms for each variable TaqI fragment can be explained regarding the restriction maps, by postulating a parsimonious number of TaqI site losses during human evolution. Most of the codon changes caused by TaqI site losses located in the exons of the four DAZ genes have potentially high selective values.


Condylomatous lesions of the upper aerodigestive tract.
Condyloma acuminatum is one of four types of common human verrucous lesions that are of viral etiology. Also known as "moist wart," condyloma acuminatum is most often seen on the mucosal surfaces of the anogenital area. However, occurrences in the mucosal lined areas of the head and neck region are quite rare. Since 1901, 30 cases of condylomatous lesions have been reported in the upper aerodigestive tract, occurring mainly in the various regions of the oral cavity. Eighteen of the cases were confirmed by histopathologic documentation, while the remainder were anecdotal. We have recently encountered six new cases of condyloma acuminatum, verified by histologic examination. One occurred on the tongue, another in the tonsillar fossa, one in the hypopharynx and three on the vocal cords. We present these cases and review the previously reported cases. In addition, we will discuss the differential diagnosis of these lesions, and their importance to the practicing otolaryngologist.


Rheology of dispersions and emulsions composed of chia mucilage and the application of chia in food.
Chia mucilage (CM) is an emerging resource in food applications. However, the mechanism of this biopolymer as a stabilizer/emulsifier ingredient has not yet been well defined. A non-uniform viscoelastic tridimensional network was observed on emulsions with CM, while the surface activity of the CM ingredient has been associated with its protein content. To understand its functionality in food, this review focused on discussing and summarizing the rheological properties of dispersions and emulsions composed of CM under different conditions, such as pH, temperature, salt content, and mucilage content. For example, emulsions and dispersions with CM showed pseudoplastic behavior. An increase in the CM concentration increased the viscosity and the consistency index and decreased the behavior index. The consistency index of dispersions with CM increased with pH. The future evaluation of emulsions and dispersions properties, such as viscoelastic properties and microstructure, is particularly important for the successful use of CM in the food industry. The principal studies have evaluated the use of CM in dairy and meat systems as an emulsifier, stabilizer, or lipid replacer. The nutritional quality of the products with CM was maintained or improved, but sometimes an undesirable darkening was observed. Future evaluation of the cold extraction method of CM might improve the color and overall sensory acceptability of food products with CM. Integrated chia seed processing, including mucilage, oil, and protein extraction could be carried out to make chia seed industrial processing viable. © 2022 Society of Chemical Industry.


[Ultrastructure of the smooth muscle cells of the femoral artery in rats exposed to vibration].
Electron microscopic study of femoral arteries of white rats exposed to prolonged general vibration at a frequency of 100 Hz with an amplitude of 0.5-0.7 mm has been performed. Light and dark smooth muscle cells, as well as unchanged cells have been found in the vascular media of experimental animals. Light cells are swollen with destroyed myofilaments and great number of microtubules in cytoplasm. Dark cells are characterized by coagulation necrosis and melting of myofilaments. Vibration was shown to cause marked structural changes in smooth muscle cells mitochondria: destruction of internal and external membranes, increasing matrix osmophilia or swelling of mitochondria accompanied by crista fragmentation, as well as matrix clarification and disappearance. Morphometric analysis indicates a considerably decreased energy production by smooth muscle cell mitochondria. It has been concluded that vibrations have a damaging effect on medial smooth muscle cells of the femoral artery in the experimental animals.


Logical Framework Approach a Platform for Integrating the Mental Health and Nutritional Care for Controlling the Covid-19 Pandemic.
Coronavirus infection (COVID-19) is spreading rapidly in the world beyond the health care capacity. The World Health Organization (WHO) has announced an emergency state that needs quick and effective actions. In the lack of specific medicine and vaccine, integration of mental health and nutritional care in the platform of a powerful managerial technique named the "Logical Framework Approach" (LFA) could be helpful for successful control of this pandemic. The strengths of the LFA for coronavirus management program are stakeholders' involvement, integrative teamwork in research and medical procedures, as well as Inter-sectoral cooperation. The related organizations like WHO and ministries of health of every country could easily adopt this approach and act more efficiently to manage this pandemic.


Developmental profile of chromogranin, hormonal peptides, and 5-hydroxytryptamine in gastrointestinal endocrine cells.
In this immunocytochemical study, we have analyzed the developmental profile and phenotypic expression of the endocrine cell antigens chromogranin, 5-hydroxytryptamine, gastrin/cholecystokinin, cholecystokinin (9-20), somatostatin, somatostatin 28 (1-14), somatostatin cryptic peptide, glucagon, glucagonlike peptides 1 and 2, glicentin, peptide YY, glucose-dependent insulinotropic peptide, secretin, neurotensin, and substance P in human fetal stomach and intestine. All currently identifiable endocrine cell types were detected by 10 wk of gestation. Immunostaining for the endocrine cell marker chromogranin revealed abundant endocrine cells in the earliest specimens (8 wk of gestation) with a relatively higher frequency in both proximal duodenum and distal colon/rectum compared with other areas. Quantification of endocrine cells showed an increase with age that was roughly parallel to the growth of the gut as a whole. These studies show that the diversity of the endocrine component of the gut appears to be established by 10 wk of gestation and that gut activity is preceded by the development of a fully differentiated endocrine component, which may subserve or even initiate the onset of functional maturity.


