[Acute lung oedema during a tako-tsubo syndrome associated with mitral stenosis].
The tako-tsubo syndrome is the subject of a lot of publications focusing on the different circumstances of discovery (emotion, anesthetic stress...). We report the original case of a patient of 56 years with a tight mitral stenosis, hospitalized for acute lung oedema, sinus rhythm, in which the original data and follow-up studies have identified a tako-tsubo syndrome with favorable evolution.


An investigation to the prolonged requirement (>7 days) of vasopressors in cervical spinal cord injury patients-a retrospective analysis.
Retrospective chart review. The primary aim was to identify the number of patients requiring vasopressors beyond the first week of cervical spinal cord injury (SCI). Secondary objectives were to note the type, duration and doses of vasopressors and any association between prolonged vasopressors use and outcome. Neurosurgical intensive care of a tertiary trauma care centre. After Ethical approval we retrospectively collected the data of patients of isolated cervical SCI admitted to neurosurgical intensive care from January to December 2017. Vasopressor requirement for sepsis or cardiac arrest was excluded. Out of 80 patients analysed, 54 (67.5%) received vasopressors. The prolonged requirement of vasopressors was observed in 77.7%. Our preferred agent was dopamine (64.8%). We found out that longer requirement (in days) of high dose of dopamine was associated with higher survival (p = 0.03). Our results describe a significant portion of cervical SCI patients need ongoing vasopressor to maintain a mean arterial pressure >65 mm of Hg beyond first week. We observed patients who required longer duration of high dose dopamine had a higher chance of survival suggesting some unknown mechanism of high dose of dopamine. This is first such observation, further studies are needed to substantiate.


Sonographic demonstration of calculi within a urethral diverticulum.
A case in which sonography demonstrated that calculi may arise in female urethral diverticula is presented. The diagnosis of female urethral diverticula is reviewed.


A scoping review of the use of cannabidiol in psychiatric disorders.
Cannabidiol (CBD) has become a fast-growing avenue for research in psychiatry, and clinicians are challenged with understanding the implications of CBD for treating mental health disorders. The goal of this review is to serve as a guide for mental health professionals by providing an overview of CBD and a synthesis the current evidence within major psychiatric disorders. PubMed and PsycINFO were searched for articles containing the terms "cannabidiol" in addition to major psychiatric disorders and symptoms, yielding 2952 articles. Only randomized controlled trials or within-subject studies investigating CBD as a treatment option for psychiatric disorders (N = 16) were included in the review. Studies were reviewed for psychotic disorders (n = 6), anxiety disorders (n = 3), substance use disorders (tobacco n = 3, cannabis n = 2, opioid n = 1), and insomnia (n = 1). There were no published studies that met inclusion criteria for alcohol or stimulant use disorder, PTSD, ADHD, autism spectrum disorder, or mood disorders. Synthesis of the CBD literature indicates it is generally safe and well tolerated. The most promising preliminary findings are related to the use of CBD in psychotic symptoms and anxiety. There is currently not enough high-quality evidence to suggest the clinical use of CBD for any psychiatric disorder.


The right retroperitoneal approach for abdominal aortic surgery.
Retroperitoneal exposure of the abdominal aorta is usually performed through a left flank incision. An alternative approach to the abdominal aorta is described utilizing a right flank incision. Indications for the use of the right retroperitoneal approach during surgery for aortic aneurysms include right renal artery stenosis, right iliac artery aneurysm, need for simultaneous cholecystectomy, multiple or recent intraabdominal procedures, and sigmoid colostomy. A series of 17 patients is presented to illustrate the utility of this approach. There was one operative death in an emergent patient; the cause of death was not related to the method of aortic exposure. The remaining patients recovered quickly. The anatomic advantages and limitations of this exposure are discussed. We believe that retroperitoneal aortic exposure is superior to midline transperitoneal exposure. Aortic exposure utilizing a right retroperitoneal approach is a useful option in the surgical armamentarium.


Platinum Chemotherapy Hypersensitivity: Prevalence and Management.
Hypersensitivity reactions to platinum agents are common. For carboplatin and cisplatin, the first hypersensitivity reaction typically occurs around the second and third re-exposure during the second line of therapy (eighth and ninth courses overall). For oxaliplatin, the first hypersensitivity reaction can occur throughout the treatment course. Skin testing helps risk stratify patients to appropriate desensitization protocols and assess risk for breakthrough HSRs during desensitization. A risk-stratification protocol using 3 serial skin tests and desensitization protocols enables patients with platinum agent hypersensitivity to receive first-line chemotherapy treatment safely.


Design of a single protein that spans the entire 2-V range of physiological redox potentials.
The reduction potential (E°') is a critical parameter in determining the efficiency of most biological and chemical reactions. Biology employs three classes of metalloproteins to cover the majority of the 2-V range of physiological E°'s. An ultimate test of our understanding of E°' is to find out the minimal number of proteins and their variants that can cover this entire range and the structural features responsible for the extreme E°'. We report herein the design of the protein azurin to cover a range from +970 mV to -954 mV vs. standard hydrogen electrode (SHE) by mutating only five residues and using two metal ions. Spectroscopic methods have revealed geometric parameters important for the high E°'. The knowledge gained and the resulting water-soluble redox agents with predictable E°'s, in the same scaffold with the same surface properties, will find wide applications in chemical, biochemical, biophysical, and biotechnological fields.


Ion Mobility-Mass Spectrometry Reveals Evidence of Specific Complex Formation between Human Histone Deacetylase 8 and Poly-r(C)-binding Protein 1.
Histone deacetylase 8, part of a broad class of proteins responsible for regulating transcription and many other cellular processes and directly linked to a host of human disease through its mis-function, has been canonically described as a zinc-based mettalo-enzyme for many years. Recent evidence, however, has linked this protein to iron incorporation, loaded through transient interactions with the poly r(C)-binding protein 1, a metallo-chaperone and storage protein. In this report, we construct and deploy an electrospray-mass spectrometry based assay aimed at quantifying the interaction strength between these two weakly-associated proteins, as well as the zinc and iron associated form of the histone deacetylase. Despite challenges derived from artifact protein complexes derived from the electrospray process, we use carefully-constructed positive and negative control experiments, along with detailed measurements of protein ionization efficiency to validate our dissociation constant measurements for protein dimers in this size range. Furthermore, our data strongly support that complexes between histone deacetylase 8 and poly r(C)-binding protein 1 are specific, and that they are equally strong when both zinc and iron-loaded proteins are involved, or perhaps mildly promoted in the latter case, suggesting an in vivo role for the non-canonical, iron-incorporated histone deacetylase.


Intranasal in situ gelling liquid crystal for delivery of resveratrol ameliorates memory and neuroinflammation in Alzheimer's disease.
Alzheimer's disease (AD) is an illness that affects people aged 65 or older and affects around 6.5 million in the United States. Resveratrol is a chemical obtained from natural products and it exhibits biological activity based on inhibiting the formation, depolymerization of the amyloid, and decreasing neuroinflammation. Due to the insolubility of this compound; its incorporation in surfactant-based systems was proposed to design an intranasal formulation. A range of systems has been produced by mixing oleic acid, CETETH-20 and water. Polarised light microscopy (PLM), small angle x-ray scattering (SAXS) and transmission electron microscopy (TEM) confirm the initial liquid formulation (F) presented as microemulsion (ME). After dilution, the gelled systems were characterized as hexagonal mesophase and they showed feasibility proprieties. Pharmacological assays performed after intranasal administration showed the ability to improve learning and memory in animals, as well as remission of neuroinflammation via inhibition of interleukin.


Accuracy of the sonographic fat pad sign for primary screening of pediatric elbow fractures: a preliminary study.
The purpose of this study was to evaluate the diagnostic accuracy of the sonographic fat pad sign (FPS) as a predictor for pediatric elbow fractures. This is a prospective study of children under 14 years with suspected elbow fractures. All participants underwent at first ultrasonography focused on a FPS followed by standard elbow radiographs. US findings were compared to final fracture diagnosis. 38 out of 79 children had an elbow fracture. A sonographic FPS predicted an elbow fracture with a sensitivity/specificity of 97.3/90.5 %, positive/negative likelihood ratios (LR) were 10.2/0.03 and correct/false classification rates were 93.7/6.3 %. Primary US findings were later reviewed by a blinded physician giving a congruity of 96.2 %. These secondary US findings predicted an elbow fracture with a sensitivity/specificity of 92.1/92.7 %, positive/negative LRs were 12.6/0.09 and correct/false classification rates were 92.4/7.5 %. The sonographic FPS could serve as a useful screening tool in primary evaluation of pediatric elbow injuries. If a fracture is unlikely after clinical and US evaluation, additional radiographs are dispensable, thereby potentially minimizing the radiation burden in childhood and reducing the length of stay in the Emergency Department.


Carbonic anhydrase as a tool to mitigate global warming.
The global average temperature breaks the record every year, and this unprecedented speed at which it is unfolding is causing serious climate change which in turn impacts the lives of humans and other living organisms. Thus, it is imperative to take immediate action to limit global warming. Increased CO2 emission from the industrial sector that relies on fossil fuels is the major culprit. Mitigating global warming is an uphill battle that involves an integration of technologies such as switching to renewable energy, increasing the carbon sink capacity, and implementing carbon capture and sequestration (CCS) on major sources of CO2 emissions. Among all these methods, CCS is globally accepted as a potential technology to address this climate change. CCS using carbonic anhydrase (CA) is gaining momentum due to its advantages over other conventional CCS technologies. CA is a metalloenzyme that catalyses a fundamental reaction for life, i.e. the interconversion of bicarbonate and protons from carbon dioxide and water. The practical application of CA requires stable CAs operating under harsh operational conditions. CAs from extremophilic microbes are the potential candidates for the sequestration of CO2 and conversion into useful by-products. The soluble free form of CA is expensive, unstable, and non-reusable in an industrial setup. Immobilization of CA on various support materials can provide a better alternative for application in the sequestration of CO2. The present review provides insight into several types of CAs, their distinctive characteristics, sources, and recent developments in CA immobilization strategies for application in CO2 sequestration.


