Experimental mixed CNS infections in mice caused by three Ixodes ricinus transmitted Arboviruses.
Approximately 12-day-old mice were infected intracerebrally with tick-borne encephalitis (TBE) virus (strain Hypr), Unkuniemi virus (strain By E50) and Tribec virus, as single virus inoculations, coinfections with two or three viruses, and sequential infections with two or three viruses at 24-hour intervals. The effect of mixed infections on mortality, morbidity and average survival time was recorded. The main findings were that: 1. Some mixed infections with TBE and UUK viruses reduced the mortality and acute morbidity significantly as compared to single infections with each virus. The average survival times were lengthened. 2. Mixed infections with TBE and Tribec did not affect the 100% mortality of TBE. 3. Mixed infections with UUK and Tribec seemed to result in a cumulative effect of the two viruses. 4. With triple co-infections (TBE + Tribec + UUK simultaneously), the mortality and acute morbidity rates were reduced significantly as compared to TBE single infections. 5. Some of the mixed infections tended to result in chronic disease among the survivors.


Corrigendum: A systematic review and meta-analysis of interventions to decrease cyberbullying perpetration and victimization: an in-depth analysis within the Asia Pacific region.
[This corrects the article DOI: 10.3389/fpsyt.2023.1014258.].


Migraine and stroke.
An association between migraine and ischemic stroke has been observed for many years but exact mechanisms by which migraine can lead to stroke are currently still under investigation. Migraine is related to stroke in several ways. First, ischemic stroke can develop as a complication of an attack of migraine with aura (so called migraineous infarction). Second, epidemiological studies suggest that migraine with aura is a risk factor for ischemic stroke. Third, a patent foramen ovale (PFO) is a well known risk factor for stroke and on the other hand, seems to be associated with migraine with aura. The purpose of this review is to summarize the current literature linking the two neurological diseases: migraine and stroke. For many years, migraine and cerebral ischemic stroke have been linked together. The association between these two diseases is multidimensional and rather complex.


'We couldn't do this without the bursary'.
Our reporter Hannah Flynn sought out nurses' views at the 'save the bursary' lobby in London last week….


Detection of γH2AX foci in mouse normal brain and brain tumor after boron neutron capture therapy.
In this study, we investigated γH2AX foci as markers of DSBs in normal brain and brain tumor tissue in mouse after BNCT. Boron neutron capture therapy (BNCT) is a particle radiation therapy in combination of thermal neutron irradiation and boron compound that specifically accumulates in the tumor. (10)B captures neutrons and produces an alpha ((4)He) particle and a recoiled lithium nucleus ((7)Li). These particles have the characteristics of extremely high linear energy transfer (LET) radiation and therefore have marked biological effects. High LET radiation causes severe DNA damage, DNA DSBs. As the high LET radiation induces complex DNA double strand breaks (DSBs), large proportions of DSBs are considered to remain unrepaired in comparison with exposure to sparsely ionizing radiation. We analyzed the number of γH2AX foci by immunohistochemistry 30 min or 24 h after neutron irradiation. In both normal brain and brain tumor, γH2AX foci induced by (10)B(n,α)(7)Li reaction remained 24 h after neutron beam irradiation. In contrast, γH2AX foci produced by γ-ray irradiation at contaminated dose in BNCT disappeared 24 h after irradiation in these tissues. DSBs produced by (10)B(n,α)(7)Li reaction are supposed to be too complex to repair for cells in normal brain and brain tumor tissue within 24 h. These DSBs would be more difficult to repair than those by γ-ray. Excellent anti-tumor effect of BNCT may result from these unrepaired DSBs induced by (10)B(n,α)(7)Li reaction.


A case of subependymal giant cell astrocytoma without tuberous sclerosis complex and review of the literature.
Subependymal giant cell astrocytoma (SEGA) is a World Health Organization (WHO) grade I tumor most commonly seen in the context of the underlying tuberous sclerosis complex (TSC). SEGA in the absence of TSC is exceedingly rare. We report the youngest known case of SEGA in the absence of genetic or phenotypic evidence of TSC with a 10-year follow-up. We discuss the literature surrounding isolated SEGA including an approach to diagnosis, management, and prognosis.


PD-L1-negative non-small cell lung cancer harbouring a rare BRAF mutation with successful treatment of first-line pembrolizumab plus chemotherapy: A case report and review the literature.
BRAF mutations are uncommon in non-small cell lung cancer (NSCLC), accounting for less than 5% of all NSCLC cases. The utilization of targeted therapies in non-V600E BRAF mutant NSCLC is considered controversial, although non-V600E genotype is reported in ~50% of all BRAF mutant patients. We document the case of a 63-year-old patient with NSCLC harbouring a rare BRAF E501Q mutation, who had prolonged response to immunotherapy combined with chemotherapy in Vietnam. The patient was diagnosed with metastatic PD-L1-negative lung adenocarcinoma and received pembrolizumab plus chemotherapy as first-line treatment. After completing 35 cycles of pembrolizumab and pemetrexed, his disease has remained stable during the treatment-free follow-up period, and he is alive 38 months after treatment initiation at the latest follow-up. Immune-based therapy is an appropriate option for lung adenocarcinoma with rare non-V600E BRAF mutation. Further clinical studies are necessary to determine the effectiveness of using immune-based therapy in this specific population.


Neurotensin analogs indications for use as potential antipsychotic compounds.
This review will be an update, focusing on the central nervous system (CNS) roles of the neurotransmitter, neurotensin. We will provide a summary of current knowledge about neurotensin, why it is an important peptide to study, and where the field is heading. Special emphasis is placed on the development of neurotensin analogs, which has been a major effort of our group, the potential role of neurotensin in Parkinson's disease, and the interaction of neurotensin with other neurotransmitters as evidenced by microdialysis studies.


Antibiotic effects on phagocyte chemiluminescence in vitro.
Phagocytes are an essential defence against infection. Since drugs which affect their function may alter the outcome of infections, we have studied the effect of nine antibiotics on phagocyte function in vitro. The effects of antibiotics on the respiratory burst function of phagocytes from healthy adult donors were investigated using lucigenin-enhanced chemiluminescence in response to serum-opsonised zymosan. Aminoglycosides showed dose-dependent suppression of polymorphonuclear leucocyte chemiluminescence, except streptomycin which caused enhancement. Erythromycin caused profound suppression of chemiluminescence from both polymorphonuclear leucocytes and monocytes. Benzylpenicillin and the cephalosporins caused variable suppression of phagocyte chemiluminescence: cefotaxime increased monocyte chemiluminescence in some experiments. None of the drugs produced suppression at clinically relevant plasma concentrations, but erythromycin and some other drugs are preferentially concentrated in phagocytes to levels which suppress their oxidative metabolism in vitro. It is therefore possible that some antibiotics alter phagocyte function: ex vivo studies of phagocyte function in patients taking antibiotics would be valuable.


Subjective quality of life of community living Sudanese psychiatric patients: comparison with family caregivers' impressions and control group.
Researchers have paid scant attention to comparative studies of quality of life (QOL) issues among psychiatric diagnostic groups; the studies of patient-caregiver concordance ratings had small sample sizes; and the reports are rare from the African and Arab worlds. to assess the subjective QOL of stable Sudanese outpatients, using the WHOQOL-Bref, compared with a general population sample; examine the caregiver-patient concordance; and assess the variables that impact on domains of QOL. The responses of outpatients with schizophrenia (99), major affective disorders (120) and neuroses (81) (mean age 33.8) were compared with 211 controls and the impression of their family caregivers. Patients were dissatisfied with life circumstances; the schizophrenia group and those with co-morbidity had significantly lower QOL scores; while the control group had higher QOL scores. There was no significant impact on QOL domains, of socio-demographic factors, duration of illness and treatment side effects. The schizophrenia group had least concordance with caregivers, but eight items were judged to be satisfactorily concordant for all groups. Psychiatric patients in stable condition can make reliable judgments of QOL, with relatives providing additional information. Differences in QOL and concordance of ratings reflect disease severity.


Methotrexate does not affect ovarian reserve or subsequent assisted reproductive technology outcomes.
The purpose of this research was to study whether methotrexate (MTX) as treatment for ectopic pregnancy (EP) impacts the future fertility of women undergoing assisted reproductive technology (ART) METHODS: In a systematic review and multi-center retrospective cohort from four academic and private fertility centers, 214 women underwent an ART cycle before and after receiving MTX as treatment for an EP. Measures of ovarian reserve and responsiveness and rates of clinical pregnancy (CP) and live birth (LB) were compared in the ART cycles prior and subsequent to MTX. Seven studies were identified in the systematic review, and primary data from four institutions was included in the final analysis. Women were significantly older in post-MTX cycles (35.3 vs 34.7 years). There were no differences in follicle stimulating hormone, antral follicle count, duration of stimulation, oocytes retrieved, or fertilization rate between pre- and post-MTX cycles. However, post-MTX cycles received a significantly higher total dose of gonadotropins (4206 vs 3961 IU). Overall, 42 % of women achieved a CP and 35 % achieved a LB in the post-MTX ART cycle, which is similar to national statistics. Although no factors were identified that were predictive of LB in young women, the number of oocytes retrieved in the previous ART cycle and current AFC were predictive of LB (AUC 0.76, 0.75) for the older women. MTX does not influence ovarian reserve, response to gonadotropin stimulation, and CP or LB rate after ART. MTX remains a safe and effective treatment option for women with asymptomatic EPs.


Plasmafiltration as an effective method in the removal of circulating pegylated liposomal doxorubicin (PLD) and the reduction of mucocutaneous toxicity during the treatment of advanced platinum-resistant ovarian cancer.
The present study evaluates the safety and efficacy of double-plasma filtration (PF) to remove the exceeding pegylated liposomal doxorubicin (PLD) in circulation, thus reducing mucocutaneous toxicity. A total of 16 patients with platinum-resistant ovarian cancer were treated with 50 mg/m2 PLD applied in 1-h IV infusion every 28 days. PF was scheduled at 44-46 h post-infusion. The concentration of plasma PLD and non-liposomal doxorubicin (NLD) was monitored with high-performance liquid chromatography at 116 h post-infusion. A non-linear method for mixed-effects was used in the population pharmacokinetic model. The dose fraction of PLD eliminated by the patient prior to PF was compared with the fraction removed by PF. PLD-related toxicity was recorded according to CTCAE v4.0 criteria and compared to historical data. Anticancer effects were evaluated according to RECIST 1.1 criteria. The patients received a median of 3 (2-6) chemotherapy cycles. A total of 53 cycles with PF were evaluated, which removed 31% (10) of the dose; on the other hand, the fraction eliminated prior to PF was of 34% (7). Exposure to NLD reached only 10% of exposure to the parent PLD. PLD-related toxicity was low, finding only one case of grade 3 hand-foot syndrome (6.7%) and grade 1 mucositis (6.7%). Other adverse effects were also mild (grade 1-2). PF-related adverse effects were low (7%). Median progression-free survival (PFS) and overall survival (OS) was of 3.6 (1.5-8.1) and 7.5 (1.7-26.7) months, respectively. Furthermore, 33% of the patients achieved stable disease (SD), whereas that 67% progressed. PF can be considered as safe and effective for the extracorporeal removal of PLD, resulting in a lower incidence of mucocutaneous toxicity.