miR181a protects against angiotensin II-induced osteopontin expression in vascular smooth muscle cells.
Osteopontin (OPN) is a multifunctional protein found in abundance in atherosclerotic plaques. Angiotensin II (Ang II) promotes atherosclerosis by inducing adhesion and migration of vascular smooth muscle cells (VSMCs). MicroRNAs (miRNAs) are critical regulators of protein expression. However, the relationship between Ang II, miRNAs and OPN has yet to be fully explored. Using cultured VSMCs, we found that Ang II increased cellular OPN protein expression 4 h after treatment by 420 ± 54% (p < 0.03) in a translation dependent manner. Sequence analysis revealed a putative binding site for mir181a and raised the possibility that miR181a is a potential regulatory mechanism for OPN expression. We demonstrated that Ang II decreased miR181a expression by 52 ± 7% (p < 0 .0001) and overexpressing miR181a inhibited Ang II induced increases in OPN protein expression by 69 ± 9% (p < 0.05). Furthermore, we demonstrated that miR181a is functionally important in that overexpression of miR181a inhibited VSMCs adhesion to collagen in response to Ang II as compared to controls by 36 ± 4%. (p < 0.05) CONCLUSIONS: These results demonstrate that miR181a regulates OPN expression and that altering miR181a expression may be a novel therapeutic approach to modulate OPN protein expression.


Long-term survival after female pelvic organ-sparing radical cystectomy versus standard radical cystectomy: a multi-institutional propensity score-matched analysis.
The application of pelvic organ preserving-radical cystectomy (POPRC) in female patients with bladder cancer has attracted more and more attention in recent years. In the current study, the authors aim to compare the long-term oncological outcomes of POPRC versus standard radical cystectomy (SRC) in a large multicenter retrospective cohort. Data on female patients with bladder cancer who underwent POPRC or SRC in January 2006 and April 2018 were included from three Chinese urological centers. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival and recurrence-free survival. To decrease the effect of unmeasured confounders associated with treatment selection, 1:1 propensity score matching was performed. Among the 273 enrolled patients, 158 underwent POPRC (57.9%), and 115 underwent SRC (42.1%). The median follow-up time was 38.6 (15.9-62.5) months. After propensity score matching, each cohort included 99 matched patients. The OS ( P =0.940), cancer-specific survival ( P =0.957), and recurrence-free survival ( P =0.476) did not differ significantly from the two matched cohorts. Subgroup analysis confirmed that the OS was similar between the patients treated with POPRC and SRC across all subgroups examined (all P > 0.05). In multivariable analysis, the surgical method (SRC vs. POPRC) was not an independent risk factor for OS (Hazard ratio 0.874, 95% CI 0.592-1.290; P =0.498). The results showed that no significant difference in long-term survival was determined between female patients undergoing SRC and those undergoing POPRC.


Effect of magnetic susceptibility contrast medium on myocardial signal intensity with fast gradient-recalled echo and spin-echo MR imaging: initial experience in humans.
To show the effect of dysprosium diethylenetriaminepentaacetic acid bis-methylamine injection on the images of normal human myocardium. T2-sensitive fast gradient-recalled echo (GRE) (repetition time [TR], 10.8 msec; echo time [TE], 4.2 msec) and spin-echo (SE) (TR, three RR intervals; TE, 60 msec) magnetic resonance (MR) imaging with driven equilibrium-preparation pulse was used to produce T2 contrast material enhancement. The contrast agent was injected into 12 healthy subjects at doses of 0.05, 0.1, 0.2, 0.4, and 0.6 mmol/kg. Driven equilibrium-prepared GRE images showed a transient decrease of myocardial signal intensity at doses of 0.2-0.6 mmol/kg. Postcontrast T2-weighted SE images showed a myocardial signal attenuation (30%-45% decrease) at a dose of 0.4 mmol/kg or higher. Dynamic MR imaging with a magnetic susceptibility contrast medium can be used to monitor the first pass of contrast media through human myocardium with a conventional MR imager and a fast GRE sequence.


[Sheltered living groups : Hybrid form of care services in legal conflict situation].
Sheltered living groups are enjoying great popularity in Germany. They represent an alternative to home care on the one hand and to nursing homes on the other hand. Under German law they face a conflict situation and must fulfil many legal requirements, which confront the foundation and operation with legal barriers. The legal situation and legal practice vary significantly from one federal state to another. Infrastructure development of sheltered living groups as local care services can be found within a helpful governance of advisory structures. The different legal requirements, which apply to sheltered living groups in Germany are outlined in this article. The hybridity, which characterizes sheltered living groups is also connected with a hybrid legal framework of regulations.