Water adsorption isotherms and hydration forces for lysolipids and diacyl phospholipids.
The repulsive forces in a wide range of diacyl and monoacyl phospholipid systems have been obtained from the adsorption isotherms for water. From the exponential dependence of the repulsive pressure on the water content, information has been deduced regarding the hydration force. For diacyl phosphatidylcholines the strength of the hydration force and its characteristic decay length are in good agreement with values previously obtained by x-ray diffraction methods. For natural and synthetic diacyl phosphatidylcholines in the fluid lamellar phase, the hydration force extrapolated to zero layer separation (Po) is in the range 4-5.10(8) N.m-2 and the decay length is approximately 0.3 nm. The results for dimyristoyl, dipalmitoyl, and distearoyl phosphatidylcholines in the gel phase are very similar with Po approximately 2.5.10(8) N.m-2 and decay length of approximately 0.2 nm. Egg monomethyl phosphatidylethanolamine is less strongly hydrated: Po = 2.3.10(9) N.m-2, with a decay length of 0.3 nm. Egg phosphatidylethanolamine and bovine phosphatidylserine hydrate even more weakly with Po approximately 1.3.10(8) N.m-2 and decay length of approximately 0.15 nm. Mixtures with cholesterol or phosphatidylcholine increase both Po and the decay length for phosphatidylethanolamine to values closer to those for phosphatidylcholine. The repulsive forces deduced for egg lysophosphatidylcholine at 40 degrees C display a biphasic water dependence, with the low water phase being similar to lamellar egg phosphatidylcholine, and the phase at higher water content having a smaller value of Po = 2.10(8) N.m-2 but a longer decay length of approximately 0.45 nm, corresponding to a nonlamellar configuration. Bovine lysophosphatidylserine similarly yields values of PO = 1.2.108 N.m-2 and an effective decay length of 0.64 nm. The hydration behavior of the various diacyl phospholipids has been interpreted in terms of the mean-field molecular force theory of lipid hydration, and values deduced for the surface hydration potential of the various lipids. This analysis extends previous results on hydration forces, particularly to lysolipids and nonlamellar phases.


Plasma pharmacokinetics of lactone and carboxylate forms of 20(S)-camptothecin in anesthetized rats.
20(S)-Camptothecin exists in equilibrium between its lactone (CPT) and its carboxylate forms (Na-CPT) under stimulated physiological conditions, with the equilibrium favoring the carboxylate form. The rates of lactone hydrolysis were studied in plasma, serum albumin, and blood and were found to be faster than in aqueous buffers at equivalent pH values. From mechanistic information and in vivo activity data, the lactone appears to be the active form of the drug. It has been argued, therefore, that if an equilibrium existed between the lactone and the carboxylate, Na-CPT could be used to deliver the lactone effectively. In the present study, plasma pharmacokinetics were performed in sodium pentobarbital-anesthetized rats treated with both CPT (lactone) and the sodium salt of camptothecin (carboxylate, Na-CPT) and the lactone and carboxylate, as well as the total drug, concentration versus time profiles were assessed. It was found that plasma concentrations and AUC values for the lactone were significantly higher after dosing with CPT than after dosing with Na-CPT. After i.v. administration, the ratio of plasma lactone to carboxylate was skewed by the apparent rapid and extensive uptake of the lactone into tissues and the rapid clearance of both species. From our results, it appears that the lower in vivo activity of Na-CPT compared to that from CPT administration might be attributed to the altered conversion of carboxylate into lactone in vivo compared to that predicted from in vitro data.


Label-free detection of ovarian cancer biomarkers using whispering gallery mode imaging.
Small optical microresonators that support whispering gallery mode (WGM) resonances are emerging as powerful new platforms for biosensing. These resonators respond to changes in refractive index and potentially offer many advantages for label-free sensing. Recently we reported an approach for detecting WGM resonances based on fluorescence imaging and demonstrated its utility by quantifying the ovarian cancer marker CA-125 in buffer. Here we extend those measurements by reporting a simplified approach for launching WGM resonances using excitation light coupled into a Dove prism. The enhanced phase matching enables significant improvements in signal-to-noise, revealing the mode structure present in each resonator. As with all label-free biosensing techniques, non-specific interactions can be limiting. Here we show that standard blocking protocols reduce non-specific interactions sufficiently to enable CA-125 quantification in serum samples. Finally, fluorescence imaging of WGM resonances offers the potential for large scale multiplexed detection which is demonstrated here by simultaneously exciting and imaging over 120 microsphere resonators. For multiplexed applications, analyte identity can be encoded in the resonator size and/or location. By encoding analyte identity into microresonator size, we simultaneously quantify the putative ovarian cancer markers osteopontin (38 μm diameter sphere), CA-125 (53 μm diameter sphere), and prolactin (63 μm diameter sphere) in a single PBS assay. Together, these results show that fluorescence imaging of WGM resonances offers a promising new approach for the highly multiplexed detection of biomarkers in complex biological fluids.


The C. elegans eyes absent ortholog EYA-1 is required for tissue differentiation and plays partially redundant roles with PAX-6.
eyes absent/Eya is a conserved transcriptional coactivator involved in development of various tissues and organs in arthropods and vertebrates. In Drosophila eye development, eya functions as part of the transcriptional regulatory network along with eyeless/Pax6, sine oculis/Six and dachshund/Dach. Here, we present the first functional study of the C. elegans Eya homolog, EYA-1. Loss of EYA-1 function by RNAi and deletion mutations resulted in early larval lethality with incomplete penetrance, associated with defects of differentiation and morphogenesis of several tissues and organs. In late embryogenesis, morphological defect in the head region, pharyngeal malformation and excess cell deaths in the anterior region were observed. Consistently, EYA-1 was expressed in the nuclei of a subset of anterior cells including pharyngeal and body wall muscle cells, starting from the morphogenesis stage in embryogenesis. Interestingly, eya-1 and pax-6/Pax6 mutants showed a strong genetic interaction for larval viability and embryonic anterior morphogenesis. Thus, eya-1 appears to play a partially redundant role with pax-6 during C. elegans embryogenesis.


[Stroke due to spontaneous calcified cerebral embolus as presenting feature of calcified aortic stenosis].
We report a case of calcified aortic stenosis revealed by an ischemic stroke. An 81-year-old man with hyperlipidemia, hypertension and renal function impairment presented with acute onset of right-sided hemiparesis and aphasia. Head CT scan revealed a rounded calcified high-density mass within the distal segment of the left anterior cerebral artery, consistent with a calcified cerebral embolus, and an infarct in the left paracentral lobule. Transesophageal echocardiography demonstrated a sclerotic aortic valve. The patient was discharged from hospital on aspirin and atorvastatin, and the outcome was favorable. Calcified embolus remains a rare event and it has been not yet reported in the territory of anterior cerebral artery. It may be observed in aortic and mitral valve diseases, calcified plaques of the internal carotid artery and aortic arch. Renal failure promotes their development and is the cause of cardiovascular diseases. To date, aortic valve calcification is not considered as a marker of stroke risk, except when associated with severe stenosis or left ventricular hypertrophy.


A Case Report of Lumbar Abscess in a Transplant Recipient: Is It Always What It Seems?
The percentage of solid organ transplant recipients who develop extrapulmonary or disseminated tuberculosis (TB) is higher than the general population. In countries where the disease is endemic, TB should always be considered a diagnostic possibility, and extrapulmonary disease should also be considered. We present the case of a kidney transplant patient who initially presented for an abscess in the left dorsolateral region and was ultimately diagnosed with pulmonary and extrapulmonary TB. With the initiation of antibacillary treatment, a drug interaction with immunosuppressants was verified, and rifampicin was maintained at a minimum dose with other antibacillary drugs at full dose, subsequently showing an improvement in the clinical picture. The adverse effects of TB treatment present great difficulty owing to the interactions of antibacillary drugs with immunosuppressants. Most patients with conventional treatment can be cured, so prompt diagnosis and treatment are important.


Effect of transcutaneous posterior tibial nerve stimulation and repetitive transcranial magnetic stimulation on neurogenic overactive bladder symptoms in female patients with multiple sclerosis: The study protocol of a randomized controlled study.
Neurogenic bladder is frequently seen in patients with multiple sclerosis (MS). Electrical stimulation methods (neuromodulation) can be used for patients that have persistent symptoms despite pharmacological treatment. This study aims to compare the effects of two different neuromodulation techniques used in the treatment of neurogenic bladder. This is a single-center randomized controlled trial for MS patients with neurogenic bladder. Patients determined to be eligible according to the study criteria will be randomized into two treatment groups: the transcutaneous posterior tibial nerve stimulation (PTNS) and repetitive transcranial magnetic stimulation (rTMS) groups. Each group will include eight patients. The patients will be treated for a total of 10 sessions for two consecutive weeks. The pressure-flow study will be used to compare the initial and final urodynamic results as the primary outcome. All the participants will fill in a 3-day bladder diary before and after the treatments in each group. Patients will also be asked to complete specific questionnaires for incontinence and quality of life (QOL): Overactive Bladder Questionnaire-V8 score (OAB-V8), Incontinence Severity Index (ISI), Incontinence Quality of Life Scale score (I-QOL), International Incontinence Questionnaire (ICIQ-SF) score, and International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) score) as the secondary outcomes. An ethical approval number was obtained from the Non-Invasive Clinical Research Ethics Committee of Istanbul Medipol University (ethical approval number: 768). Support was received within the scope of the Istanbul Medipol University Scientific Research Project with project number 2020-2017. The result of this study will be published in a peer-reviewed journal. NCT05312138.


The phosphatidylcholine/lysophosphatidylcholine ratio in human plasma is an indicator of the severity of rheumatoid arthritis: investigations by 31P NMR and MALDI-TOF MS.
Lipid second messengers, e.g. lysophosphatidylcholines (LPC) are involved in the pathogenesis of inflammatory diseases, for instance, rheumatoid arthritis (RA). Unfortunately, the analysis of LPC in complex mixtures as present in body fluids is still challenging. Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) was applied for phospholipid (PL) analysis of organic extracts of synovial fluids from patients with RA as well as the corresponding plasma. These data were compared with results obtained by high resolution 31P NMR spectroscopy. Synovial fluids may be replaced by plasma since the analysis of both body fluids gives very similar results. Patients undergoing treatment with TNF-alpha inhibitors (ADALIMUMAB (HUMIRA)) were examined in order to investigate whether the clinically-significant attenuation of disease activity is accompanied by changes of the PL composition of plasma. It will be shown that especially the PC/LPC ratios of plasma represent a reliable measure of inflammation and increase upon therapy. Since plasma samples are readily available, our approach might be useful to draw conclusions before puncture of the affected joints is necessary and the PC/LPC ratio detected in plasma may serve as an indicator of RA in early stages.