Anxiety, depression, and quality of life in postoperative non-small cell lung cancer patients under the intervention of cognitive-behavioral stress management.
Cognitive-behavioral stress management (CBSM) is a psychotherapy that helps patients cognize and manage stress to improve mental health and quality of life. This study aimed to explore the influence of CBSM on anxiety, depression, and quality of life in non-small cell lung cancer (NSCLC) patients. In total, 172 NSCLC patients who received tumor resection were randomized 1:1 into the usual care (UC) group (N = 86) and CBSM group (N = 86) to receive 10-week UC and CBSM interventions. Moreover, all participants attended a 6-month follow-up. Hospital Anxiety and Depression Scales (HADS)-anxiety score at 3rd month (M3) (P = 0.015) and 6th month (M6) (P = 0.018), HADS-depression score at M3 (P = 0.040) and M6 (P = 0.028), and depression rate at M6 (P = 0.035) were descended in CBSM group compared to UC group. Besides, depression severity was reduced at M6 (P = 0.041) in CBSM group compared to UC group, but anxiety severity only showed a decreased trend (P = 0.051). Additionally, Quality of Life Questionnaire-Core 30 (QLQ-C30) global health status score and QLQ-C30 function score at 1st month (M1), M3, and M6 were elevated (all P < 0.05), while QLQ-C30 symptoms score was declined at M1 (P = 0.031) and M3 (P = 0.014) in CBSM group compared to UC group. Notably, the efficacy of CBSM was impressive in patients with baseline depression or undergoing adjuvant therapy. CBSM is a feasible intervention that effectively improves mental health and quality of life in postoperative NSCLC patients.


Latent structure of cognitive tests is invariant in men and women with schizophrenia.
Studies comparing the cognitive functioning of men and women with schizophrenia have produced conflicting results which could arise from sex-based differences in the latent structure of cognitive abilities. The current study used multigroup confirmatory factor analysis to examine invariance in latent structure of cognitive abilities to between men and women with schizophrenia. Confirmatory factor analysis of an initial neurocognitive assessment (men n = 612, women n = 201) and cross-validation using second assessment (men n = 549, women n = 198) demonstrated that a bifactor seven-factor model fit the data best for both men and women. Invariance analyses further indicated this model was invariant across men and women at both assessments. Group comparisons indicated women had significantly higher scores for Semantic Memory, Verbal Memory, and General Cognitive factors, whereas men exhibited better performance on the Vigilance factor. Results indicate that cognition in SZ is characterized by both a general cognitive factor and specific domains for both men and women. Invariance analysis provides evidence that cognitive differences between men and women do not result from sex-based differences in the latent structure of cognitive abilities. Current results also indicate small but statistically significant neurocognitive differences between men and women with schizophrenia.


Giant thoracic neurofibromatosis type 1 with massive intratumoral haemorrhage: a case report.
A 44-year-old man known to have neurofibromatosis type 1 (NF1) presented with an acute enlargement of a long-standing pedunculated thoracic mass and a 4.5 kg weight gain. He was recently treated with anticoagulation for a newly diagnosed atrial fibrillation. Intratumoral bleed was thus suspected to explain the sudden enlargement. Chest computerised tomography confirmed the presence of a large extrathoracic tumour of soft tissue density compatible with a diagnosis of neurofibromatosis and a recent massive intratumoral haematoma. Perioperative angiography demonstrated remarkable hypervascularity. The treatment plan involved embolisation and surgical resection. The histological specimen confirmed a diagnosis of neurofibromatosis type I without malignant transformation. Neurofibromatosis associated with an intratumoral haemorrhage is rare. This is the first scientific report of a massive intratumoral bleed in NF1 subsequent to anticoagulant administration. Anticoagulation should be monitored very closely in neurofibromatosis patients due to their propensity to bleed secondary to the abnormal vascular intima.


Establishing a pharmacy presence in the emergency department: opportunities and challenges in the French setting.
Overview of clinical pharmacy practice around the world shows that pharmaceutical services in emergency departments (EDs) are far less common in Europe than in North America. Reported experiences have shown the impact of a clinical pharmacy service on drug utilisation and safety issues. This commentary presents the implementation of a pharmacy presence in the ED of a French tertiary care hospital. Our experience helps to define the role of the clinical pharmacist in the ED, including patient interviewing, providing medication reconciliation, promoting drug safety, and supporting specific interventions to improve quality of care and patient safety. The role of ED pharmacists in the improvement of quality of care is not necessarily limited to drug therapy, e.g. by helping outpatients to access care and treatment facilities as best suits their needs. Challenges of implementing ED pharmacy services have been identified well, but still require developing strategies to be overcome.


Optic nerve colobomas associated with unilateral focal serous retinal detachment in a dog - In-vivo imaging and outcome following laser retinopexy.
To describe the ophthalmoscopic, in-vivo imaging, fluorescein angiography, and therapeutic photocoagulation outcome in a case of bilateral optic nerve colobomas associated with focal unilateral retinal detachment in a dog. Pretraining eye examination of a 1.6-year-old female German shepherd service dog showed a focal juxta-papillary bullous retinal separation in the right eye. In vivo imaging and angiography were performed under general anesthesia using optical coherence tomography. Nonoverlapping diode laser burns were applied through an operating microscope adapter to selected areas along the leading margins of the detachment. The funduscopic examination and in-vivo imaging revealed bilateral optic nerve colobomas associated with a focal bullous detachment in the right eye. Fluorescein angiography showed absence of blood vessel leakage and absence of staining inside of the retinal elevation. Photocoagulation induced immediate changes in retinal layer reflectivity. Three months post-photocoagulation, the retinal detachment had improved and scarring of the burns was visible. One and two years post-procedure, the retinal detachment resolved. Optical coherence tomography (OCT) imaging provides a detailed analysis of the retinal abnormalities associated with the clinical lesion. Laser retinopexy is a valid therapeutic option to limit the extension of the detachment.


Distribution of cytochromes P-450, cytochrome b5, and NADPH-cytochrome P-450 reductase in an entire human liver.
In rat liver there appear to be significant differences between lobes in the concentration of individual cytochrome P-450 isozymes (Sumner and Lodola, Biochem Pharmacol 36: 391-393, 1987). Because studies in patients often rely on small pieces of liver obtained from diverse anatomical locations, it seemed important to determine if the cytochromes P-450 were also heterogeneously distributed in human liver. Accordingly, tissue was obtained from ten different locations in a single human liver including those most commonly biopsied by percutaneous needles, and by surgeons during laparotomy. The differences observed between locations in the microsomal concentrations of carbon monoxide-binding protein (total cytochrome P-450), cytochrome b5, and NADPH-cytochrome P-450 reductase appeared to be small and were not statistically significant. Likewise, no significant differences were observed between locations in the specific content of HLp, HLp3, HLj, HLx or P450MP. However, the specific concentrations of HLd varied almost 2-fold between the microsomes and this was statistically significant in some cases (P less than 0.05). Our results suggest that, in human livers, regional differences in the content of cytochromes P-450 are generally small but may be significant for some isozymes. With the exception of HLd, tissue obtained by percutaneous or surgical liver biopsies is probably representative of the entire organ with regard to the enzymes assayed.


The new on-line Czech Food Composition Database.
The new on-line Czech Food Composition Database (FCDB) was launched on http://www.czfcdb.cz in December 2010 as a main freely available channel for dissemination of Czech food composition data. The application is based on a complied FCDB documented according to the EuroFIR standardised procedure for full value documentation and indexing of foods by the LanguaL™ Thesaurus. A content management system was implemented for administration of the website and performing data export (comma-separated values or EuroFIR XML transport package formats) by a compiler. Reference/s are provided for each published value with linking to available freely accessible on-line sources of data (e.g. full texts, EuroFIR Document Repository, on-line national FCDBs). LanguaL™ codes are displayed within each food record as searchable keywords of the database. A photo (or a photo gallery) is used as a visual descriptor of a food item. The application is searchable on foods, components, food groups, alphabet and a multi-field advanced search.


Reliability and validity of the incremental shuttle walking test in individuals after stroke.
There are limitations to perform the cardiopulmonary exercise test (CPET) and the six-minute walking test (6MWT) in clinical settings. The incremental shuttle walking test (ISWT) might be an alternative assessment of exercise capacity and an estimation of cardiopulmonary fitness after stroke. To investigate the test-retest and inter-rater reliabilities, the standard error of measurement (SEM) and the minimal detectable change (MDC) of the ISWT, its construct validity to assess exercise capacity and its concurrent validity to estimate cardiopulmonary fitness after stroke. Prospective diagnostic accuracy study. Fifty-one individuals (54 ± 11 years) at the chronic phase (65 ± 73 months after stroke) were included. The distance walked, in meters, during the 12-stage-ISWT and the 6MWT and the peak oxygen uptake (VO2peak, ml.kg-1.min-1) in the CPET (gold standard) were assessed. Significant and high to very high magnitude test-retest and inter-rater reliabilities (0.88≤ICC≤0.93) of the ISWT was found. The SEM for both reliabilities was small (-23.35 m≤ SEM≤41.47 m). The MDC for test-retest and inter-rater reliabilities were 114.63 m and 64.53 m, respectively. For construct validity, a significant and high magnitude correlation between the ISWT and the 6MWT was found (ICC = 0.82). For the concurrent validity, a significant, but low magnitude correlation was found between the ISWT and the VO2peak (rho = 0.42). The ISWT demonstrated adequate reliabilities and construct validity for exercise capacity assessment. However, the concurrent validity of the ISWT as an estimation of cardiopulmonary fitness still requires further research.


Chronic problems in rehabilitation of patients with Laennec's cirrhosis.
Hepatic encephalopathy and ascites are two major complications occuring in patients with Laennec's cirrhosis. Both may be intractable to treatment and may have poor prognoses. Many psychosocial problems are present, and counseling should be geared to optimizing maximum adaptation to the alterations that have resulted. Family and significant others are important support systems for the patient and should be included in as much of the nursing and medical care as possible. The nurse is responsible for a myriad of activities in providing care for cirrhotic patients who develop these chronic problems. Background knowledge regarding nursing theory, pharmacology, pathophysiology, psychology, sociology, and principles of teaching is imperative for effective intervention in these patient care situations.