[Role of cilostazol in the sequential therapeutic spectrum of the peripheral arterial occlusion disease (PAOD)].
Cilostazol (Pletal(®), UCB Pharma, Monheim, Deutschland) has been successfully established since its inauguration on the German market in 2007, which is associated with a considerable distribution, in particular, in angiologic patients. However, vascularsurgical specifics in the use of Cilostazol are still lacking. The aim of this very compact short overview is (based on a selective literature search and own clinical experiences over the years) to characterize mechanism of action, use and expectable therapeutic effect of Cilostazol in the challenging management of exclusively vascularsurgcial patients with peripheral arterial occlusion disease (PAOD). Cilostazol inhibits phosphodiesterase 3 and platelet aggregation in a reversible manner with a dose-effect association, has vasodilating potential and a positive inotropic effect but provides a selective effect on the platelets, muscle and endothelial cells of the vascular wall via an intracellular increase of cAMP; in addition, there is an antiproliferative effect, it promotes neoangiogenesis, inhibits apoptosis and generation of endothelial adhesion molecules - taken together, it can be considered antiatherogenic ("anti-arterioscleroticum"). From a clinical point of view, Cilostazol is indicated in stage IIb of PAOD (Fontaine); its recommended dosage is 2x100 (reduced in case of moderate side effects, 2x50) mg with detectable prolongation of subjective (reported by the patient) and objective walking distance (but not in smokers [!]; ABI-based measurement of the effect not suitable) and partially with an improval of the quality of life (associated with a prolonged but steadily improving therapeutic effect from the 4th to the 6th week until the 6th to the 12th month). The profile of side effects is broad but mostly short-term and dominated by headache [~ 30 %] and diarrhoea [~ 15 %]). While Cilostazol not only plays a beneficial role in the setting to be used in the primary arteriosclerotic course of PAOD (called sequential therapeutic preoperative course), it appears also to provide great effect in case of a re-manifestation of claudication (approaching stage IIb according to Fontaine's classification) after previous image-guided interventional or vascularsurgical treatment (suitable conservative mid-term intermediate therapy), i) resulting in a flexible physician's tool of the angiologic and vascularsurgical setting of an outpatient clinic, and ii) which reduces significantly the number of re-interventions or prolonges the time interval(s) in between. This might finally be relevant in the perspective for an amputation-free survival.


Immature stages of Trichonema spp as a cause of diarrhoea in adult horses in spring.
Several incidents of diarrhoea and loss of weight occurred in adult horses during the spring of 1976. Detailed investigation of one typical case suggested that maturation of inhibited larvae of Trichonema spp was responsible.


Scutellistacaerulea (Fonscolombe, 1832) (Hymenoptera: Pteromalidae), new to New Zealand for the second time!
In 1921, Scutellistacaerulea was imported and released in Nelson, New Zealand, for the biological control of pest scale insects. It was thought to have failed to establish, and is therefore currently considered to be absent from the New Zealand fauna. On 17 April 2013, a live specimen was captured in the wild in Auckland.


Antioxidant or pro-oxidant and glutathione transferase P1-1 inhibiting activities for Tamarindus indica seeds and their cytotoxic effect on MCF-7 cancer cell line.
The multidrug resistance (MDR) of cancer cells is a major obstacle to cancer treatment. Glutathione S-transferase Pi (GSTP1-1) catalyzes the conjugation of glutathione with anticancer drugs and therefore reduces their efficacy. Phenolic compounds have the potential to inhibit GST P1-1 activity, which is a promising goal to overcome MDR and increase the efficacy of chemotherapy. Three fractions (dichloromethane, ethyl acetate, and n-butanol) were prepared from Tamarindus indica seeds to determine their phenolic and flavonoid properties as well as their antioxidant/pro-oxidant properties. The n-butanol fraction displayed the highest levels of phenol ( 378 ± 11.7 mg gallic acid equivalent/g DW) and flavonoids (83 ± 6.0 mg rutin equivalent/g DW). Inhibiting effects on purified GSTP1-1 activity in human erythrocytes (eGST), placenta (pGST), and hGSTP1-1 have been studied. The n-butanol fraction was the most effective in inhibiting eGST, hGSTP1-1, and pGST with IC50 values of 3.0 ± 0.7, 4.85 ± 0.35, and 6.6 ± 1.2 μg/ml, respectively. Cellular toxicity was investigated for the T. indica n-butanol fraction on various human cancerous cell lines. The only ones affected were MCF-7 cell lines (72%) and HePG2 (52%) indicated cytotoxicity. The value of IC50 is 68.5 μg/ml of T. indica n-butanol fraction was observed compared to 1.7 μg/ml tamoxifen in MCF-7 cell lines. The combination of treatment of T. indica extract with the medicinally approved drug tamoxifen had unexpected effects; complete elimination of the cytotoxic inhibition effect of tamoxifen and the plant extract was observed. However T. indica extract has a cytotoxic effect on the MCF-7 cell line; in certain situations, plant products can have an opposite effect to the intended drug, which decreases the impact of the drug.