Low incidence of cytomegalovirus disease in liver transplant recipients receiving sirolimus primary immunosuppression with 3-day corticosteroid taper.
Cytomegalovirus (CMV) disease is the most common infection following liver transplantation, occurring in approximately 20% of recipients. In liver transplant recipients, CMV is associated with a higher cost following transplantation, subsequent infections, and recurrent hepatitis C. Since we have initiated a prednisone-free immunosuppressive regimen in January 2000, we have noted an extremely low incidence of CMV disease in our cohort of liver transplant recipients. We report our findings here. All 150 patients transplanted between January 2000 and December 2002 with tacrolimus (or cyclosporin A) and sirolimus, and 3-day corticosteroid taper were retrospectively analyzed. Recipients who were CMV IgG negative with a CMV IgG-positive donor ("CMV mismatch") received conventional prophylactic therapy with intravenous and oral ganciclovir. The incidence of CMV disease (defined as positive tissue culture or positive immunohistochemical stain of affected tissue or CMV-DNA >3000 associated with clinical symptoms) was recorded for each patient. The proportion of "CMV mismatches" (donor CMV IgG positive, recipient CMV IgG negative) was 15%. The mean total number of days of ganciclovir prophylaxis (intravenous and/or oral) administered to "CMV mismatch" patients was 45.6 days. The incidence of CMV disease in patients receiving sirolimus primary immunosuppression was 2%. The mean time to diagnosis of CMV disease was 139 days. (1) The incidence of CMV disease is very low using a prednisone-free, sirolimus immunosuppressive regimen. (2) Two possible explanations for this finding include appropriate prophylaxis with ganciclovir and low levels of immunosuppression including the absence of prednisone.


Inclusion complexation behavior of dyestuff guest molecules by a bridged bis(cyclomaltoheptaose)[bis(beta-cyclodextrin)] with a pyromellitic acid diamide tether.
A novel bridged bis(beta-cyclodextrin) with a pyromellitic acid 2,5-diamide tether (2) has been synthesized by reaction of 6(I)-(2-aminoethyleneamino)-6-deoxycyclomaltoheptaose [mono 6-(2-aminoethyleneamino)-6-deoxy-beta-cyclodextrin] with 1,2,4,5-benzenetetracarboxylic dianhydride. Its inclusion complexation behavior with some representative dyestuffs, i.e., Acridine Red (AR), Rhodamine B (RhB), Neutral Red (NR), Brilliant Green (BG), was studied by using UV-absorption, fluorescence, and 2D NMR spectroscopy. Fluorescence titrations have been performed at 25 degrees C in pH 7.2 buffer solution to calculate the binding constants of resulting complexes. These results obtained indicated that bis(beta-cyclodextrin) 2 exhibits the strongly enhanced binding ability with all dye molecules examined compared with natural cyclodextrins. The binding modes of 2 with dye molecules have been deduced by 2D NMR experiments to establish the correlations between molecular conformations and binding constants of inclusion complexation. It is found that the improved binding ability and molecular selectivity of 2 could be attributed to double-cavity cooperative inclusion interaction and the size/shape matching between the host and guest.


Immunoglobulin levels and phagocytes in the cervical mucus plug at term of pregnancy.
To characterize the potential for adaptive immune protection in cervical mucus plugs with respect to immunoglobulin isotypes and effector cells (phagocytes). Thirty-one cervical mucus plugs were collected from healthy women in labor at term. The cervical mucus plugs were allocated either to analysis of immunoglobulins by enzyme-linked immunosorbent assay (ELISA), gel chromatography and Western blotting (n = 20) or to microscopical, including immunocytochemical, analyses. The levels of immunoglobulin in the plugs were compared to the levels in 10 samples of ovulatory cervical mucus from nonpregnant women. In the cervical mucus plugs, levels of immunoglobulin G (IgG) [median 3270 microg/mL (100-14 500)] and IgA [540 (22-2820)], but not IgM [30.5 (1.0-160)], were significantly elevated compared to cervical mucus from nonpregnant women (p < 0.02 for IgG and IgA). The IgG : IgA ratio in the plugs was also elevated (p < 0.02). The proportion of secretory immunoglobulin A (SIgA) relative to total IgA in the plugs ranged from 16 to 65% (n = 5). IgA and IgG were largely intact. Microscopically, the vagina-proximal part of the cervical mucus plugs contained bacteria and was rich in cells, mainly phagocytes. Conversely, the uterine part contained few cells. The high immunoglobulin levels in combination with the presence of phagocytes suggest a potential for adaptive immune defense in the cervical mucus plug, which, together with innate immune factors, may act as an immunological gatekeeper protecting the fetomaternal unit against infection from the vagina.


Child feeding by Nigerian mothers during acute diarrhoeal illness.
A study was conducted among mothers in a suburban community in Lagos to ascertain child feeding patterns during episodes of diarrhoea. Two hundred women with children of 6 to 36 months were selected randomly from 672 who were participating in a diarrhoea surveillance study. The vast majority restricted the consumption of yams and sugar (greater than 90%) and substantial numbers (40/50%) restricted bread and rice. On the other hand other carbohydrate foods were increased--plantain (73%) ogi-maize pap (53%) amala (56%). Of the protein foods the vast majority restricted beans (94%) and milk formula (69%) with 35% restricting meat but not fish. Few increased the intake of such foods. Beverages, fruit and vegetables were restricted by the majority; water intake was maintained. These dietary restrictions are apparently based on tradition but can have serious consequences.


Non-neutralizing epitopes induce robust hepatitis C virus (HCV)-specific antibody-dependent CD56+ natural killer cell responses in chronic HCV-infected patients.
Natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (NK-ADCC) is of considerable interest in viral infection. However, little is known about NK-ADCC responses in chronic hepatitis C virus (HCV) infection. In this study, impaired non-specific antibody-dependent CD56+ NK cell responses were observed in chronic HCV infection, as shown by decreased degranulation (extracellular CD107a expression) and interferon (IFN)-γ production in response to antibody-bound P815 cells. A peptide pool composed of epitopes recognized by anti-HCV-E1/E2 antibodies could induce pronounced HCV-specific antibody-dependent NK cell responses in sera from approximately half the chronic HCV carriers. Additionally, HCV-specific epitopes with the capacity to induce robust NK-ADCC activity were identified. Five linear NK-ADCC epitopes (aa211-aa217, aa384-aa391, aa464-aa475, aa544-aa551 and aa648-aa659 of the HCV envelope) were identified and do not overlap with putative linear neutralizing epitopes. This study revealed the dysfunctional characteristics of antibody-dependent CD56+ NK cell responses in chronic HCV carriers. The key non-neutralizing NK-ADCC epitopes identified in this study may act as new targets for immunological intervention.


Timing and sequence of primary tooth eruption in children with cleft lip and palate.
To determine the timing and sequence of eruption of primary teeth in children with complete bilateral cleft lip and palate. This cross-sectional study was conducted at the Hospital for Rehabilitation of Craniofacial Anomalies of the University of São Paulo, Bauru, SP, Brazil, with a sample of 395 children (128 girls and 267 boys) aged 0 to 48 months, with complete bilateral cleft lip and palate. Children with complete bilateral clefts presented a higher mean age of eruption of all primary teeth for both arches and both genders, compared to children without clefts. This difference was statistically significant for all teeth, except for the maxillary first molar. Mean age of eruption of most teeth was lower for girls compared to boys. The greatest delay was found for the maxillary lateral incisor, which was the eighth tooth of children with clefts of both genders. Analyzing by gender, the maxillary lateral incisor was the eighth tooth to erupt in girls and the last in boys. The results suggest an interference of the cleft on the timing and sequence of eruption of primary teeth.


Evidence for a complex interaction between the subtypes of the alpha 1-adrenoceptor.
Ligand binding studies with WB 4101 revealed that the rat aorta contains both the alpha 1a- and alpha 1b-adrenoceptor subtypes. Results obtained following treatment with the irreversible antagonists phenoxybenzamine, chlorethylclonidine or SZL-49 (4-amino-6,7-dimethoxy-2-quinazolinyl-4-(2-bicyclo[2,2,2]octa-2,5- dienylcarbonyl-2-piperazine) suggest that there is a complex interaction between the alpha 1-adrenoceptor subtypes in the aorta. Chlorethylclonidine affects only the alpha 1b-adrenoceptor, whereas the predominant action of SZL-49 is on the alpha 1a-subtype. Chlorethylclonidine significantly inhibited the response to either methoxamine or phenylephrine, agents which are selective alpha 1a-adrenoceptor agonists. Following inactivation with either chlorethylclonidine or SZL-49, the response of the rat aorta to phenylephrine was only partially antagonized by either prazosin or WB 4101. SZL-49 also inhibited the response of the rat tail artery to electrical stimulation. The response of the tail artery obtained following inactivation with SZL-49 was effectively antagonized by prazosin. Phenylephrine, prazosin or WB 4101 afforded complete protection from chlorethylclonidine adrenoceptor inactivation, while these same ligands were only partially effective against SZL-49. Either SZL-49 or chlorethylclonidine significantly impaired the irreversible adrenoceptor blocking actions of phenoxybenzamine. These results suggest: (1) only the alpha 1a-adrenoceptor subtype appears to be associated with nerve terminals in the tail artery, (2) there may be a complex interaction between the alpha 1-adrenoceptor subtypes such that both receptors must be intact and functional to observe normal agonist and antagonist interactions, (3) there may be three sites of action for agonists associated with the rat aorta.


Renal injury is accelerated by global hypoxia-inducible factor 1 alpha deficiency in a mouse model of STZ-induced diabetes.
Hypoxia inducible factor 1 (HIF-1) activates protective pathways to counteract hypoxia and prevent tissue damage in conjunction with renal injury. The aim of this study was to evaluate a role of HIF-1 in diabetes-induced kidney damage. We used a streptozotocin-induced diabetes mouse model and compared biochemical, histological and molecular parameters associated with kidney damage in Hif1α deficient (Hif1α +/- ) and wild-type mice. We showed that Hif1α deficiency accelerated pathological changes in the early stage of DN. Six weeks after diabetes-induction, Hif1α deficient mice showed more prominent changes in biochemical serum parameters associated with glomerular injury, increased expression of podocyte damage markers, and loss of podocytes compared to wild-type mice. These results indicate that Hif1α deficiency specifically affects podocyte survival in the early phase of DN, resulting in diabetic glomerular injury. In contrast, renal fibrosis was not affected by the global reduction of Hif1α, at least not in the early phase of diabetic exposure. Together our data reveal that HIF-1 has an essential role in the early response to prevent diabetes-induced tissue damage and that impaired HIF-1 signaling results in a faster progression of DN. Although the modulation of HIF-1 activity is a high-priority target for clinical treatments, further study is required to investigate HIF-1 as a potential therapeutic target for the treatment of DN.