Variability associated with mandibular buccal shelf area width and height in subjects with different growth pattern, sex, and growth status.
The primary objective of the study was to quantitatively analyze the width and height of the mandibular buccal shelf area (MBS) at 3 different potential locations for mini-implant placement. In addition, we aimed to compare and contrast the bone parameters of the MBS to study the correlation between different growth status (growing or nongrowing), facial types (hypodivergent, normodivergent, and hyperdivergent), and sex differences (male or female). In this retrospective cone-beam computed tomography study, 678 subjects were included. They were divided into groups according to growth status, facial type, and sex. Scans were imported into the reconstruction program and were aligned in 3 different steps. Measurements were made at 6 different coronal sections: mandibular first molar distal root, second molar mesial root, and second molar distal root (bilaterally). The roots of mandibular molars were used as a reference to measure the width and the roof of the inferior alveolar canal to measure the height of the buccal shelf area. Intraobserver reliability was assessed by measuring the width and height of MBS in 20 randomly selected subjects. No significant difference (P > 0.05) was found in the width of MBS between males and females. MBS width increased, and height decreased (P < 0.0001) as moved distally from the first molar distal root to the second molar distal root in all 3 facial types irrespective of age or sex. The hypodivergent facial type had significantly greater bone width than the hyperdivergent facial type at all the 3 locations in both males and females. The hypodivergent facial type had significantly less (P < 0.0001) bone height than the hyperdivergent group at all the 3 locations irrespective of age or sex. The optimal site for MBS mini-implant is the buccal region of the distal root of mandibular second molars. Hypodivergent patients have more width and less height of MBS compared with hyperdivergent patients. MBS mini-implants are not advised for growing patients because of proximity to developing roots.


Playback of female rat ultrasonic vocalizations during sexual behavior.
Both male and female rats emit ultrasonic vocalizations during mating. In an earlier study, female vocalizations were shown to be associated with female darting: when the female was devocalized, she increased her rate of darting. In a preliminary playback study, tape-recorded female ultrasounds were presented to devocalized females paired with intact males. Darting was reduced towards presurgical control levels. In this study, the playback experiment was replicated using a refined procedure to present female ultrasounds to the mating rats. Taped vocalizations were obtained from females, and were presented in a manner which more closely approximated the patterning of ultrasound production seen in the intact female. Each rat pair was tested three times: once prior to the devocalization of the female, and twice afterwards. In one postsurgical test, taped ultrasounds were presented during mating; in the other, tape hiss was presented. Several patterns of behavior increased in frequency when the female was devocalized relative to the control condition, but decreased when tape recorded ultrasounds were presented. These patterns included female darting and approaches towards the partner by both males and females. The darting results confirm and extend the findings of our earlier paper. Changes in approach behavior were not observed previously because the male was confined in the earlier study. This study contains the first direct evidence that female vocalizations affect the socio-sexual behavior of the male.


Sonographic features of mucus-producing carcinoma of the gallbladder.
Few cases of mucus-producing carcinoma of the gallbladder have been reported; accordingly, sonographic features of this entity have not been well described. We discuss two cases of gallbladder carcinoma with marked secretion of mucus that we followed using ultrasound. Acute cholecystitis in these cases resulted from obstruction of the cystic duct by the copious secretion of mucus. Ultrasonography revealed debris-like echoes floating in the lumen of the gallbladder with buoyant migration. Mucus appeared as highly echoic smoke-like or cloud-like masses. Color flow imaging showed no vascularity. The mucus echoes disappeared spontaneously between attacks of cholecystitis. A surgical specimen showed a tumor associated with abundant mucous in the gallbladder. We conclude that mucus-producing carcinoma of the gallbladder should be considered when numerous smoke-like echoes appear in the gallbladder. An accurate diagnosis can be obtained by careful observation using ultrasonography.


Structural implication for the impaired binding of W150A mutant LOX-1 to oxidized low density lipoprotein, OxLDL.
Lectin-like oxidized lipoprotein (OxLDL) receptor 1, LOX-1, is the major OxLDL receptor expressed on vascular endothelial cells. We have previously reported the ligand-recognition mode of LOX-1 based on the crystal structure of the ligand binding domain (C-type lectin-like domain, CTLD) and surface plasmon resonance analysis, which suggested that the functional significance of the CTLD dimer (the 'canonical' dimer) is to harbor the characteristic "basic spine" on its surface. In this study, we have identified the key inter-domain interactions in retaining the canonical CTLD dimer by X-ray structural analysis of the inactive mutant W150A CTLD. The canonical CTLD dimer forms through tight hydrophobic interactions, in which W150 engages in a lock-and-key manner and represents the main interaction. The loss of the Trp ring by mutation to Ala prevents the formation of the canonical dimer, as elucidated from docking calculations using the crystal structure of W150A CTLD. The results emphasize that the canonically formed CTLD dimer is essential for LOX-1 to bind to OxLDL, which supports our proposed view that the basic spine surface present in the correctly formed dimer plays a primal role in OxLDL recognition. This concept provides insight into the pathogenic pattern recognized by LOX-1 as a member of the pattern recognition receptors.


Stress Shielding of Ligaments Using Nonabsorbable Suture Augmentation May Influence the Biology of Ligament Healing.
Nonabsorbable suture augmentation of ligament reconstruction has seen an increase in use over the past several years with the goal of protecting the newly reconstructed ligament while allowing early rehabilitation for a potential earlier return to activity and sport. By spanning the joint with a durable nonabsorbable suture, this construct shares the stress and load seen by the reconstructed ligament, thereby protecting it from forces that could result in an early failure during the early ligamentization phase of the tendon graft. However, stress shielding of the ligament via nonabsorbable suture augmentation is also a double-edged sword, as a reduction in the stress and load seen by the ligament during this healing phase may ultimately have an impact on the final strength and composition of the reconstructed ligament. Although the long-term effects of this stress shielding have yet to be studied or reported in human subjects, multiple biomechanical and animal studies have demonstrated overall changes in architecture, tensile strength, and mechanical properties of a stress-shielded autograft ligament reconstruction.


Agreements between indirect calorimetry and prediction equations of resting energy expenditure in end-stage renal disease patients on continuous ambulatory peritoneal dialysis.
Equations are frequently used to estimate resting energy expenditure (REE) in a clinical setting. However, few studies have examined their accuracy in end-stage renal disease (ESRD) patients. To investigate agreement between indirect calorimetry and several REE estimating equations in 38 ESRD patients on peritoneal dialysis, we performed indirect calorimetry and compared the results with REEs estimated using 5 equations [Harris-Benedict (HBE), Mifflin, WHO, Schofield, and Cunningham]. Measured REE was 1393.2+/-238.7 kcal/day. There were no significant differences between measured and estimated REEs except Mifflin (1264.9+/-224.8 kcal/day). Root mean square errors were smallest for HBE, followed by Schofield, Cunningham, and WHO, and largest for Mifflin (171.3, 171.9, 174.6, 175.3, and 224.6, respectively). In Bland-Altman plot, correlation coefficients between mean values and differences were significant for HBE (r=0.412, p=0.012) and tended to be significant for Cunningham (r=0.283, p=0.086). In DM patients and patients with overhydration, HBE showed significant underestimation when REE increased. In ESRD patients on continuous ambulatory peritoneal dialysis (CAPD), REE-estimating equations have no significant differences from indirect calorimetry, except Mifflin. However, HBE showed greater bias than others when REE was high.


Estimation of bladder contractility from intravesical pressure-volume measurements.
To describe parameters from urodynamic pressure recordings that describe urinary bladder contractility through the use of principles of muscle mechanics. Subtracted detrusor pressure and voided flow were recorded from patients undergoing filling cystometry. The isovolumetric increase of detrusor pressure, P, of a voluntary bladder contraction before voiding was used to generate a plot of (dP/dt)/P versus P. Extrapolation of the plot to the y-axis and the x-axis generated a contractility parameter, vCE (the maximum rate of pressure development) and the maximum isovolumetric pressure, P0 , respectively. Similar curves were obtained in ex vivo pig bladders with different concentrations of the inotropic agent carbachol and shown in a supplement. Values of vCE , but not P0 , diminished with age in female subjects. vCE was most significantly associated with the 20-80% duration of isovolumetric contraction t20-80 ; and a weaker association with maximum flow rate and BCI in women. P0 was not associated with any urodynamic variable in women, but in men was with t20-80 and isovolumetric pressure indices. The rate of isovolumetric subtracted detrusor pressure (t20-80 ) increase shows a very significant association with indices of bladder contractility as derived from a derived force-velocity curve. We propose that t20-80 is a detrusor contractility parameter (DCP). Neurourol. Urodynam. 36:1009-1014, 2017. © 2016 Wiley Periodicals, Inc.


The necessity of using tenaculum for endometrial sampling procedure with pipelle: a randomized controlled study.
To evaluate the use of tenaculum on pain perception of patients and on ease of endometrial sampling procedure with a pipelle. A randomized controlled trial was conducted in 118 patients for assessing pain perception and the ease of the procedure. Patients were randomly assigned to group 1 (without tenaculum) and group 2 (with tenaculum). Visual analog scale (VAS) was used to assess patients' pain at four different times during the process. VAS-3 reflected the pain during the procedure. Likert scale was employed by the surgeon to measure the ease of the procedure. Main outcome was VAS and the secondary outcomes were Likert scale and success rate in obtaining adequate samples of endometrial tissue for histopathological diagnosis. Endometrial sampling procedure could not be performed only on three patients who belonged to group 1. The VAS-3 scores were higher in group 2 than group 1 (p = 0.001). Nullipar patients had higher VAS-3 scores than multipars (p = 0.012). VAS-3 did not vary in pre-peri-postmenopausal women (p = 0.901). Likert scale was lower in postmenopausal women than peri- or pre-menopausal patients (p = 0.020, 0.017, respectively). Use of tenaculum was found by logistic regression analysis to be an independent risk factor for patients' pain perception (p = 0.0001, RR 31.8, 95 % CI 8.3-122.4). Inadequate endometrial sampling was reported in 12 patients who were all postmenopausal. Endometrial sampling procedure without tenaculum is feasible and yields less pain perception than with tenaculum.


Insights into self-healing behavior and mechanism of dicalcium phosphate dihydrate coating on biomedical Mg.
Self-healing coatings have been developed as smart surface coatings for Mg and its alloys to retain local corrosion from the coating damages. In this study, we prepared dicalcium phosphate dihydrate (DCPD) coating on biomedical Mg, and found that the artificial scratches in DCPD coating can be efficiently sealed by anti-corrosive products in both Hank's and normal saline (NS) solutions. Besides, the in-depth study revealed that DCPD was served as not only a physical barrier but also a self-healing agent, demonstrating an autonomous self-healing coating without embedded extra corrosion inhibitors. Moreover, Hank's solution provided foreign-aid film-forming ions to promote self-healing behavior. The findings might offer new opportunities for further studies and applications of efficient self-healing coatings on biodegradable Mg implants.


Adverse effects of intravenous immunoglobulin.
The range of diseases in which intravenous immunoglobulin (IVIG) is effective has expanded significantly since its initial use in primary antibody deficiency. There are at present at least 17 preparations of IVIG in use worldwide with similar profiles of adverse effects. Infusion-related effects range in severity. Mild adverse reactions (headache, flushing, low backache, nausea, wheezing) are often associated with a fast infusion rate, and respond rapidly on slowing the infusion. Very rare episodes of life-threatening anaphylaxis may occur, particularly in those IgA-deficient patients with anti-IgA antibodies; such patients should receive an IgA-depleted preparation of IVIG. There are concerns with any blood product about safety in regard to viral transmission. The 4 outbreaks of non-A non-B hepatitis (probably hepatitis C) in the 1980s were associated with the use of particular batches of IVIG. The more recent exclusion of all anti-hepatitis C virus positive individuals from the donor pool, and the introduction of specific antiviral steps in the manufacture of IVIGs, should prevent further outbreaks. The human immunodeficiency virus (HIV) is effectively inactivated during the manufacturing process itself and HIV transmission has not been reported with IVIG. Rarely, haematological (Coombs' test positive haemolysis), neurological (aseptic meningitis) or renal (transient rises in serum creatinine) adverse effects may be seen when high doses of IVIG are used for immunomodulatory purposes. Haemolysis, due to passive transmission of blood group antibodies (anti-A, anti-D), may be prevented by selecting IVIG batches that give a negative cross-match between the recipient's red cells and IVIG.(ABSTRACT TRUNCATED AT 250 WORDS)


Complications in leg lengthening using an Ilizarov external fixator and intramedullary alignment in children: comparative study during a fourteen-year period.
The purpose of this retrospective study was to evaluate the complications associated with leg lengthening in children treated with the Ilizarov external fixator (IEF) and compare them between two groups of patients: one group was treated using an IEF alone and the other group was treated using an IEF in association with intramedullary alignment (IA). The study was performed at the University Children's Hospital in Belgrade, Serbia during a fourteen-year period (from 2000 to 2014). Complications occurred in 73 paediatric patients who underwent the leg lengthening procedure. Complications were classified according to the Caton classification and compared between two groups. Group I comprised 39 patients who underwent the limb lengthening procedure using IEF alone. Group II consisted of 34 patients who were treated with the combination of IEF and IA using two Kirschner wires (K-wires) or Titanium Elastic Nails (TEN). The duration of hospital treatment was also compared between the two groups and the impact of the type of IA on the occurrence of complications was assessed. There was a high rate of complications in patients treated using an IEF compared with those treated using the combination of IEF and IA, but there was no statistically significant difference between the two groups. There was a statistically significant difference in the duration of initial hospitalisation between the two groups, particularly when comparing TEN usage in IA. A comparison of the group of patients treated using an IEF in association with K-wires and patients treated using IEF and TEN showed there was no statistically significant difference in complication rate and duration of initial hospitalisation. IA has multiple advantages as a method of treatment of leg length inequality. The major effect of applying IA in association with a circular IEF is significantly reduced complication rate and duration of initial hospitalisation, particularly when using TEN as a method of IA. This method of treatment also decreases hospital costs.


Isoform-specific interaction of HP1 with human TAFII130.
The general transcription factor TFIID facilitates recruitment of the transcription machinery to gene promoters and regulates initiation of transcription by RNA polymerase II. hTAF(II)130, a component of TFIID, interacts with and serves as a coactivator for multiple transcriptional regulatory proteins, including Sp1 and CREB. A yeast two-hybrid screen has identified an interaction between hTAF(II)130 and heterochromatin protein 1 (HP1), a chromatin-associated protein whose function has been implicated in gene silencing. We find that hTAF(II)130 associates with HP1 in an isoform-specific manner: HP1alpha and HP1gamma bind to hTAF(II)130, but not HP1beta. In addition, we show that endogenous hTAF(II)130 and components of TFIID in HeLa nuclear extracts associate with glutathione S-transferase-HP1alpha and -HP1gamma. hTAF(II)130 possesses a pentapeptide HP1-binding motif, and mutation of the hTAF(II)130 HP1 box compromises the interaction of hTAF(II)130 with HP1. We demonstrate that Gal4-HP1 proteins interfere with hTAF(II)130-mediated activation of transcription. Our results suggest that HP1alpha and HP1gamma associate with hTAF(II)130 to mediate repression of transcription, supporting a new model of transcriptional repression involving a specific interaction between a component of TFIID and chromatin.


Cortisol metabolism in vitro--III. Inhibition of microsomal 6 beta-hydroxylase and cytosolic 4-ene-reductase.
The in vitro metabolism of cortisol in human liver fractions is highly complex and variable. Cytosolic metabolism proceeds predominantly via A-ring reduction (to give 3 alpha,5 beta-tetrahydrocortisol; 3 alpha,5 beta-THF), while microsomal incubations generate upto 7 metabolites, including 6 beta-hydroxycortisol (6 beta-OHF), and 6 beta-hydroxycortisone (6 beta-OHE), products of the cytochrome P450 (CYP) 3A subfamily. The aim of the present study was, therefore, to examine two of the main enzymes involved in cortisol metabolism, namely, microsomal 6 beta-hydroxylase and cytosolic 4-ene-reductase. In particular, we wished to assess the substrate specificity of these enzymes and identify compounds with inhibitory potential. Incubations for 30 min containing [3H]cortisol, potential inhibitors, microsomal or cytosolic protein (3 mg), and co-factors were followed by radiometric HPLC analysis. The Km value for 6 beta-OHF and 6 beta-OHE formation was 15.2 +/- 2.1 microM (mean +/- SD; n = 4) and the Vmax value 6.43 +/- 0.45 pmol/min/mg microsomal protein. The most potent inhibitor of cortisol 6 beta-hydroxylase was ketoconazole (Ki = 0.9 +/- 0.4 microM; n = 4), followed by gestodene (Ki = 5.6 +/- 0.6 microM) and cyclosporine (Ki = 6.8 +/- 1.4 microM). Both betamethasone and dexamethasone produced some inhibition (Ki = 31.3 and 54.5 microM, respectively). However, substrates for CYP2C (tolbutamide), CYP2D (quinidine), and CYP1A (theophylline) were essentially non-inhibitory. The Km value for cortisol 4-ene-reductase was 26.5 +/- 11.2 microM (n = 4) and the Vmax value 107.7 +/- 46.0 pmol/min/mg cytosolic protein. The most potent inhibitors were androstendione (Ki = 17.8 +/- 3.3 microM) and gestodene (Ki = 23.8 +/- 3.8 microM). Although both compounds have identical A-rings to cortisol, and undergo reduction, inhibition was non-competitive.


Acute effect of dietary therapy of type IV hyperlipoproteinaemia on the serum and lipoprotein concentrations and relative composition.
In a detailed study the acute effect of diet and hospital admission on the plasma and lipoprotein lipid concentrations and composition was studied in 28 patients with type IV hyperlipoproteinaemia. Within 6 days there were significant falls in the mean serum cholesterol and triglycerides, very low density lipoprotein (VLDL) cholesterol and triglycerides and in high density lipoprotein triglycerides. These changes were accompanied by a significant rise in the mean low density lipoprotein (LDL) cholesterol concentrations. Using multiple regession models highly significant predictions of the change in VLDL triglyceride (R2 = 0.71) and LDL cholesterol (R2 = 0.47) were obtained utilising the pre-treatment lipoprotein levels as independant variables. Since elevated LDL cholesterol concentations are associated with atherosclerotic disease such models may have important therapeutic applications.


Update in alar base reduction in rhinoplasty.
The purpose of this article is to further explore the techniques available for alar base reduction by a recent review in this topic, focusing in the current advances in the field, in a clear and readable format. Among the numerous techniques available, the management of cases with wide nasal base and alar flaring remains limited to three options: cinching sutures to pull in the alae together; or to use alar base excisions that remove tissue from the alar lobule to decrease flare and from inside the nostril to decrease width; and flap advancement. Surgical modification of the nasal base is not a routine part of rhinoplasty and should be performed in a conservative manner to prevent complications like nasal stenosis. Moreover, this maneuver should always be the last one in rhinoplasty, as alar base modifications cannot be properly assessed until all other steps have been carried out. VIDEO ABSTRACT.


Altered resting-state hippocampal functional networks associated with chemotherapy-induced prospective memory impairment in breast cancer survivors.
In this study, we aimed to investigate the intrinsic hippocampal functional connectivity (FC) network and its relationship with prospective memory in patients with breast cancer suffering from chemotherapy-induced cognitive impairment (CICI). Thirty-four breast cancer patients before and after adjuvant chemotherapy (CB and CC, respectively) and 31 age- and education-matched cognitively normal (CN) women were recruited and subjected to a prospective memory task and a resting-state functional magnetic resonance imaging scan. Seed-based functional connectivity analysis was used to compare the hippocampal FC networks between CC and CN groups. Partial correction analysis was used to examine the association between the hippocampal FC network and prospective memory in the CC group. The cancer group that underwent chemotherapy obtained significantly poorer scores than the CN group on mini-mental state examination, verbal fluency test, digit span, and prospective memory examination. Compared to the CN group, CC group showed increased hippocampal connectivity in the frontal and parietal cortex, precuneus, posterior cingulate cortex, and the cerebellum. In addition, the increasing hippocampal FC networks were negatively correlated with prospective memory performance in the CC group. These findings suggest maladaptive hippocampal functioning as a mechanism underlying the impairment of prospective memory in patients experiencing CICI.