A single one-minute, comfortable paced, stair-climbing bout reduces postprandial glucose following a mixed meal.
Postprandial blood glucose (PBG) is an independent predictor of disease and mortality risk. To date, the shortest, single, moderate-intensity exercise intervention to reduce PBG is a 1 min bout of stair stepping during an oral glucose tolerance test. Whether this effect translates to real meal consumption is unknown. Subjects (N = 30) participated in a randomized controlled crossover trial performing 0 min (seated control), 1 min, 3 min or 10 min of stair climbing and descending bouts (SCD) at a self-selected pace after consumption of a mixed meal on four separate visits. Compared to control, all SCD reduced PBG at least one timepoint: at 30-min the 3 min (-10.8 (-18.7 to -2.8) mg/dL, p = 0.010) and 10 min (-36.3 (-46.4 to -26.3) mg/dL), p < .001), and at 45-min the 1 min (-7.3 (-13.9 to -0.7) mg/dL, p = 0.030, 3 min (-8.7 (-13.9 to -3.6) mg/dL, p = 0.002 and 10 min SCD (-12.2 (-18.2 to -6.1)mg/dL, p < 0.000) reduced PBG. The area under the curve (AUC) for PBG was lower following the 3 min (-4.4% (-7.5 to -1.4%), p = 0.006) and 10 min (-8.9% (-12.4 to -5.3%), p < 0.001), while the incremental AUC (iAUC) was reduced only following the 10 min (-38.0% (-63.7 to -12.3%), p = 0.005) SCD. All SCD were rated by subjects as very light to light intensity. Single, subjectively "light" intensity stair climbing and descending bouts as short as 1 min in duration attenuate the postprandial glucose response in normal weight individuals following consumption of a mixed meal. More pronounced effects require longer bouts in a dose-dependent manner.


First-trimester maternal serum biomarkers and the risk of cerebral palsy.
To investigate whether combined first-trimester screening (cFTS) biomarkers are associated with cerebral palsy (CP) and to identify CP characteristics associated with abnormal biomarker levels. In this retrospective case-control data linkage study, we matched mothers of 435 singletons with CP from a population register to their cFTS records and selected 10 singleton pregnancy controls per case. We compared mean and abnormal levels (expressed as multiples of the median [MoMs]) of pregnancy-associated plasma protein-A (PAPP-A), beta subunit of human chorionic gonadotrophin (β-hCG), and nuchal translucency between cases and controls and between CP subgroups. Compared with control pregnancies, CP pregnancies had lower mean levels of PAPP-A (0.95 vs 1.01 MoM, p=0.02) and β-hCG (0.93 vs 0.99 MoM, p=0.02). Biomarker levels in CP pregnancies were 1.8 times more likely to be associated with abnormally low levels of PAPP-A (p<0.01), 1.4 times for β-hCG (p=0.12), and 2.6 times for low PAPP-A and β-hCG together (p=0.04). In cases with CP, an abnormally low PAPP-A level was associated with moderate preterm birth, low Apgar scores, and Gross Motor Function Classification System level V. Low β-hCG was associated with very low birthweight. Low first-trimester biomarker levels suggest a role for early pregnancy factors in some causal pathways to CP. Low first-trimester levels of biomarkers in maternal serum are associated with later cerebral palsy (CP). Early pregnancy factors have potential importance in causal pathways to CP. Causal pathways involving preterm birth, term neonatal encephalopathy, and genetic syndromes may be implicated.


Correction: Wang et al. Improve Dentin Bonding Performance Using a Hydrolytically Stable, Ether-Based Primer. J. Funct. Biomater. 2022, 13, 128.
Jirun Sun was not included as an author in the original publication [...].


Ketamine attenuates the Na+-dependent Ca2+ overload in rabbit ventricular myocytes in vitro by inhibiting late Na+ and L-type Ca2+ currents.
Intracellular Ca(2+) ([Ca(2+)]i) overload occurs in myocardial ischemia. An increase in the late sodium current (INaL) causes intracellular Na(+) overload and subsequently [Ca(2+)]i overload via the reverse-mode sodium-calcium exchanger (NCX). Thus, inhibition of INaL is a potential therapeutic target for cardiac diseases associated with [Ca(2+)]i overload. The aim of this study was to investigate the effects of ketamine on Na(+)-dependent Ca(2+) overload in ventricular myocytes in vitro. Ventricular myocytes were enzymatically isolated from hearts of rabbits. INaL, NCX current (INCX) and L-type Ca(2+) current (ICaL) were recorded using whole-cell patch-clamp technique. Myocyte shortening and [Ca(2+)]i transients were measured simultaneously using a video-based edge detection and dual excitation fluorescence photomultiplier system. Ketamine (20, 40, 80 μmol/L) inhibited INaL in a concentration-dependent manner. In the presence of sea anemone toxin II (ATX, 30 nmol/L), INaL was augmented by more than 3-fold, while ketamine concentration-dependently suppressed the ATX-augmented INaL. Ketamine (40 μmol/L) also significantly suppressed hypoxia or H2O2-induced enhancement of INaL. Furthermore, ketamine concentration-dependently attenuated ATX-induced enhancement of reverse-mode INCX. In addition, ketamine (40 μmol/L) inhibited ICaL by 33.4%. In the presence of ATX (3 nmol/L), the rate and amplitude of cell shortening and relaxation, the diastolic [Ca(2+)]i, and the rate and amplitude of [Ca(2+)]i rise and decay were significantly increased, which were reverted to control levels by tetrodotoxin (TTX, 2 μmol/L) or by ketamine (40 μmol/L). Ketamine protects isolated rabbit ventricular myocytes against [Ca(2+)]i overload by inhibiting INaL and ICaL.


CT angiography in the evaluation of intracranial occlusive disease with collateral circulation: comparison with MR angiography.
The purpose of this study is to determine whether three-dimensional computed tomography angiography (CTA) is superior to magnetic resonance angiography (MRA) in the evaluation of collateral circulation in patients with intracranial arterial occlusive disease. Conventional angiography was used as the standard reference. Collateral vessels were well visualized by CTA, but not by MRA, while conventional angiography revealed leptomeningeal collateral vessels that were filled in a retrograde fashion. CTA is superior to MRA for evaluating collateral vessels.


A case of adenocarcinoma developed in the small intestine with chronic strongyloidiasis.
We experienced a case of intestinal strongyloidiasis complicated by jejunal carcinoma. A Japanese male in his 50s, who has a 7-year medical history of duodenal ulcers, complained of loss of appetite, nausea, vomiting and diarrhea. Computed tomography and gastroduodenal endoscopic examination revealed a stenosis of the duodenum. To remove the stenosis, gastric bypass surgery was performed. The pathological diagnosis of the resected jejunum was strongyloidiasis and well-differentiated adenocarcinoma with subserosal invasion and vascular infiltration. After administration of Ivermectin, Strongyloides stercoralis was not found in any biopsies or in the specimens of the intestine, which were resected due to cancer recurrence 2 years later. There are three possibilities for the reason of coexistence of S. stercoralis and adenocarcinoma: S. stercoralis caused the adenocarcinoma, S. stercoralis moved to the carcinoma, or just coincidence. Although it is difficult to prove a causal relationship between S. stercoralis and adenocarcinoma, this is the first report of adenocarcinoma developed in the jejunum with chronic strongyloidiasis. The number of nematode infections, including strongyloidiasis, is decreasing in Japan, although not worldwide. Therefore, it should be considered in patients with prolonged intestinal ulcers.


Real-World Use of 3rd Line Therapy for Multiple Myeloma in Austria: An Austrian Myeloma Registry (AMR) Analysis of the Therapeutic Landscape and Clinical Outcomes prior to the Use of Next Generation Myeloma Therapeutics.
Clinical trials demonstrate improving survival in patients with multiple myeloma (MM) after treatment. However, it is unclear whether increased survival translates to a similar benefit in a real world setting. We analyzed the overall survival of 347 multiple myeloma patients in Austria by means of a national registry (AMR), focused on results from 3rd and later lines of therapy. This benchmark was chosen to define a baseline prior to the broad application of upcoming 2nd generation drugs (carfilzomib, pomalidomide). Projected 10 years survival for patients with MM in Austria is estimated to be 56% in patients diagnosed in between the years 2011-2014, 21% in patients with a diagnosis made between 2000-2005, and 39% in those with a diagnosis made between 2006-2010). For the same intervals a significant increase in the use of both bortezomib, lenalidomide and thalidomide-so called IMiDs (from 2005 onwards) and their simultaneous use in combination therapies (from 2010 onwards) could be shown. The use of autologous transplantation (ASCT) remained more or less constant at ~ 35% of patients in the 1st line setting over the whole period, comparing well to international practice patterns, while the use of 2nd line ASCT increased from 5.5% to 18.7% of patients. Patients in 3rd or later line treatment (n = 105), showed that even in relapsed and refractory disease median survival was 27 months with a considerable proportion of long-term survivors (~20%). With the expected emergence of additional active anti-myeloma compounds, we aim to assess survival in patients with relapsed and refractory MM.


A Retrospective, Long-term Follow-up of the Clinical Outcomes and Cost-effectiveness of Single-anesthetic Multiple Total Joint Procedures in Hemophilic Arthropathy.
Although total joint replacement (TJR) procedures are efficacious, perioperative high-dose factors replacement therapy (FRT) to avoid catastrophic bleeding represents a significant hurdle, particularly for patients with multiple joint affection. Double simultaneous bilateral TJRs were reported as safe and cost-effective. However, little is known about multiple TJRs. The feasibility and effects remain debatable. Surgeons need to weigh the high cost of FRT against safety. Accordingly, we aimed to evaluate the clinical outcomes and cost-effectiveness of single-anesthetic multiple-joint procedures of lower limbs in end-stage hemophilic arthropathy. Our retrospective cohort study retrieved data from an inpatient database of patients with hemophilia who underwent total knee arthroplasty (TKA), total hip arthroplasty (THA), and/or ankle arthrodesis from January 2000 to April 2016. Complications, hospital stays, transfusion, doses of clotting factor, medical costs, range of motion (ROM), Harris hip scores (HHSs) and Hospital for special surgery knee scores (HSSs) were recorded. A P value < 0.05 was considered significant. A total number of 81 patients were included in this study, among which 89 TKAs and 52 THAs were performed. Compared to the single TJR group, the simultaneous multiple TJR group showed a significantly higher rate of blood transfusions (P < 0.05). But no significant differences were found in the length of hospital stays, factor consumption, hospitalization costs excluding prosthesis expenses, and total complication rates. Finally, similar postoperative ROM, HHS, and HSS were witnessed in two groups (P value > 0.05). Our data indicated that simultaneous multiple TJRs are a safe and cost-effective choice for treating hemophilic patients with multiple HA-affected lower limb joints.