Occurrence of organophosphorus flame retardants and plasticizers in wild insects from a former e-waste recycling site in the Guangdong province, South China.
Due to the fast growth of the electronic industry, a large quantity of electronic waste (e-waste) is generated worldwide and then often inappropriately dismantled and disposed of. In a pilot study, the occurrence of organophosphorus flame retardants and plasticizers (PFRs) was investigated for the first time in several wild insect species collected from a former e-waste recycling site in the Guangdong province, South China. TEHP was the most abundant PFR (average concentration of 5.8 ng/g ww), followed by TPHP (2.5 ng/g ww), TCIPP (2.2 ng/g ww), TCEP (0.8 ng/g ww), EHDPHP and TCP (both 0.1 ng/g ww). Dragonfly nymphs were the most contaminated insects, with total PFR concentrations of 68 ng/g ww, followed by moth adults (26 ng/g ww) and terrestrial stinkbug (17 ng/g ww). The different contamination patterns observed in the analyzed insects could be explained by their different habitats and feeding habits. This study shows that e-waste recycling areas can be an important local source of contamination with PFRs, mainly caused by inadequate recycling activities.


Is failure of tuberosity suture repair in hemi-arthroplasty for fracture mechanical?
Tuberosity suture repair in hemiarthroplasty for fracture carries risk of malunion giving poor results. Is failure mechanical or biochemical? We investigated the mechanical aspect with repetitive loading in cadaveric repairs. Tests were carried out in line with U.K. Human Tissue Authority regulations. A 4-part fracture was created in 8 cadaver shoulders by osteotomizing the tuberosities. A standard hemiarthroplasty implant was cemented in at correct height and retroversion, and standardized repairs applied. Initial firmness of repair was confirmed by attempting to manually displace the tuberosities with a forceps in multiple planes. All pre-stress tests showed 0 mm movement. Repairs were then subjected to cyclical tension on the cuff musculature and simultaneous gleno-humeral motion for 8000 cycles. The tuberosities were reprobed with a forceps to record any movement. Defining repair failure as the ability to manually displace a tuberosity more than 3 mm, every specimen failed: 100% failure (exact 95% confidence interval 65.2-100% due to sample size). Movements of at least 1 cm were commonly observed. The sutures were loose but had never snapped. Sutures were noted to dig into the tendon and cut partially through bone. Collapse of cancellous bony volume led to looseness and migration of the sutures. Suture repair of tuberosities has mechanical weaknesses; failure may be a mechanical phenomenon.


Characterization of the active site, substrate specificity and kinetic properties of acetyl-CoA:arylamine N-acetyltransferase from pigeon liver.
It could be demonstrated that a sulfhydryl group is involved in the catalysis of acetyl-CoA:arylamine N-acetyltransferase from pigeon liver (EC 22.214.171.124). From ping-pong kinetics it was concluded that there is a covalent acetyl-enzyme intermediate. The respective intermediate could be isolated and chemically characterized as a cysteinyl thioester. Electrophoretically homogeneous acetyl-CoA:acylamine N-acetyltransferase from pigeon liver was able to acetylate a broad variety of aromatic and aliphatic amines from different acetyldonors such as acetyl-CoA, p-nitroacetanilide and p-nitrophenylacetate. Apparent Km values were determined for a number of acetyl donors and acetyl acceptors. Additionally, Ki values were evaluated for CoA, 3',5'-ADP and AMP. Correlation studies of basicity of acceptor amines and acetylation rate demonstrated that there is a limit of the pKa value (about pKa = 1) where the covalently-bound acetyl-enzyme intermediate can still be saponified. Testing crude liver homogenates of several animals including turkey, duck, chicken, cow, pig, horse, sheep, carp, trout and herring the outstanding nature of the pigeon liver enzyme in acetylating very weakly basic amines could be demonstrated. It is shown that the enzyme is quite flexible concerning sterically different acceptor amines, because arylamines whose amino group was effected by large o-substituents could be quantitatively acetylated. After enzymatic acetylation of the first amino group, 1,2-phenylendiamine formed the heterocyclic compound 2-methylbenzimidazole by a spontaneous condensation reaction. There is evidence that with distinct amines formation of heterocyclic compounds may also occur in vivo.


Glutamine Assimilation and Feedback Regulation of L-acetyl-N-glutamate Kinase Activity in Chlorella variabilis NC64A Results in Changes in Arginine Pools.
Glutamine is a metabolite of central importance in nitrogen metabolism of microorganisms and plants. The Chlorella PII signaling protein controls, in a glutamine-dependent manner, the key enzyme of the ornithine/arginine biosynthesis pathway, N-acetyl-L-glutamate kinase (NAGK) that leads to arginine formation. We provide evidence that glutamine promotes effective growth of C. variabilis strain NC64A. The present study shows that externally supplied glutamine directly influences the internal pool of arginine in NC64A. Glutamine synthetase (GS) catalyzes the ATP-dependent conversion of glutamate and ammonium to glutamine. The results of this study demonstrate that glutamine acts as a negative effector of GS activity. These data emphasize the importance of glutamine-dependent coupling of metabolism and signaling as components of an efficient pathway allowing the maintenance of metabolic homeostasis and sustaining growth of Chlorella.


Psychosocial issues that face patients with Charcot-Marie-Tooth disease: the role of genetic counseling.
Charcot-Marie-Tooth (CMT) disease is a hereditary debilitating progressive muscular atrophy and sensory neuropathy of the distal extremities. CMT is usually non-life threatening. Signs of the disease usually present in childhood or in young adulthood and the level of disability can be variable within and between families. Research addressing specific psychosocial and emotional issues faced by individuals with CMT is limited. Fourteen adults with a clinical and/or molecular diagnosis of CMT (ages 32--74 years) consented to an audio taped interview. The format of the interview was based around an informal questionnaire to prompt and guide the interviewee to describe their experiences of living with a disabling genetic disorder. The interviews focused on their experiences of first symptoms and diagnosis, their life experience with CMT, their limitations due to disability and the role of genetic counseling. This study identifies and explores life issues that individuals with CMT may face, specifically grief over the loss of independence, emotional pain and stress such as embarrassment and guilt of passing on a gene mutation, impact on quality of life, the impact of wearing orthopedic devices, and fear of progressive disability. Our findings suggest that that there are emotional and psychosocial issues specific to affected individuals at different life stages and genetic counselors need to be aware of these issues in order to provide age appropriate support and advice to individuals affected by CMT.


The immature platelet fraction in hypertensive disease during pregnancy.
The aim of our study was to elucidate the role of IPF in preeclampsia, because the immature platelet fraction (IPF) is available in most emergency departments. A number of parameters have been introduced to diagnose preeclampsia/HELLP syndrome. The defined cutoffs of angiogenic and antiangiogenic parameters, soluble fms-like tyrosine kinase 1 and placental growth factor, have been approved for clinical routine. However, these parameters need complex analysis and are expensive. The data of 69 pregnant women between 20 and 42 weeks of gestation were analyzed in this retrospective monocentric study. 28 of them had preeclampsia, HELLP syndrome or partial HELLP syndrome fitting the Tennessee criteria (study group 1). Furthermore, 41 normotensive pregnant women were included as controls (study group 2). In both groups the IPF was analyzed. In this study, we demonstrated that the values of IPF were significantly higher in patients with hypertensive diseases than in normotensives, but could not distinguish between preeclampsia and HELLP syndrome. The absolute number of immature platelets of women with preeclampsia was significantly higher and those of HELLP syndrome were significantly lower than values of healthy women. The absolute number of immature platelets as well as mature thrombocytes helps to distinguish between HELLP syndrome and preeclampsia. IPF levels are higher in women with hypertensive pregnancy than in normotensive controls. They could be used to diagnose hypertensive diseases in pregnancy. To distinguish between preeclampsia and HELLP syndrome, thrombocytes or the absolute number of immature platelets is needed.


Differential potentiation of early and late components evoked in olfactory cortex by stimulation of cortical association fibers.
The present study examined in detail the development and decay of potentiation induced in vivo by repeated high-frequency stimulation of cortical association fibers (AF) in piriform cortex (PC). Male Long-Evans rats with chronically-implanted stimulating and recording electrodes were administered potentiating AF stimulation (thirty 10-pulse 100-Hz trains) on 8 consecutive days, followed by a ninth administration after an 8-day layoff. The time course of potentiation was monitored by local field potentials evoked in the PC and olfactory bulb (OB) by 0.1 Hz single-pulse AF test stimulation before, during, and following each potentiating treatment. AF test stimulation evoked two distinct components in the PC, an early component (EC) and a late component (LC). High-frequency AF stimulation produced potentiation of each component, but with very different characteristics. EC potentiation consisted of a brief augmentation during each bout of potentiating stimulation that persisted <2 min after the last high-frequency train and showed no cumulative effects following repeated induction across days. In contrast, LC potentiation developed gradually, requiring several daily potentiation treatments to reach maximum amplitude, and decayed more slowly each time it was induced. Furthermore, LC potentiation persisted in latent form for at least 8 days following its apparent decay and could be reinstated by repeated test stimulation that was without effect at the beginning of the experiment. Potentiation in the OB resembled LC potentiation in its characteristics, but with less latent potentiation. These results indicate that the potentiation reported here is distinctly different from the long-term potentiation previously demonstrated in vitro in the PC, and suggest that this potentiation represents an increase in excitability within the cortical association fiber system that can be stored in latent form and retrieved at a later time. These characteristics make this potentiation a suitable candidate for participation in long-term functional changes within olfactory cortex.


Spiroperidol binding sites on mouse lymphoid cells. Effects of ascorbic acid and psychotropic drugs.
Since highly differentiated cells of mammalian immune systems reportedly have binding sites for a variety of neurohumoral agents, we investigated parameters related to possible existence of dopamine receptors on murine lymphoid cells. Using a dopamine antagonist, [3H]spiroperidol, we found evidence for displaceable binding on mouse spleen cells. Total and displaceable (10 microM haloperidol) binding of spiroperidol was markedly enhanced by the absence of ascorbic acid in the incubation medium. Displaceable binding of a dopamine receptor agonist [( 3H]ADTN) could not be found on lymphoid cells either in the presence or absence of ascorbic acid. In the absence of ascorbate, displaceable spiroperidol binding to mouse spleen cells revealed partially saturable, but complex, kinetics and we calculated positive cooperativity at low ligand concentrations.


Former director of RCN Wales Liz Hewett began at Ty Maeth in 1998.
Great story in Nursing Standard about the book Nursing Matters, which delves into the 50th anniversary of the RCN headquarters in Wales, Ty Maeth (features, May 18). However, Liz Hewett began working at the RCN in Wales in 1998 - not in 1988 as stated in the article.


Initial reactions in biosynthesis of teichuronic acid of Micrococcus lysodeikticus cell walls.
The in vitro biosynthesis of teichuronic acid, the cell wall polysaccharide of Micrococcus lysodeikticus, occurs in two stages. In the initial stage, the particulate enzyme fraction utilizes uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) and uridine diphosphate N-acetylmannosaminuronic acid (UDP-ManNAcUA) to form three intermediates. N-Acetylglucosamine is transferred from UDP-GlcNAc to a carrier lipid present in the particulate enzyme fraction to form the first intermediate, GlcNAc carrier lipid. N-Acetylmannosaminuronic acid is then transferred from UDP-ManNAcUA to the GlcNAc carrier lipid to form ManNAcUA-GlcNAc carrier lipid, the second intermediate. Finally, the transfer of an additional N-acetylmannosaminuronic acid residue from UDP-ManNAcUA yields the third intermediate, (ManNAcUA)2-GlcNAc carrier lipid. Reactions involving UDP-ManNAcUA release uridine diphosphate. Concomitant synthesis of peptidoglycan or membrane mannan inhibits the synthesis of the teichuronic acid intermediates, thereby providing indirect evidence that the carrier lipid is undecaprenol monophosphate.


Two novel compound heterozygous mutations in NGLY1as a cause of congenital disorder of deglycosylation: a case presentation.
NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG) is a multisystemic neurodevelopmental disorder in which affected individuals show developmental delay, epilepsy, intellectual disability, abnormal liver function, and poor growth. This study presents a 10-month-old female infant with elevated liver transaminases, developmental delay, epilepsy (subclinical seizures), and constipation who possesses two compound heterozygous mutations in NGLY1. The proband was admitted to the Department of Gastroenterology, Children's Hospital of Soochow University, with elevated liver transaminases. She had a history of intrauterine growth retardation and exhibited elevated transaminases, global developmental delay, seizures and light constipation during early infancy. Whole-exome sequencing (WES) and Sanger sequencing revealed two compound heterozygous mutations in NGLY1 that had been inherited in an autosomal recessive manner from her parents. One was a termination mutation, c.1168C > T (p.R390*), and the other was a missense mutation, c.1156G > T (p.D386Y). NGLY1-CDDG is a rare disorder, with a few dozen cases. The two mutations of this proband has not been previously identified. This study investigated a Chinese proband with NGLY1-CDDG born from healthy parents who was studied using WES and Sanger sequencing to identify the causative mutations. We identified two novel compound heterozygous mutations in NGLY1, c.1168C > T (p.R390*)/c.1156G > T (p.D386Y), which are probably causative of disease.


Acute graft-versus-host disease in a nonhematopoietic stem cell transplantation candidate treated with decitabine followed by granulocyte colony-stimulating factor-primed peripheral blood stem cells infusion: a special entity of the disease?
With a well-developed strategy of acute graft-versus-host disease (aGVHD) prophylaxis, the prognosis of allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients who develop aGVHD has improved considerably. Meanwhile, transfusion-associated GVHD (TA-GVHD) can be fatal. Recent advancements in immune cellular therapy are being adopted in clinical practice, although many concerns including TA-GVHD remain. This report describes a 64-year-old male non-HSCT candidate diagnosed with acute myeloid leukemia who had received decitabine followed by an infusion of granulocyte-colony-stimulating factor-primed peripheral blood stem cells (G-PBSCs) from his daughter, who carried haploidentical human leukocyte antigen. The patient developed aGVHD on the 20th day after infusion. This study is a single case report of a non-HSCT candidate who developed skin aGVHD with mild clinical course after decitabine and G-PBSCs combination. The clinical course, chimerism, and aGVHD pathology studies are detailed. Compared with conventional aGVHD in allo-HSCT recipients and TA-aGVHD, the presentation of this case followed a self-limited clinical course without marrow aplasia or severe progression. However, the patient eventually died of leukemia without a significant graft-versus-leukemia effect. First, the results demonstrate the existence of aGVHD in elderly non-HSCT candidates receiving adoptive cellular immune therapy. Second, aGVHD occurring under these conditions is probably a unique entity of aGVHD compared to TA-aGVHD and the conventional pattern in allo-HSCT recipients with respect to clinical course and prognosis.


Rapid and simple high-performance liquid chromatographic assay for the determination of metformin in human plasma and breast milk.
A rapid and simple high-performance liquid chromatographic (HPLC) assay for the determination of metformin in human plasma and breast milk is described. After proteins were precipitated with acetonitrile, metformin and the internal standard buformin were resolved on a cation-exchange column and detected by UV detection at 236 nm. Standard curves were linear over the concentration range 20.0-4000 microg/l. Intra- and inter-day coefficients of variation were <9.0% and the limit of quantification was around 20 microg/l.


Pathologic Outcomes in Favorable-risk Prostate Cancer: Comparative Analysis of Men Electing Active Surveillance and Immediate Surgery.
It remains unclear whether men selecting active surveillance (AS) are at increased risk of unfavorable longer term outcomes as compared with men who undergo immediate treatment. To compare adverse pathologic outcomes in men with favorable-risk prostate cancer who underwent delayed prostatectomy after surveillance (DPAS) to those who elected immediate prostatectomy (IRP). We conducted a retrospective analysis of a prospective AS registry from 2004 to 2014. From the Johns Hopkins AS program (n = 1298), we identified a subset of men who underwent DPAS (n = 89) and was representative of the entire cohort, not just those that were reclassified to higher risk. These men were compared with men who underwent IRP (n = 3788). We measured adverse pathologic features (primary Gleason pattern ≥ 4, seminal vesicle invasion [SVI], or lymph node [LN] positivity). Multivariable models were adjusted for age, prostate-specific antigen density, and baseline risk classification. Delayed prostatectomy occurred at a median of 2.0 yr (range: 0.6-9.0) after diagnosis. The DPAS and IRP cohorts demonstrated similar proportions of men with primary Gleason pattern ≥ 4 (17% vs 20%; p = 0.11), SVI (3.3% vs 3.2%; p = 0.53), LN positivity (2.3% vs 1.2%; p = 0.37), and overall adverse pathologic features (21.3% vs 17.0%; p = 0.32). The adjusted odds ratio of adverse pathology was 1.33 (95% confidence interval, 0.82-2.79; p = 0.13) for DPAS as compared with IRP. Limitations include a modest cohort size and a limited number of events. In men with favorable-risk cancer, the decision to undergo AS is not independently associated with adverse pathologic outcomes. This report compares men with favorable-risk prostate cancer who elected active surveillance with those who underwent immediate surgery accounting for evidence that approximately one-third of men who choose surveillance will eventually undergo treatment. Our findings suggest that men who are closely followed with surveillance may have similar outcomes to men who elect immediate surgery, but additional research is needed.


Synthesis and biological activity of 21,22-cyclosteroids and their derivatives.
Synthesis of 21,22-cyclosteroids has been achieved starting from pregnenolone acetate. The key transformation was the Kulinkovich reaction of 17-vinyl steroids with esters. The resulting cyclopropanols were further subjected to three-membered ring-opening under various conditions including to base-, palladium or visible light-promoted isomerization and cross-coupling reaction. A number of steroidal Δ2-6-ketones and 3β-hydroxy-Δ5-enes with functional groups at C-21 - C-23 have been synthesized via the 21,22-cyclosteroids. The antiproliferative and antihormonal activity of the obtained compounds on the cell lines of prostate (22Rv1) and breast (MCF-7) cancer was studied. The androgen receptor activity was assessed by reporter assay when the expression of signalling proteins was evaluated by immunoblotting. (20S,22R)-22-Acetoxy-21,22-cyclo-5α-cholest-5-ene with the moderate antiandrogenic potency revealed IC50 values of 18.4 ± 1.2 and 14.6 ± 1.4 µM against MCF-7 and 22Rv1 cells, respectively, and its effects on the expression of AR-V7, cyclin D1 and BCL2 were explored.


Bile acid secretion and pool size during phenobarbital induced hypercholeresis.
An increase in bile flow after phenobarbital administration occurs in the rat and other species; however, the mechanism(s) of the choleretic effect is incompletely understood and the role of the increase in liver weight is controversial. We therefore measured bile flow, bile acid secretion and pool size in male Sprague-Dawley rats pretreated with phenobarbital (75 mg/kg/day) for 6 days; liver weight, liver cell volume and DNA content were also evaluated. Phenobarbital treatment increased liver weight and mean hepatocyte volume by 39 and 26%, respectively, while total DNA content did not change, thus indicating that the hepatomegaly results principally from hypertrophy rather than hyperplasia. Bile flow was significantly higher in treated rats when expressed per unit of body weight (64.6 +/- 2.4 (S.E.) vs 53.3 +/- 1.6 microliter/min/kg; P less than 0.05) but was unchanged when expressed per gram of liver (1.40 +/- 0.04 vs 1.37 +/- 0.06 microliter/min/g; P greater than 0.5). The initial bile acid secretion rate and pool size were both significantly reduced in the phenobarbital group compared to controls (1224.2 +/- 110.4 vs 1656.6 +/- 163.2 nmol/kg/min and 562.8 +/- 41.5 vs 814.3 +/- 78.3 mumol/kg; both P less than 0.05), whereas the basal synthetic rate was unchanged. These findings suggest that the enlarged, phenobarbital-treated hepatocyte produces more bile than the normal cell, despite the decreased secretion of bile acids. Therefore, the drug-induced choleresis involves a selective increase in the bile acid-independent fraction of bile flow.


Non-linear response of colloid monolayers at high-frequency probed by ultrasound-driven microbubble dynamics.
High-frequency interfacial rheology of complex interfaces remains challenging yet it is central to the performance of multiphase soft matter products. We propose to use ultrasound-driven bubble dynamics to probe the high-frequency rheology of a colloid monolayer used as model system with controlled interactions and simultaneous monitoring of the microstructure. We hypothesize that by comparing the response of colloid-coated bubbles with that of a bare bubble under identical experimental conditions, it is possible to detect the non-linear response of the monolayer and use it to extract interfacial rheological properties at 104s-1. Using high-speed video-microscopy, the dynamics of colloid-coated bubbles were probed to study the micromechanical response of the monolayer to high-frequency deformation. Protocols analogous to stress-sweep and frequency-sweep were developed to examine the stress-strain relationships. A simple model, motivated by the observed non-linear responses, was developed to estimate the interfacial viscoelastic parameters. The estimated elastic moduli of colloid monolayers at 104s-1 are about an order of magnitude larger than those measured at 1 s-1. The monolayers exhibit non-linear viscoelasticity for strain amplitudes as small as 1%, and strain-softening behaviour. These findings highlight the applicability of acoustic bubbles as high-frequency interfacial probes.