Bullying in the family: sibling bullying.
Sibling relationships have a substantial and lasting effect on children's development. Many siblings experience some occasional conflict, however, up to 40% are exposed to sibling bullying every week, a repeated and harmful form of intrafamilial aggression. We review evidence on the precursors, factors relating to peer bullying, and mental health consequences of sibling bullying. Parenting quality and behaviour are the intrafamilial factors most strongly associated with bullying between siblings. Sibling bullying increases the risk of being involved in peer bullying, and is independently associated with concurrent and early adult emotional problems, including distress, depression, and self-harm. The effects appear to be cumulative, with those children bullied by both siblings and peers having highly increased emotional problems compared with those bullied by siblings or peers only, probably because they have no safe place to escape from bullying. The link between sibling and peer bullying suggests interventions need to start at home. Health professionals should ask about sibling bullying and interventions are needed for families to prevent and reduce the health burden associated with sibling bullying.


Valorisation of the green waste parts from turnip, radish and wild cardoon: Nutritional value, phenolic profile and bioactivity evaluation.
The recovery of bio-wastes to obtain high added value compounds is of great interest for the pharmaceutical, medicinal and food industries. Therefore, the aerial parts of turnip (Brassica rapa L.), radish (Raphanus sativus L.) and leaf blade of wild cardoon (Cynara cardunculus L. var. sylvestris (Lamk) Fiori) were characterized regarding their nutritional composition, as also their content in soluble sugars, organic acids, fatty acids, and tocopherols. Furthermore, their hydroethanolic extracts and infusion preparations, were profiled regarding individual phenolic compounds by HPLC-DAD/ESI-MS and their antioxidant, antibacterial and hepatotoxic activities were evaluated. Regarding the nutritional content, wild cardoon revealed the best results, however it was radish and turnip that showed higher values for organic acids and phenolic compounds. The hydroethanolic extract and infusion preparation of wild cardoon stood out for its antioxidant and antibacterial activity. Overall, the hydroethanolic extracts seemed more effective (regarding antioxidant and antibacterial activity) than the infusions. Total phenolic acids proved to be strongly correlated with the antioxidant and antibacterial (against Morganella morganii) activities. This study showed that the discarded parts of these plants can be used as an important natural source of valuable nutrient content and new and safe bioactive compounds, beneficial for human health. Moreover, the extraction of those compounds from underused parts of turnip, radish and cardoon could be used to preserve foods, avoiding artificial additives and thus, contributing to the development of new natural ingredients.


Adult onset hemophagocytic lymphohistiocytosis prognosis is affected by underlying disease and coexisting viral infection: analysis of a single institution series of 35 patients.
Adult onset hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome, which can develop as a complication of many disorders. Early diagnosis is essential in order to avoid a fatal outcome. To confirm the diagnosis of acquired HLH made in a single institution series of adult patients with HLH-04 criteria, we applied the HScore and evaluated prognostic factors associated with clinical outcome. The median age of 35 patients was 54 (range 17-81), M/F ratio was 20/15. In 26/35 (74.3%) patients, an underlying haematological disease was present (2 Multicentric Castleman Disease, 10 B-cell Non-Hodgkin Lymphoma [NHL] and 14 T/NK-cell NHL); an autoimmune disorder was observed in four (11.4%) patients (one Still Disease, one undifferentiated connective tissue disease and two haemolytic anaemia); in five (14.3%), no underlying disease was identified. A concomitant infection by EBV was observed in 10 patients (28.6%), CMV in 8 (22.9%), HHV8 in 6 (17.1%) and HIV in 1 (2.9%). Hyperferritinemia, fever and splenomegaly were present in more than 90% of patients, whereas bone marrow hemophagocytosis in 51% of cases only. According to HScore, 34/35 patients had a >75% and 32/35 >93% probability of HLH. Four-year overall survival and HLH-free survival were 17.8% (CI 1.9-33.8) and 23.8% (CI 7.3-40.3), respectively. By multivariate analysis, presence of oedema and hyperbilirubinemia were predictors of death, whereas there was a statistically significant trend for viral infection as predictor of poor prognosis. B-NHL diagnosis was confirmed as associated to a better prognosis in comparison with T/NK lymphoma (4-year HFS 53.3% vs. 0%, p = 0.09) and similar to other aetiologies. Copyright © 2016 John Wiley & Sons, Ltd.


A behavioral demonstration of overconfidence in judgment.
Overprecision-an excessive confidence that one knows the truth-is both the most durable and the least understood form of overconfidence. This article outlines an approach to the study of overprecision that avoids some of the methodological problems of other approaches and better reflects the way uncertainty affects choices in everyday life. We measured the precision in judgment implied by people's tendency to adjust their point estimates of an uncertain quantity in response to the costs of overestimating or underestimating the correct answer. The results revealed robust overprecision. People adjusted their estimates less than they should have given their actual knowledge, and this effect was driven by their subjective confidence.


Fast writer adaptation with style extractor network for handwritten text recognition.
Writing style is an abstract attribute in handwritten text. It plays an important role in recognition systems and is not easy to define explicitly. Considering the effect of writing style, a writer adaptation method is proposed to transform a writer-independent recognizer toward a particular writer. This transformation has the potential to significantly increase accuracy. In this paper, under the deep learning framework, we propose a general fast writer adaptation solution. Specifically, without depending on other complex skills, a well designed style extractor network (SEN) trained by identification loss (IDL) is introduced to explicitly extract personalized writer information. The architecture of SEN consists of a stack of convolutional layers followed by a recurrent neural network with gated recurrent units to remove semantic context and retain writer information. Then, the outputs of the GRU are further integrated into a one-dimensional vector that is adopted to represent writing style. Finally, the extracted style information is fed into the writer-independent recognizer to achieve adaptation. Validated on offline handwritten text recognition tasks, the proposed fast sentence-level adaptation achieves remarkable improvements in Chinese and English text recognition tasks. Specifically, in the HETR task, a multi-information fusion network that is equipped with a hybrid attention mechanism and that integrates visual features, context features and writing style is proposed. In addition, under the same condition (only one writer-specific text line used as adaptation data), the proposed solution, without consuming extra time, can significantly outperform the previous multiple-pass decoding method. The code is available at https://github.com/Wukong90/Handwritten-Text-Recognition.


Environmental tobacco smoke of youngsters in Czech Republic, Hungary, Poland and Slovakia--findings from the Global Youth Tobacco Survey (GYTS).
To present data on Environmental Tobacco Smoke (ETS), Global Youth Tobacco Survey (GYTS), Czech Republic, Hungary, Poland and Slovakia. A questionnaire survey of a representative sample of 16 918 schoolchildren aged 13-15 years (2002-2003). Exposure to ETS was reported more frequently in public places than in homes and more frequently from current smokers (CS) than from never smokers (NS). ETS in homes was lower in Czech (57.6% in CS, 24.7% in NS) than in other countries (the highest in Poland: 93.0% in CS, 80.9% in NS). ETS in public places was highest in Hungary (96.9% in CS, 89.2% in NS), lowest in Czech (90.1% in CS, 57.3% in NS). Most students considered ETS as harmful and presented positive attitudes towards smoking ban. ETS in studied countries, save the Czech Republic, exceeded the global prevalence, while the situation is better than in numerous other Eastern European countries.


Inorganometallics (Transition Metal-Metalloid Complexes) and Catalysis.
While the formation and breaking of transition metal (TM)-carbon bonds plays a pivotal role in the catalysis of organic compounds, the reactivity of inorganometallic species, that is, those involving the transition metal (TM)-metalloid (E) bond, is of key importance in most conversions of metalloid derivatives catalyzed by TM complexes. This Review presents the background of inorganometallic catalysis and its development over the last 15 years. The results of mechanistic studies presented in the Review are related to the occurrence of TM-E and TM-H compounds as reactive intermediates in the catalytic transformations of selected metalloids (E = B, Si, Ge, Sn, As, Sb, or Te). The Review illustrates the significance of inorganometallics in catalysis of the following processes: addition of metalloid-hydrogen and metalloid-metalloid bonds to unsaturated compounds; activation and functionalization of C-H bonds and C-X bonds with hydrometalloids and bismetalloids; activation and functionalization of C-H bonds with vinylmetalloids, metalloid halides, and sulfonates; and dehydrocoupling of hydrometalloids. This first Review on inorganometallic catalysis sums up the developments in the catalytic methods for the synthesis of organometalloid compounds and their applications in advanced organic synthesis as a part of tandem reactions.


Age-induced changes in single locus coeruleus brain transplants grown in oculo: an in vivo electrochemical study.
Brain stem tissue from fetal Sprague-Dawley rats containing the nucleus locus coeruleus (LC) was transplanted into the anterior chamber of the eye of young adult host rats and was studied at 4-6 months (young control) or 24-28 months after grafting (old). High-speed in vivo electrochemical measurements were used to characterize the potassium-evoked synaptic overflow of norepinephrine (NE) in both young and aged LC brain grafts. The amplitudes of potassium-evoked NE overflow were attenuated in the aged grafts as compared to the young LC grafts. In addition, the rise times of potassium-evoked responses were longer in the old LC grafts than in the young transplants. In contrast, the NE content of aged LC grafts, as determined by high-performance liquid chromatography coupled with electrochemical detection (HPLC-EC), was only slightly diminished and not significantly different from the NE levels seen in young LC grafts. However, light microscopical evaluation using tyrosine-hydroxylase immunocytochemistry revealed pyknotic cell bodies and fluorescent accumulations in aged locus coeruleus transplants which were indicative of degeneration in these grafts. The present data demonstrate a significant age-related decline in the presynaptic function of NE-containing neurons in intraocular locus coeruleus transplants of Sprague-Dawley rats.


Involvement of epimutations in meningioma.
Epimutations are heritable and reversible cell markers, which can influence cell function going beyond the effects of DNA mutations. They result from multiple and coordinated mechanisms able to modulate gene expression. Regarding the significance of epigenetics in meningioma, few and somehow contradictory results are available, although promising information has been obtained. Here we highlight the most recent advances about the impact of DNA methylation, histone modifications, and microRNA regulation on meningioma development as well as the interplay between genetic and epigenetic alterations. Data indicate that epigenetics can help to identify novel candidate genes for the management and treatment of meningioma.


Isolation of bacteriophages against multidrug resistant Acinetobacter baumannii.
Increasing multiple drug resistant (MDR) strains of Acinetobacter baumannii has aggravated curiosity in development of alternative therapy. Bacteriophages are often considered as alternative agents for controlling A. baumannii infections. In the present study two lytic phages for MDR A. baumannii were isolated and their efficacy and host ranges were evaluated. The phages were isolated from hospital wastewater. Electron microscopy revealed that IsfAB78 might belong to Myoviridae and IsfAB39 to Podoviridae. Initial characterization of phages showed that they have narrow host range and failed to infect relative and non-relative bacteria. Both phages decreased the A. baumannii turbidity significantly, indicating that these isolated phages may be considered as candidates for phage therapy.


[A new method for the demonstration of the Bordetella bronchiseptica capsule in electron microscopy].
A new and rapid working method is presented for electronmicroscopic preparation of capsules from gram negative bacteria, e.g. Bordetella bronchiseptica and Pasteurella multocida. The advantage of the new technique is the availability of the results within 30 min after starting the preparation. The staining of the capsule by alcian blue has to be done as a first step together with glutaraldehyde fixation, before staining the bacterial cell with phosphotungstic acid. The new staining technic also reveals structural details of the capsule. The described procedure was found to be useful in controlling the development of the bacterial capsule depending on culture media for propagation and maintenance of the above mentioned bacteria.


Human immunodeficiency virus positive status disclosure among children in northwest Ethiopia: a cross-sectional study.
Human Immunodeficiency Virus positive status disclosure is an essential component of pediatric care and longterm disease management. However, one of the greatest challenges that caregiver/mothers and health care workers face is the disclosure of HIV positive status to children living with the virus. Therefore, the objective of this study was to assess HIV positive status disclosure and associated factors among HIV positive children in northwest Ethiopia. Institutional based cross-sectional study was conducted among 417 sampled HIV positive children attending pediatric ART clinics of public health facilities from February 01 to March 30 2020 in northwest Ethiopia. Simple random sampling technique was used to select study participants. A structured interviewer administered questionnaire was used for data collection and the collected data entered into Epi data software. Binary logistic regression analysis was done and variables with P-value <0.05 was considered as a significant predictors of HIV positive status disclosure of HIV positive children. From 417 sampled population, 390 were involved in this study making 93.5% response rate. The study revealed that 53.6% with 95% CI (0.486-0.586) of HIV positive children knew their HIV positive sero status. Caregiver/mothers who had greater than three family sizes (AOR=1.984, 95% CI=1.046-3.762), children whose ages greater than 10 years (AOR=6.679, 95% CI=3.372-13.227) and children on ART for more than 5 years (AOR=8.96, 95% CI=6.402-12.257) were predictors of HIV positive status disclosure. The HIV positive status disclosure was high in the study area relative to other studies. Family size, children age, and length of children on ART were predictors of HIV positive status disclosure for HIV positive children. Health care providers, especially those working at pediatrics ART clinics should keep these factors in mid while working with caregivers to encourage disclosure of HIV positive status.


Posterior capsule opacification. Part 1: Experimental investigations.
Posterior capsule opacification (PCO) is the most frequent complication associated with decreased vision after cataract surgery. Previous methods of preventing PCO have not proven to be practical, effective, and safe for routine clinical procedure, but some novel concepts and methods have recently been developed. This 2-part review looks at clinical and experimental investigations of PCO, focusing on developments since 1992. Clinical aspects will be presented in a later issue. This paper addresses (1) in vitro models for PCO research; (2) pathophysiology and molecular biology of lens epithelial cells (LECs); (3) prevention of PCO. Of special interest are methods of culturing human LECs obtained by capsulotomy during cataract surgery, including those obtained with an intact capsular bag, to provide an in vitro model for investigating the pathophysiology of LECs; the effect of a sharp bend in the lens capsule that induces contact inhibition of migrating LECs; more specific inhibition of migrating LECs using an immunotoxin, b-FGF-saporin, or EDTA and RGD-peptides.


Complex association of self-rated health, depression, functional ability with loneliness in rural community-dwelling older people.
This study aimed to explore whether and how self-rated health, depression and functional ability interactively associated with loneliness using a sample group of older adults residing in China rural communities. Data on socio-demographic information, self-rated health, depressive symptoms, functional ability and loneliness (quantified via a single question) were collected from 1009 participants. Cross-tabulations with chi-square test, bivariate correlations, and Classification and Regression Tree (CART) models were employed for analysis. We found that 45.1% of the participants were classified as lonely. Our results gain insight into the hierarchical order of predictors for the presence of loneliness, suggesting that there was a significant interaction between functional ability and depressive symptoms while self-rated health was not a significant factor. The probability of loneliness increased with the combination of limited functional ability and depression, and varied with different interaction of functional ability, depressive symptoms, and marital status, respectively. Notably, while there were some differences, similar associations were observed among older male and female respondents. To delay or reduce loneliness, early detection which focuses on older people who report limitations in functional ability, depression, and being female, offers opportunities to start early interventions. Our findings might be helpful not only in designing and implementing loneliness prevention programs but also in improving healthcare for older rural community-dwelling people.


Everyday life and social consequences of cerebral palsy.
The disclosure of diagnosis for a child with cerebral palsy (CP) is a highly stressful experience to the parents. The experience can be alleviated by clarity, empathy, and an emphasis on the child's resources and abilities. Despite chronic stress many families function well and manage to strengthen the child and family's resources through spousal and family support, maintenance of hope for further development, and active care taking. The caregiver burden can be divided into an objective burden (socio-structural constraints) and a subjective burden (emotional distress). The subjective burden of care seems less important, as illustrated by the quote: "We are tired, not sad." Quality of life is similar in 8- to 12-year-old European children with CP and controls, whereas participation in daily life was lower for children with CP. Participation varies significantly among countries implying that some countries can improve in this area. In a study from Denmark only 29% of adults with CP were employed (versus 88% of controls), 25% were cohabitating, and 20% had children. These long-term achievements could be predicted from development quotient, CP type, and motor impairment at age 5. The goal of habilitation is integration into society, which is not achieved for the majority.


Theories of urinary incontinence causation: aetiological descriptions by sub-Saharan African women.
To describe the perceived causes of urinary incontinence (UI) and factors associated with awareness of causes of UI among women in the community. Secondary analysis of data extracted from the Ibadan Urinary Incontinence Household Survey (IUIHS), a multi-stage community survey conducted among 5001 women in Nigeria. The mean age was 34.8 years (SD=14.2). The majority had at least secondary education and were currently married. Within this population, 13% had ever leaked urine. On their perception of possible aetiological factors of UI, 20.5% mentioned pelvic floor or bladder-related causes such as stress incontinence triggers and bladder problems; 14.6% mentioned uncontrollable factors such as medical comorbidity, age and prior surgery; 8.8% attributed the cause to being female; and 6.8% mentioned sex-related factors. Multiple logistic regression analysis revealed significantly lower odds of awareness of the aetiology of urinary incontinence among women aged less than 30 years, those with lower level of education, rural women, those with five or more children and women without history of urine leakage. The study shows a low level of awareness of possible cause of UI amongst women surveyed. We recommend health education and mobilization of women on the right aetiological factors of UI.


What are self-generated actions?
The concept of self-generated action is controversial, despite extensive study of its neural basis. Why is this concept so troublesome? We analyse the concept of self-generated action as employed by Passingham, Bengtsson, and Lau (2010a, 2010b). There are two definitions of self-generated action; as operant action and as underdetermined action. The latter draws on subjective experience. Experiments on action awareness suggest that experience may not be a good guide for defining self-generated action. Nevertheless, we agree with Passingham and colleagues that self-generated actions exist distinct from operant actions. But defining 'self-generated' by the degree of involvement of an endogenous process risks regress. We sketch an alternative account of self-generated action that tries to avoid these problems to make self-generated actions accessible to experimental science.


Right ventricular outflow tract reconstruction in patients with persistent truncus arteriosus: a 15-year experience in a single Japanese center.
The present study analyzes a 15-year experience of repairing persistent truncus arteriosus (PTA) with a consistent policy of right ventricular outflow tract (RVOT) reconstruction (ie, direct anastomosis). This retrospective study included 13 consecutive patients with PTA (8 type I PTA, 5 type II) who underwent primary repair from September 1992 to December 2006. Median age and body weight at surgery were 21 days and 2.9 kg, respectively. All but 1 patient underwent RVOT reconstruction by direct anastomosis with a monocusp patch. There were 2 operative deaths (12%). No patient had a pulmonary hypertensive crisis. The median duration of ventilation was 5 days. Another patient died from cardiogenic shock resulting from late cardiac tamponade 2 months after surgery. Four patients (40%) required balloon angioplasty and 5 (50%) required re-operation for branch pulmonary artery and/or conduit obstruction during the median follow-up period of 70 months (44-174 months). Freedom from all re-interventions and re-operation at 5 years was 50% (95% confidence limits, 19-81%) and 60% (95% confidence limits, 30-91%), respectively. Reasonable early and long-term results can be achieved with direct anastomosis. Further reduction of the re-intervention rate could be attained by refining the surgical techniques and catheter intervention strategies.


Effect of a dietary-induced weight loss on liver enzymes in obese subjects.
Weight loss was shown to be associated with improvements in liver enzymes and improvements of nonalcoholic fatty liver disease. However, some evidence also shows that liver enzymes may transiently increase immediately after a dietary-induced weight loss. The aim was to assess the outcome of liver enzymes after a low-calorie diet (LCD) as well as during a follow-up period and to identify predictors for potential changes in these liver enzymes. In this post hoc analysis of an existing database, liver enzymes were assessed before and immediately after a highly standardized soy-based meal replacement LCD providing 800 kcal/d, as well as 32 and 60 wk after the end of the LCD. Data emanating from 147 obese subjects (104 women and 43 men) without known hepatic disease were included in this study. The LCD led to a median weight loss of 12.1 kg (range: 7.7-27.6 kg). In men, a significant decrease in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) was observed immediately after the LCD, whereas, in women, these enzymes increased significantly, although mildly; however, this increase was transient. Sex was the only identifiable predictor of these changes in liver enzymes. This study showed that mild, transient increases in ALT and AST values can be observed immediately after an LCD in women, but not in men. These changes are probably of multifactorial origin and may be considered as benign as long as they remain transient.