Coptidis Rhizoma inhibits NLRP3 inflammasome activation and alleviates renal damage in early obesity-related glomerulopathy.
Obese subjects have been considered to be in a state of chronic, low-grade systemic inflammation. Excess fat accumulation and persistent inflammation may promote renal dysfunction, to cause chronic kidney disease (CKD) and even end-stage kidney failure. Coptidis Rhizoma is a classical traditional Chinese herb well known for its hypoglycemic and hypolipidemic properties. The mechanism is partially associated with its anti-inflammatory effect. However, this effect is rarely investigated in obesity and obesity-related glomerulopathy (ORG). The current study was designed to evaluate the effect of Coptidis Rhizoma on ORG. It also aimed to determine whether this renal protection effect of Coptidis Rhizoma was related to the inhibition of NLRP3 inflammasome in ORG. Coptidis Rhizoma concentrated granules were prepared and the main components were identified by 3D-High Performance Liquid Chromatography (3D-HPLC) assay. The animal model of early stage ORG was established in obesity-prone (OP) rats by high protein and high fat diet feeding for 12 weeks. The treatment with Coptidis Rhizoma at different dosages was administered by intragastric infusion simultaneously. Then body weight, kidney weight, plasma lipid profiles, 24 h urine protein/albumin content and kidney histology were measured. Inflammatory biomarkers were examined both in the rat plasma and renal cortex. The gene expressions of NLRP3 inflammasome complex and NF-κB in renal tissues were also measured. Coptidis Rhizoma alleviated dyslipidemia and reduced the renal weight of the rats with ORG. Meanwhile, urinary albumin to creatinine ratio and creatinine clearance rate were significantly improved. Coptidis Rhizoma also attenuated glomerular hypertrophy, mesangial hyperplasia, and effacement of podocyte foot in renal tissues of ORG rats. In addition, Coptidis Rhizoma intervention decreased the levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-18) both in plasma and renal tissue. The gene expression of NLRP3 inflammasome was down-regulated and NF-κB activity was also inhibited by Coptidis Rhizoma in renal tissues of ORG rats. Coptidis Rhizoma can ameliorate early renal damage in ORG rats and the mechanisms appear to be related to the inhibition of NLRP3 inflammasome complex.


Whole genome sequencing reveals hidden transmission of carbapenemase-producing Enterobacterales.
Carbapenemase-producing Enterobacterales (CPE) infection control practices are based on the paradigm that detected carriers in the hospital transmit to other patients who stay in the same ward. The role of plasmid-mediated transmission at population level remains largely unknown. In this retrospective cohort study over 4.7 years involving all multi-disciplinary public hospitals in Singapore, we analysed 779 patients who acquired CPE (1215 CPE isolates) detected by clinical or surveillance cultures. 42.0% met putative clonal transmission criteria, 44.8% met putative plasmid-mediated transmission criteria and 13.2% were unlinked. Only putative clonal transmissions associated with direct ward contact decreased in the second half of the study. Both putative clonal and plasmid-mediated transmission associated with indirect (no temporal overlap in patients' admission period) ward and hospital contact did not decrease during the study period. Indirect ward and hospital contact were identified as independent risk factors associated with clonal transmission. In conclusion, undetected CPE reservoirs continue to evade hospital infection prevention measures. New measures are needed to address plasmid-mediated transmission, which accounted for 50% of CPE dissemination.


Primary erector spinae pyomyositis causing an epidural abscess: case report and literature review.
Primary pyomyositis (PM) is a rare bacterial infection of skeletal muscle usually restricted to tropical zones. Typically caused by Staphylococcus aureus, primary staphylococcal PM associated with an epidural abscess has not been reported before. We present the first case of staphylococcal PM associated with an epidural abscess. Case report. A 56-year-old woman. Clinical follow-up at 9 months. This 56-year-old woman presented with a sudden onset of left lumbar back pain and sciatica without prior illness. She was pyrexial on admission, with elevated inflammatory markers but with no obvious systemic source of sepsis. Spinal magnetic resonance imaging and subsequent surgery revealed an erector spinae abscess causing an epidural abscess via the left L4/5 intervertebral foramen. Both back pain and sciatica were immediately improved postoperatively. Culture revealed S aureus as the sole organism sensitive to flucloxacillin. Intravenous therapy was converted to oral after 12 days once the erythrocyte sedimentation rate had normalized and she was asymptomatic. She remains asymptomatic and without clinical signs at the 9-month follow-up. Spinal infection must always be considered when back pain and sciatica are associated with clinical signs of sepsis. We present the first case of staphylococcal PM associated with an epidural abscess.


Endometrial cultures in acute pelvic inflammatory disease.
The objective of this study was to investigate the correlation of endometrial culture results with the clinical diagnosis of acute pelvic inflammatory disease (PID). A total of 130 patients admitted with the clinical diagnosis of acute PID were prospectively enrolled in this study. Endometrial cultures by transcervical aspirate currette were obtained from all patients. Of 130 patients, 114 were discharged with a clinical diagnosis of PID. Of these 114 patients, 112 had positive endometrial cultures for pathogenic organisms. The correlation between endometrial culture results and the clinical diagnosis of acute PID was 98.2%. When patients with only mycoplasmas in the endometrial cavity were excluded, the correlation between endometrial culture results and the clinical diagnosis of acute PID was 93.8%. These data demonstrate the exceedingly high degree of correlation between endometrial culture results and the clinical diagnosis of acute PID. Therefore, endometrial cultures may serve as a useful adjunct in the evaluation of patients with a clinical diagnosis of acute PID.


Biosensing and environmental sensing for emergency and protection e-Textiles.
The ProeTEX project introduced for the first time a complete set of smart garments integrating sensors for the physiological and environmental monitoring of emergency operators. These "smart" garments have been deeply tested in emergency-like contexts by professional rescuers, in order to assess real-time acquisition, processing and transmission of data from moving subjects while operating in harsh conditions. Here we report an overview of the main results obtained during field trials performed in 2010 by Italian and French professional firefighters, in specialized training centers, while dressing the ProeTEX prototypes. Results clearly demonstrate the benefit and step forward of such a system in order to monitor and coordinate rescuers even during intervention far away from the emergency headquarter.


Preprocessing surface EMG data removes voluntary muscle activity and enhances SPiQE fasciculation analysis.
Fasciculations are a clinical hallmark of amyotrophic lateral sclerosis (ALS). The Surface Potential Quantification Engine (SPiQE) is a novel analytical tool to identify fasciculation potentials from high-density surface electromyography (HDSEMG). This method was accurate on relaxed recordings amidst fluctuating noise levels. To avoid time-consuming manual exclusion of voluntary muscle activity, we developed a method capable of rapidly excluding voluntary potentials and integrating with the established SPiQE pipeline. Six ALS patients, one patient with benign fasciculation syndrome and one patient with multifocal motor neuropathy underwent monthly thirty-minute HDSEMG from biceps and gastrocnemius. In MATLAB, we developed and compared the performance of four Active Voluntary IDentification (AVID) strategies, producing a decision aid for optimal selection. Assessment of 601 one-minute recordings permitted the development of sensitive, specific and screening strategies to exclude voluntary potentials. Exclusion times (0.2-13.1 minutes), processing times (10.7-49.5 seconds) and fasciculation frequencies (27.4-71.1 per minute) for 165 thirty-minute recordings were compared. The overall median fasciculation frequency was 40.5 per minute (10.6-79.4 IQR). We hereby introduce AVID as a flexible, targeted approach to exclude voluntary muscle activity from HDSEMG recordings. Longitudinal quantification of fasciculations in ALS could provide unique insight into motor neuron health.


How staff characteristics influence residential care facility staff's attitude toward person-centered care and informal care.
Staff members, and their attitudes, are crucial for providing person-centered care in residential care facilities for people with dementia. However, the literature on the attitudes of nursing staff regarding person-centered care is limited. The objective of this study is to explore the association between staff characteristics (age, education level, years of work experience and function, i.e., care or welfare) and staff attitudes toward perceived person-centered care provision and including informal caregivers in the caregiving process in residential care facilities. A convenience sample of 68 care staff - nurses and nurse assistants - welfare staff members - activity counselors, hostesses, and living room caretakers - of two residential care facilities filled out a questionnaire. Staff attitudes regarding perceived person-centered care were measured with the Person-centered Care Assessment Tool (P-CAT). Staff attitudes regarding informal care provision were measured with the Attitudes Toward Families Checklist (AFC). Multiple linear regression analysis explored the association between variables age, work experience, education, and function (care or welfare). A higher age of staff was associated with a more negative attitude toward perceived person-centered care and informal care provision. Welfare staff had a more negative attitude toward the inclusion of informal caregivers than care staff. The perceived person-centered care provision of the care and welfare staff was both positive. Work experience and education were not associated with perceived person-centered care provision or informal care provision. This study is one of the first to provide insight into the association between staff characteristics and their attitude toward their perceived person-centered care provision and informal care provision. A higher age of both the care and welfare staff was associated with a more negative attitude toward their perceived person-centered care and informal care provision. Welfare staff had a less positive attitude toward informal care provision. Additionally, future studies, also observational studies and interview studies, are necessary to collect evidence on the reasons for negative attitudes of older staff members towards PCC and informal care giving, to be able to adequately target these reasons by implementing interventions that eliminate or reduce these negative attitudes.


How do medical students view the work life of primary care and specialty physicians?
Student perceptions of day-to-day physician work life, and relationships between these perceptions and specialty choices, have not been quantitatively explored. The study's purposes were to measure student perceptions of primary care and specialist physician work life, including administrative burden, time pressures, autonomy, and relationships with patients, to determine whether senior students' perceptions vary from junior students' perceptions and to determine whether students with primary care career plans view primary care work life differently than their peers. A cross-sectional anonymous survey was offered to all students at three allopathic US medical schools between 2006 and 2008. Of 1,533 eligible students, 983 submitted usable surveys (response rate 64.1%). Students viewed the day-to-day work life of all physicians negatively but viewed primary care physician work life more negatively. Senior students viewed specialist work life more positively and primary care work life more negatively than junior students. Students planning primary care and specialist careers had similar views of primary care and specialist work life. Students have negative views of the work life of all physicians, especially primary care physicians. Students planning careers in primary care share this negative view of their future work life, suggesting that their career choices are not based on different work life perceptions.


Anxiety-like subjective effect of ethanol antagonist RO 15-4513 demonstrated in pentylenetetrazol discrimination.
Ro 15-4513, a benzodiazepine-receptor ligand which antagonizes ethanol, was tested in the pentylenetetrazol discrimination, a bioassay for anxiogenic drugs. Rats were trained with food reward to discriminate pentylenetetrazol (PTZ) from saline in a two-lever operant task. In lever-selection tests, rats selected the PTZ lever both after PTZ and after Ro 15-4513. The PTZ-like stimulus produced by Ro 15-4513 was blocked by diazepam and by the benzodiazepine receptor blocker Ro 15-1788. Substitution for the anxiogenic drug PTZ, and blockade by the anxiolytic diazepam, support the hypothesis that Ro 15-4513 is anxiogenic; blockade by Ro 15-1788 suggests that the PTZ-like stimulus produced by Ro 15-4513 occurs through its action at the benzodiazepine receptor.