Temporal information processing by alcoholics.
In time-discrimination tests using visual and auditory stimuli, more information was transmitted by social drinkers than by alcoholics, and cognitively unimpaired alcoholics transmitted more information than did cognitively impaired alcoholics.


The mechanism of root growth inhibition by the endocrine disruptor bisphenol A (BPA).
Bisphenol A (BPA) is a harmful environmental contaminant acting as an endocrine disruptor in animals, but it also affects growth and development in plants. Here, we have elucidated the functional mechanism of root growth inhibition by BPA in Arabidopsis thaliana using mutants, reporter lines and a pharmacological approach. In response to 10 ppm BPA, fresh weight and main root length were reduced, while auxin levels increased. BPA inhibited root growth by reducing root cell length in the elongation zone by suppressing expansin expression and by decreasing the length of the meristem zone by repressing cell division. The inhibition of cell elongation and cell division was attributed to the enhanced accumulation/redistribution of auxin in the elongation zone and meristem zone in response to BPA. Correspondingly, the expressions of most auxin biosynthesis and transporter genes were enhanced in roots by BPA. Taken together, it is assumed that the endocrine disruptor BPA inhibits primary root growth by inhibiting cell elongation and division through auxin accumulation/redistribution in Arabidopsis. This study will contribute to understanding how BPA affects growth and development in plants.


Molecular Subtypes of Urothelial Bladder Cancer: Results from a Meta-cohort Analysis of 2411 Tumors.
Previous molecular subtyping for bladder carcinoma (BLCA) involved <450 samples, with diverse classifications. To identify molecular subtypes by curating a large BLCA dataset. Gene expression publicly available were combined and reanalyzed. The dataset contained 2411 unique tumors encompassing non-muscle-invasive (NMIBC) and muscle-invasive BLCA (MIBC). Subtypes were reproduced on The Cancer Genome Atlas, UROMOL, and IMvigor210. Subtypes were assigned by gene expression. Kaplan-Meier analyses were performed for subtype-clinical outcome correlations; Chi-square/Fisher exact tests were used for subtype-clinicopathological parameters associations. We identified six molecular subtypes with different overall survival (OS) and molecular features. Subtype Neural-like (median OS, 87 mo) is prevalent in MIBC and characterized by high WNT/β-catenin signaling. HER2-like (107.7 mo) is distributed evenly across NMIBC and MIBC, with higher ERBB2 amplification and signaling. Papillary-like (>135 mo), an NMIBC subtype enriched in urothelial differentiation genes, shows a high frequency of actionable FGFR3 mutations, amplifications, and FGFR3-TACC3 fusion. Luminal-like (91.7 mo), predominantly NMIBC, has higher MAPK signaling and more KRAS and KMT2C/D mutations than other subtypes. Mesenchymal-like (MES; 86.6 mo) and Squamous-cell carcinoma-like (SCC; 20.6 mo) are predominant in MIBC. MES is high in AXL signaling, whereas SCC has elevated PD1, CTLA4 signaling, and macrophage M2 infiltration. About 20% of NMIBCs show MIBC subtype traits and a lower 5-yr OS rate than Papillary-like NMIBC (81% vs 96%). The main limitations of our study are the incomplete clinical annotation, and the analyses were based on transcriptome subset due to comparisons across gene expression quantification technologies. BLCA can be stratified into six molecular subtypes. NMIBC, with a high risk of progression, displays the molecular features of MIBC. Biomarkers are urgently needed to guide patient treatment selection and avoid unnecessary toxicities in those who fail to respond. We believe molecular subtyping is a promising way to tailor disease management for those who will benefit most.


Controllable synthesis of flake-like Al-doped ZnO nanostructures and its application in inverted organic solar cells.
Flake-like Al-doped ZnO (AZO) nanostructures including dense AZO nanorods were obtained via a low-temperature (100°C) hydrothermal process. By doping and varying Al concentrations, the electrical conductivity (σ) and morphology of the AZO nanostructures can be readily controlled. The effect of σ and morphology of the AZO nanostructures on the performance of the inverted organic solar cells (IOSCs) was studied. It presents that the optimized power conversion efficiency of the AZO-based IOSCs is improved by approximately 58.7% compared with that of un-doped ZnO-based IOSCs. This is attributed to that the flake-like AZO nanostructures of high σ and tunable morphology not only provide a high-conduction pathway to facilitate electron transport but also lead to a large interfacial area for exciton dissociation and charge collection by electrodes.


Racial/Ethnic Disparities in Pain Treatment: Evidence From Oregon Emergency Medical Services Agencies.
Despite the critical role that Emergency Medical Services (EMS) provides in the health care system, racial/ethnic treatment disparities in EMS remain relatively unexamined. To investigate racial/ethnic treatment disparities in pain assessment and pain medication administration in EMS. A retrospective analysis was performed on 25,732 EMS encounters from 2015 to 2017 recorded in the Oregon Emergency Medical Services Information System using multivariate logistic regression models to examine the role of patient race/ethnicity in pain assessment and pain medication administration among patients with a traumatic injury. Hispanic and Asian patients were less likely to receive a pain assessment procedure and all racial/ethnic patients were less likely to receive pain medications compared with white patients. In particular, regarding the adjusted likelihood of receiving a pain assessment procedure, Hispanic patients were 21% less likely [95% confidence interval (CI), 10%-30%; P<0.001], Asian patients were 31% less likely (95% CI, 16%-43%; P<0.001) when compared with white patients. Regarding the adjusted likelihood of receiving any pain medications, black patients were 32% less likely (95% CI, 21%-42%; P<0.001), Hispanic patients were 21% less likely (95% CI, 7%-32%; P<0.01), and Asian patients were 24% less likely (95% CI, 1%-41%; P<0.05) when compared with white patients. Racial/ethnic minorities were more likely to experience disadvantages in EMS treatment in Oregon. Hispanic and Asian patients who requested EMS services in Oregon for traumatic injuries were less likely to have their pain assessed and all racial/ethnicity patients were less likely to be treated with pain medications when compared with white patients.


Decrease of CD4+ T-lymphocytes in children exposed to environmental lead.
The effects of environmental lead on the immune system of young children were assessed by determining the peripheral blood lymphocytes CD3+, CD4+, CD8+, B(CD19+) counts, and natural killer (CD16+CD56+) cells in 35 preschool children whose mean blood lead level was 140.6 microg/L. The results were compared to an age- and sex-matched control group with a mean blood lead level of 64.3 microg/L. Compared to the controls, a significant reduction in the percentage of CD4+ cells and a significant increase of CD8+ cells were seen in the high-lead group. The negative correlation between the percentage of CD4+ cells and blood lead levels was found to be significant (p<0.01). These results suggest that exposure to environmental lead might result in alterations in the immune function of young children.


[Mouse melanoma cell line B16F10-derived conditioned medium inhibits sodium L-ascorbate-induced B16F10 cell apoptosis].
To investigate the effect of mouse melanoma cell line B16F10-derived conditioned medium on the apoptosis of B16F10 cells. B16F10 cells were cultured in high-glucose DMEM in the presence of 10% fetal bovine serum, and upon cell confluence, the growth medium was replaced with serum-free high-glucose DMEM. After 8 h, the medium was collected and infiltrated to serve as the conditioned medium. B16F10 cells cultured in normal growth medium or the conditioned medium were exposed to 10 mmol/L sodium L-ascorbate, and the cell apoptosis was analyzed. The ingredients in the conditioned medium with relative molecular mass less or more than 5 000 were extracted to assess their effect on sodium L-ascorbate-induced cell apoptosis. The conditioned medium for B16F10 cells significantly inhibited cell apoptosis induced by sodium L-ascorbate, and the effective ingredients in the medium showed a relative molecular mass below 5,000. Mouse melanoma cell line B16F10-derived conditioned medium can suppress sodium L-ascorbate- induced apoptosis of B16F10 cells, and the ingredients with relative molecular mass less than 5 000 are responsible for this effect.


Effect of Microcystis aeruginosa and Nodularia spumigena on survival of Eurytemora affinis and the embryonic and larval development of the Baltic herring Clupea harengus membras.
Laboratory experiments were carried out to investigate the effect of two strains of Microcystis aeruginosa and a strain of Nodularia spumigena on the survival of Eurytemora affinis (Copepoda) and on the embryonic and larval development of the Baltic spring-spawning herring Clupea harengus membras. The trials were made in water taken from Pärnu Bay, at a salinity of 3.7-5.1 psu, a constant temperature (15 degrees C +/- 1 degrees C in trials with Eurytemora and herring embryos; 18 degrees C +/- 2 degrees C with herring larvae), and an oxygen concentration of 8.8-10.4 ppm. The strains tested had a negative impact on the survival of Eurytemora, as well as on the embryonic development and hatching regime of the Baltic herring. In Eurytemora the response depended on the sex of the animals: the survival was clearly higher in females. In the embryonic stages of herring, the influence resulted in an increase in deviations from the normal pattern of development and a higher mortality. The impact of the strains on the larval development of herring was rather moderate.


Detection of cancer cells in peripheral blood of stomach cancer patients using RT-PCR amplification of tumour-specific mRNAs.
RT-PCR amplification of tumour-specific mRNA has been used for the detection of cancer cells in peripheral blood. To evaluate the characteristics of the tumour specific mRNA species in peripheral blood of stomach cancer patients. We analysed CEA, GalNAc-T, MUC-1, c-MET and hTERT mRNA expression in the stomach cancer cell lines and tissues, lymph nodes and peripheral blood of stomach cancer patients using RT-PCR. In RT-PCR analysis of the peripheral blood, 4%, 8%, 21%, 46%, and 100% of stomach cancer patients were positive for CEA, GalNAc-T, c-MET, hTERT and MUC-1 mRNA, respectively, but MUC-1 mRNA was also positive in all normal blood samples. The detection of hTERT mRNA was correlated with poor differentiation (P = 0.01) and lymph node metastasis (P = 0.009). The presence of c-MET mRNA was correlated with T stage (P = 0.025), lymph node metastasis (P = 0.036), distant metastasis (P = 0.031), and stage of the stomach cancer (P = 0.023). Our study suggest that hTERT mRNA in peripheral blood can be a molecular marker for gastric cancer. We also showed that each molecular marker can be correlated with the clinicopathological features of the patients.


Genome-Informed Design of a LAMP Assay for the Specific Detection of the Strain of 'Candidatus Phytoplasma asteris' Phytoplasma Occurring in Grapevines in South Africa.
Grapevine yellows is one of the most damaging phytoplasma-associated diseases worldwide. It is linked to several phytoplasma species, which can vary regionally due to phytoplasma and insect-vector diversity. Specific, rapid, and reliable detection of the grapevine yellows pathogen has an important role in phytoplasma control. The purpose of this study was to develop and validate a specific loop-mediated isothermal amplification (LAMP) assay for detection of a distinct strain of grapevine 'Candidatus Phytoplasma asteris' that is present in South Africa, through implementation of a genome-informed test design approach. Several freely available, user-friendly, web-based tools were coupled to design the specific LAMP assays. The criteria for selection of the assays were set for each step of the process, which resulted in four experimentally operative LAMP assays that targeted the ftsH/hflB gene region, specific to the aster yellows phytoplasma strain from South Africa. A real-time PCR was developed, targeting the same genetic region, to provide extensive validation of the LAMP assay. The validated molecular assays are highly specific to the targeted aster yellows phytoplasma strain from South Africa, with good sensitivity and reproducibility. We show a genome-informed molecular test design and an efficient validation approach for molecular tests if reference and sample materials are sparse and hard to obtain.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Rapid 3D absolute B1 + mapping using a sandwiched train presaturated TurboFLASH sequence at 7 T for the brain and heart.
To shorten the acquisition time of magnetization-prepared absolute transmit field (B1 + ) mapping known as presaturation TurboFLASH, or satTFL, to enable single breath-hold whole-heart 3D B1 + mapping. SatTFL is modified to remove the delay between the reference and prepared images (typically 5 T1 ), with matching transmit configurations for excitation and preparation RF pulses. The new method, called Sandwich, is evaluated as a 3D sequence, measuring whole-brain and gated whole-heart B1 + maps in a single breath-hold. We evaluate the sensitivity to B1 + and T1 using numerical Bloch, extended phase graph, and Monte Carlo simulations. Phantom and in vivo images were acquired in both the brain and heart using an 8-channel transmit 7 Tesla MRI system to support the simulations. A segmented satTFL with a short readout train was used as a reference. The method significantly reduces acquisition times of 3D measurements from 360 s to 20 s, in the brain, while simultaneously reducing bias in the measured B1 + due to T1 and magnetization history. The mean coefficient of variation was reduced by 81% for T1 s of 0.5-3 s compared to conventional satTFL. In vivo, the reproducibility coefficient for flip angles in the range 0-130° was 4.5° for satTFL and 4.7° for our scheme, significantly smaller than for a short TR satTFL sequence, which was 12°. The 3D sequence measured B1 + maps of the whole thorax in 26 heartbeats. Our adaptations enable faster B1 + mapping, with minimal T1 sensitivity and lower sensitivity to magnetization history, enabling single breath-hold whole-heart absolute B1 + mapping.


Anti-proliferative activity of hop-derived prenylflavonoids against human cancer cell lines.
Flavonoids form a substantial group of secondary plant metabolites that display several health-promoting effects. Therefore, prenylflavonoids, a subclass of flavonoids, have attracted increasing attention. Here, we investigated the possible anti-cancer potential of 6-prenylnaringenin (6-PN) and 8-prenylnaringenin (8-PN), two prenylflavonoids present in hops and beer and demonstrate an unexpectedly pronounced, dose-dependent reduction of cellular proliferation of human PC-3 prostate cancer and UO.31 renal carcinoma cells upon treatment. Based on these findings 6-PN and 8-PN are currently further clinically evaluated in detail.


Implant Placement in the Esthetic Zone: More Efficiency in Guided Surgery.
The aim of this case report is to describe the combination of a surgical guide with a temporary restoration to streamline the implant process. A 54-year-old male patient presenting with partial edentulism underwent computer-aided template-guided implant placement for the replacement of the missing upper second right incisor. The presented technique was used during the surgical procedures; it introduced the integration of a surgical guide into the temporary fixed partial denture. Using computer-aided design, computer-aided manufacturing technology and virtual implant planning, a temporary-implantation fixed partial denture was constructed, and a guidance sleeve was implemented into it. The implant bed preparation was then performed using the bridge as a surgical guide. After osteotomy, the guidance sleeve within the bridge was sealed, and the bridge was temporarily incorporated for submerged healing of the implant. The use of a temporary restoration as a surgical guide seems to make the digital workflow of guided implant placement more efficient by achieving a representative clinical outcome.


Unit activity in monkey parietal cortex related to haptic perception and temporary memory.
The neural responses of 456 single units were recorded in parietal cortex of behaving monkeys during a haptic delayed matching-to-sample task. (1) In areas 2 and 5 together, 22% of the neurons were activated by the auditory cue that signalled the beginning of a trial. Virtually all of these cells were also activated during the arm movements required by the task. These neurons, showing both auditory-related and movement-related responses, may function in sensorimotor integration. (2) Responses related to arm projection frequently began before movement onset, sometimes as much as 320 ms before. Such "premovement" responses were approximately equally common, and showed the same latency distribution, in areas 2, 5a, and 5b. (3) There was a topographic rostral-to-caudal gradient of decreasing neural responsiveness to the animal's manipulation of the cue (sample) objects. Eleven percent of manipulation-activated cells responded preferentially to one of the sample objects. (4) Many cells showed sustained (greater than 3 s) activation during the delay period (the time between handling of the sample object and palpation of the choice objects), even though at that time the monkey was sitting quietly and without stimulation. (5) Cells with sustained activation throughout most or all of the 18-s delay period were rare in all areas tested except area 5a. These cells, especially those that were preferentially activated depending on which sample object was palpated, may function in the temporary retention of haptic attributes. (6) The population of cells activated during sample manipulation was largely distinct from the population of cells showing sustained activation during the delay period. These two cell populations may represent different but complementary aspects of haptic perception. (7) The most common response during the delay period was sustained inhibition. This may be an expression of a nonspecific mechanism for decreasing background noise and enhancing neural responses to an anticipated perceptual event. (8) Relatively little evidence was found to support a functional distinction between the neural response properties of areas 2 and 5a. This suggests that area 2 may be at a higher level in the somatosensory hierarchy of the posterior parietal cortex than usually considered.


Carboxylesterases in the respiratory tracts of rabbits, rats and Syrian hamsters.
Esters are a widespread class of organic compounds found both in industry and the environment. Because esters are often volatile and, therefore, readily inhaled, the capacity of respiratory tract tissues as well as liver S-9 homogenates from rats, rabbits, and Syrian hamsters to hydrolyze a variety of esters was investigated. A new technique to determine hydrolysis rates by measuring carboxylic acid residues using ion chromatography was proven effective. The results indicated that esters, including potentially carcinogenic beta-lactones, are readily hydrolyzed by respiratory tract enzymes. Species and tissue differences were apparent. The nasal ethmoturbinates had especially high levels of esterase activity with tissue weight-normalized activities from rabbits and hamsters for most substrates exceeding all other tissues tested, including liver. Phenyl acetate was the most rapidly hydrolyzed by ethmoturbinate tissue of the esters tested. Among straight chain aliphatic alcohol acetates, hydrolysis rates increased with carbon number up to pentyl alcohol and then decreased. Branched 4-carbon alcohol acetates were less rapidly hydrolyzed than n-butyl acetate. Correlation of hydrophobicity constants with hydrolysis rates indicated that, for the straight chain aliphatic acetates, a bilinear model best fit the data.


Determining factors affecting public bike ridership and its spatial change before and after COVID-19.
COVID-19, which has spread since late 2019, has caused drastic changes in transportation use. A few studies have already addressed the relationships between COVID-19 and transportation mode choice. However, in most cases, the analysis has been based on transit ridership during the early phases of the COVID-19 pandemic. In addition, few studies have focused on public bike use before and after COVID-19. This study examines the effect of COVID-19 on the ridership of public bikes and various determining factors of public bike use. An origin-destination (OD) analysis and spatial regression models were used with public bike ridership data from Seoul, Korea. The findings of the analysis can be summarized as follows. First, this study confirms that public parks have significantly influenced the increase in public bike ridership since the COVID-19 outbreak. This finding indicates that outdoor spaces such as riverside parks have played important roles in public bike ridership during the pandemic period. Second, this study finds that accessibility to subway stations strongly impacts the increase in public bike ridership. This means that the demand for public bikes as a connected transportation mode has increased since COVID-19. Third, access to bike lanes has had a significant impact on the increase in public bike ridership. This finding indicates the importance of expanding the public bike infrastructure network. Finally, this study makes policy proposals to promote public bike ridership during the COVID-19 pandemic.


Molecular cloning, expression and characterization of a phenylalanine ammonia-lyase gene (SmPAL1) from Salvia miltiorrhiza.
Phenylalanine ammonia-lyase (PAL) is one of the branch point enzymes between primary and secondary metabolism. It plays an important role during plant development and defense. A PAL gene designated as SmPAL1 was cloned from Salvia miltiorrhiza using genome walking technology. The full-length SmPAL1 was 2,827 bp in size and consisted of an intron and two extrons encoding a 711-amino-acid polypeptide. Sequence alignment revealed that SmPAL1 shared more than 80% identity with the PAL sequences reported in Arabidopsis thaliana and other plants. The 5' flanking sequence of SmPAL1 was also cloned, and a group of putative cis-acting elements such as TATA box, CAAT box, G box and TC-rich repeats were identified. Transcription pattern analysis indicated that SmPAL1 expressed in all tissues examined, but more highly in leaf. Besides, expression of SmPAL1 was found to be induced by various treatments including ABA, wounding, and dehydration. To further confirm its function, SmPAL1 was expressed in Escherichia coli strain M15 with pQE-30 vector. The recombinant protein exhibited high PAL activity and could catalyze the conversion of L: -Phe to trans-cinnamic acid. This study will enable us to further understand the role SmPAL1 plays in the synthesis of active pharmaceutical compounds in S. miltiorrhiza at molecular level.


External fixation in the elderly.
Orthopaedic trauma is an increasingly common problem in geriatric patients. As demands of daily life and recreational activities are increasing in these patients, surgeons need to be able to manage geriatric fractures to achieve good functional results. Reduced bone quality in the elderly presents a considerable challenge and may preclude the use of established surgical stabilisation techniques that are performed in younger trauma patients. Furthermore, pre-existing medical conditions and considerable comorbidities in the elderly could complicate standard surgical procedures that younger patients would be offered. In this respect, application of external fixators represents a validated, minimally-invasive treatment opportunity. This review article summarises the use of external fixation in geriatric trauma patients for wrist fractures, proximal femoral fractures, pelvic fractures, and ankle fractures. Modern modifications, like pin coating with hydroxyapatite, and aspects of pin care will be discussed.