Study on the preparation of molecularly imprinted ZrO2-TiO2 photocatalyst and the degradation performance of hydroquinone.
In this paper, molecularly imprinted Zr-doped TiO2 photocatalysts (MIP-ZrO2-TiO2) were prepared by the molecularly imprinted sol-gel method for the photocatalytic degradation study of hydroquinone (HQ) as the target pollutant. For the effectiveness of the MIP-ZrO2-TiO2 catalyst in degrading HQ, the effects of Zr doping ratio, imprinted molecule dosage, calcination conditions, and pollutant concentration on its photocatalytic activity were investigated. XRD, TEM, XPS, and other techniques were used to evaluate the materials, and the findings revealed that MIP-ZrO2-TiO2 films with imprinted HQ were successfully produced on the ZrO2-TiO2 surface. The optimal preparation conditions were n(Ti):n(Zr) = 100:8, m(HQ) = 1.5 g, 550 °C for the calcination temperature, and 2 h for the calcination duration. The optimum reaction conditions were 10 mg/L HQ concentration, 1 g/L catalyst dose, and a pH of 6.91. According to the findings of photocatalytic tests, during 30 min of UV lamp (365 nm) irradiation, the degradation rates of MIP-ZrO2-TiO2, ZrO2-TiO2, and TiO2 for HQ were 90.58%, 83.94%, and 58.30%, respectively. The findings revealed that the doping of Zr metal and the addition of imprinted molecules improved the photocatalytic activity of TiO2, which can be used for the efficient treatment of low concentrations of hard-to-degrade hydroquinone.


The importance of start codon of nosM in nosiheptide production.
The present study was designed to investigate the effects of start codon of nosM on the biosynthesis of nosiheptide. Target genes were amplified by overlap PCR. After homologous recombination to construct engineered strains, nosiheptide production was analyzed by HPLC. Three mutants with different start codon of nosM were constructed, and nosiheptide production of each mutant was analyzed and compared. Replacement of the start codon of nosM significantly decreased the production of nosiheptide. In conclusion, start codon usage could greatly affect the biosynthetic efficiency in the biosynthetic gene cluster of nosiheptide.


Public awareness and practical knowledge regarding Hepatitis A, B, and C: a two-country survey.
To assess the level of public awareness and practical knowledge regarding Hepatitis A, B, and C in two low-endemic countries (Germany and The Netherlands). Two large-scale surveys (N=1989 and 668). Although public awareness was high, practical knowledge regarding differences in the mode of transmission, consequences, and prevention was very low in both countries, especially among those with a lower level of education. Future public health initiatives are warranted to increase knowledge as a first step to empower people, especially those with a lower level of education.


[Myocardial preconditioning with volatile anesthetics. General anesthesia as protective intervention?].
Reduction of the perioperative cardiovascular risk with pharmacological interventions plays a prominent role in routine anesthesia practice. For example, perioperative beta-blockade is well established in anesthesiological treatment of patients. There is a growing body of evidence supporting the cardioprotective effects of volatile anesthetics known as anesthetic-induced preconditioning. There are numerous and complex data from animal studies. The mechanisms of anesthetic-induced preconditioning have been extensively studied but have still not been clearly identified. Initial clinical data show the cardioprotective effects of volatile agents by looking at parameters of myocardial function and laboratory values and therefore, the question of the relevance of these data for routine clinical practice has been raised. This review gives a summary of the currently available data focusing on the mechanisms of anesthesiological preconditioning and clinical studies.


Evaluation of electrocardiogram T-wave dispersion measurement methods.
Methods for measuring the T-wave dispersion are difficult to improve, because the exact result is unknown. This study describes a flexible and cheap method for analysing the measurement problems. The analysis consisted of measuring the T-wave dispersion of electrocardiograms and vector loops with simulated dispersion. The vector loops were simulated using two primary T-waves that were identical, quasi-monophasic and located in orthogonal leads. The dispersion was the time delay between the primary T-waves. The electrocardiograms were projections of the vector loops on approximations to the orientations of leads in the standard 12-lead ECG. This simulation model was validated by matching simulated ECGs and vector loops with measured ECGs and vector loops drawn from a population of 247 patients with acute myocardial infarction. The analysis of the measurement problems was demonstrated by measuring an approximation to the classical QT-dispersion in ECGs with simulated dispersion in the interval 0-100 ms, in steps of 2 ms. This showed that the QT-dispersion was unable to measure the simulated dispersion accurately in the clinically relevant interval of 50-100 ms. The results indicated that the low prognostic accuracy of the QT-dispersion could be due to an inaccurate measurement method.


A Novel Mean-Field-Game-Type Optimal Control for Very Large-Scale Multiagent Systems.
In this article, a decentralized adaptive optimal controller based on the emerging mean-field game (MFG) and self-organizing neural networks (NNs) has been developed for multiagent systems (MASs) with a large population and uncertain dynamics. This design can effectively break the "curse of dimensionality" and reduce the computational complexity by appropriately integrating emerging MFG theory with self-organizing NNs-based reinforcement learning techniques. First, the decentralized optimal control for massive MASs has been formulated into an MFG. To unfold the MFG, the coupled Hamilton-Jacobian-Bellman (HJB) equation and Fokker-Planck-Kolmogorov (FPK) equation needed to be solved simultaneously, which is challenging in real time. Therefore, a novel actor-critic-mass (ACM) structure has been developed along with self-organizing NNs subsequently. In the developed ACM structure, each agent has three NNs, including: 1) mass NN learning the mass MAS's overall behavior via online estimating the solution of the FPK equation; 2) critic NN obtaining the optimal cost function through learning the HJB equation solution along with time; and 3) actor NN estimating the decentralized optimal control by using the critic and mass NNs along with the optimal control theory. To reduce the NNs' computational complexity, a self-organizing NN has been adopted and integrated into a developed ACM structure that can adjust the NNs' architecture based on the NNs' learning performance and the computation cost. Finally, numerical simulation has been provided to demonstrate the effectiveness of the developed schemes.


Studies on the inhibition of rejection of Trichostrongylus colubriformis larvae from immune sheep.
A total of 8 drugs were examined for their ability to suppress the rejection of Trichostrongylus colubriformis infective larvae (L3) from immune sheep. Specific antagonists of leukotrienes (piroxicam), prostaglandin (indomethacin) and the immunosuppressant cyclosporin A were given orally, while injectable preparations of dexamethasone, chlorpheniramine, BN 52051, WEB 2086 (anti-platelet-activating factor) and theophylline were administered as directed. The drugs were given for 5 days prior to and 4 days after challenge with 20,000 L3, when worm counts were done. Corticosteroids inhibited rejection by around 70% in two experiments, and none of the remaining compounds were effective. In the third study, six of the drugs were given to susceptible sheep and did not affect the establishment of a primary infection with T. colubriformis.


Expression of dystrophin-associated glycoproteins during human fetal muscle development: a preliminary immunocytochemical study.
An immunocytochemical study was performed on quadriceps muscle from eight fetuses ranging from 12 weeks of gestation to term, using antibodies against the dystrophin-associated proteins, in order to evaluate the developmental expression of these proteins. For comparison, antibodies against dystrophin and utrophin were also used. The expression of the 59 kDa dystrophin-associated protein was simultaneous with that of dystrophin, which is also a subsarcolemmal protein. The extracellular glycoprotein of 156 kDa (alpha-dystroglycan) and the transmembrane glycoprotein of 43 kDa (beta-dystroglycan) appeared to be expressed later. The transmembrane glycoproteins of 50 kDa (adhalin) and 35 kDa were fully expressed at an even later stage of fetal muscle development. This study suggests that the subsarcolemmal proteins may have an essential role in the assembly of the transmembrane and extracellular components of the dystrophin-glycoprotein complex during fetal muscle development. The knowledge obtained from observing the developmental expression of these proteins may contribute to the understanding of the molecular mechanism of their different involvement in muscle disorders.


Evaluation of a saliva molecular point of care for the detection of SARS-CoV-2 in ambulatory care.
Rapid identification of SARS-CoV-2-infected individuals is a cornerstone for the control of virus spread. The sensitivity of SARS-CoV-2 RNA detection by RT-PCR is similar in saliva and nasopharyngeal swabs. Rapid molecular point-of-care tests in saliva could facilitate, broaden and speed up the diagnosis. We conducted a prospective study in two community COVID-19 screening centers to evaluate the performances of a CE-marked RT-LAMP assay (EasyCoV) designed for the detection of SARS-CoV2 RNA from fresh saliva samples, compared to nasopharyngeal RT-PCR, to saliva RT-PCR and to nasopharyngeal antigen testing. Overall, 117 of the 1718 participants (7%) tested positive with nasopharyngeal RT-PCR. Compared to nasopharyngeal RT-PCR, the sensitivity and specificity of the RT-LAMP assay in saliva were 34% and 97%, respectively. The Ct values of nasopharyngeal RT-PCR were significantly lower in the 40 true positive subjects with saliva RT-LAMP (Ct 25.9) than in the 48 false negative subjects with saliva RT-LAMP (Ct 28.4) (p = 0.028). Considering six alternate criteria for reference tests, including saliva RT-PCR and nasopharyngeal antigen, the sensitivity of saliva RT-LAMP ranged between 27 and 44%. The detection of SARS-CoV-2 in crude saliva samples with an RT-LAMP assay had a lower sensitivity than nasopharyngeal RT-PCR, saliva RT-PCR and nasopharyngeal antigen testing.Registration number: NCT04578509.


Structure elucidation of angiotensin converting enzyme inhibitor L-681,176 from Streptomyces sp. MA 5143a.
L-681,176 (1, C12H23N5O7) is an inhibitor of angiotensin converting enzyme produced by Streptomyces sp. MA 5143a. The structure of L-681,176 has been determined by NMR and mass spectral analysis.


Cytokine responses and epithelial function in the intestinal mucosa.
Inflammatory diseases of mucosal organs are significantly influenced by the microenvironment in which they reside. Cytokines found within this microenvironment contribute significantly to endpoint functions of the mucosa. Studies dating back to the 1990s have revealed that epithelial cells are both a source as well as a target for numerous cytokines and that such signaling can substantially influence the outcome of mucosal disease, such as inflammatory bowel disease. Here, we will review literature regarding intestinal epithelial cells as sources and responders to cytokines found in the intestinal milieu. These studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation.