Short-term outcomes of micropulse transscleral laser therapy using the revised delivery probe in refractory glaucoma.
To evaluate the effectiveness of MicroPulse® transscleral laser therapy (MP-TLT) using both the original and revised MicroPulse P3® delivery probes in patients with refractory glaucoma. Retrospective study METHODS: We analyzed the data of patients with refractory glaucoma who underwent MP-TLT with the original and with the revised MicroPulse P3® Delivery Device from January 2018 to December 2020 at the University of Tokyo Hospital and who were followed up for 3 months. Patients' demographics, preoperative and postoperative intraocular pressure (IOP), medication scores, best-corrected visual acuity (BCVA), and complications were analyzed. This study enrolled 40 patients in both probe groups. At baseline, the mean IOP was 31.1 mmHg in the original group and 29.2 mmHg in the revised group, and it decreased to 22.6 mmHg and 21.6 mmHg after 3 months, respectively (paired t-test p=0.001, 0.001). No significant difference was noted between the number of medications and BCVA at baseline and 3 months in either probe group (paired t-test, p>0.05). Nor were any serious complications observed. MP-TLT using the revised MicroPulse P3® Delivery Device for the treatment of refractory glaucoma was effective in reducing IOP across glaucoma types with an excellent safety profile and was well-tolerated by the patients.


Antigenic analysis of H2 influenza virus haemagglutinin with monoclonal antibodies.
Antigenic analysis of human and avian H2 influenza virus was carried out with monoclonal antibodies to the HA molecules of H2 influenza viruses isolated in the early stage of an H2 pandemic. The study revealed antigenic differences between inhibitor sensitive (Japan+/57, RI+57) and inhibitor resistant strains (Japan-/57, Ri-/57). This indicates that the receptor-binding specificity of the haemagglutinin can markedly influence the antigenic analysis obtained with monoclonal antibodies in HI test. Minor antigenic differences (microheterogeneity) could be detected between different H2 influenza viruses isolated in 1957. Minor antigenic variation continued in the H2 viruses until 1961, but significant antigenic drift occurred in 1962 so that viruses isolated after that date reacted with few monoclonal antibodies. Analysis of avian H2 influenza viruses suggested antigenic differences between the different avian H2 haemagglutinin, but no correlation between the year of isolation and the progressive antigenic drift similar to that seen in the human strains was found.


Is there an association of regulatory region polymorphism in the alpha-1-antichymotrypsin gene with sporadic Alzheimer's disease in the northern Han-Chinese population?
Both invitro and invivo alpha-1-antichymotrypsin (ACT) directly inhibits amyloid beta peptide (Abeta) degradation and promotes Abeta deposition. However, whether the genetic variants in the regulatory region (including the promoter and the two enhancers) of the ACT gene affect susceptibility to Alzheimer's disease (AD) remains controversial. Here, we screened ACT promoter and enhancers in 244 patients with sporadic Alzheimer's disease (SAD) and 205 control patients, both of north Han-Chinese origin. Four single nucleotide polymorphisms (SNP) were found: (i) 11510T/C (rs10145747, named as ACT1); 11496G/A (rs4375593, ACT2); (iii) 11491T/C (rs4508366, ACT3); and (iv) 51G/T (rs1884082, ACT4). Neither individual SNP nor haplotypes were associated with AD onset. We concluded that the effect of the variations in the ACT regulatory region must be very limited, if occurring at all.


Hierarchically organization of biomineralized alginate beads for dual stimuli-responsive drug delivery.
Compartmentalized biomineralized alginate beads ranging from the micro to the visible scales with thermal- and pH-responsive drug delivery properties have been prepared via a one-step method in the present paper. Hollow multilayer microcapsules made of aliphatic poly(urethane-amine) (PUA) and sodium poly(styrenesulfonate) (PSS) serve as drug container to slow down the drug release. The results indicate that internal hollow multilayer microcapsules could hinder the permeation of the encapsulated Vitamin B2 (VB2) and retard the initial burst release of VB2. In addition, the drug release of compartmentalized biomineralized alginate beads exhibit distinguished pH- and thermal-dependent property due to pH-responsive alginate and the thermal-responsive aliphatic PUA. The drug release decreases when decreasing the pH value because the compact construction of alginate and biomineralized layer could prevent VB2 release from the beads. Moreover, the drug release is higher at 55 °C than that at 37 °C for the sake of the shrinkage of aliphatic PUA above its lower critical solution temperature (LCST). The results demonstrate that the compartmentalized biomineralized alginate beads show great potential as smart materials for controllable drug delivery.


Use of Doppler ultrasonography to detect an elusive communication of a spinal extradural arachnoid cyst.
Spinal extradural arachnoid cysts are thought to be extradural arachnoid pouches that communicate with the intraspinal subarachnoid space through a small dural defect. The mainstay of current treatment is resection of the cyst wall followed by obliteration of the communicating pedicle. Despite its clinical importance, the communicating pedicle of the cyst is often elusive. The authors report a 57-year-old woman with an extradural arachnoid cyst with intractable back pain and progressive motor weakness. Preoperative imaging studies, including phase-contrast MRI, failed to identify the communicating pedicle. Intraoperative Doppler ultrasonography clearly demonstrated the pulsatile influx of cerebrospinal fluid into the cyst. A flap-like structure was also noted near the pedicle; this structure appeared to act as a one-way valve. Doppler ultrasonography may be a helpful adjunct for identifying the location of elusive communication in a spinal extradural arachnoid cyst.


Erratum: Comparative Study of Auto Plan and Manual Plan for Nasopharyngeal Carcinoma Intensity-Modulated Radiation Therapy [Corrigendum].
[This corrects the article DOI: 10.2147/CMAR.S226495.].


Sarcopenia is related to poor prognosis in patients after trimodality therapy for locally advanced non-small cell lung cancer.
The association between sarcopenia and prognosis in patients with locally advanced non-small cell lung cancer (NSCLC) undergoing trimodality therapy, consisting of preoperative concurrent chemoradiotherapy and surgery, has not been reported. Therefore, we aimed to investigate the association of sarcopenia and fat mass with prognosis after trimodality therapy. To assess sarcopenia, the psoas muscle mass was measured. Using computed tomography data, including third lumbar vertebra level images, psoas muscle mass and visceral and subcutaneous fat mass were measured. Additionally, body mass indices, and visceral/subcutaneous fat ratio, obtained by dividing the visceral fat index by the subcutaneous fat index, were calculated. We investigated the relationship between these parameters and overall survival. Ninety-nine eligible patients were included. In the univariate analysis, age, clinical stage, tumor location, psoas muscle index, and visceral/subcutaneous fat ratio were significant prognostic factors for overall survival (P = 0.008, P = 0.04, P = 0.04, P = 0.02, and P = 0.02, respectively). In the multivariate analysis, age and psoas muscle index were significant prognostic factors for overall survival (P = 0.01 and P = 0.03, respectively). The 5-year overall survival rates for the high and low psoas muscle index groups were 79.6% [95% confidence interval (CI), 67.1-94.5%] and 66.2% (95% CI, 54.1-81.1%), respectively; whereas, the 10-year overall survival rates were 61.9% (95% CI, 42.0-91.4%) and 25.3% (95% CI, 8.6-74.2%), respectively. Sarcopenia was related to poor overall survival in patients with locally advanced NSCLC undergoing trimodality therapy. Assessment of body composition prior to treatment may provide important information for formulating rational therapeutic strategies.


Pavlovian conditioning with proximal stimuli.
This experiment was conducted with the objective of demonstrating that the effective stimuli in Pavlovian Conditioning are not environmental stimuli but internal physiological processes elicited by environmental input (proximal stimuli). In order to achieve the objective, afterimages in color vision were used: looking at a diffuse lightened circle after seeing a red circle yields an image of a green circle. A differential conditioning paradigm with two sequential compounds was run. In one group (G+B-: n1 = 10), a red circle followed by a green circle was paired with shock, whereas a red circle followed by a blue circle remained unpaired. A second group (G-B+: n2 = 10) received red-blue paired trials and unpaired red-green trials. Immediately after that training, subjects were tested with a new, never trained sequential compound: a red circle followed by a diffuse lightened circle. Furthermore, they were tested with the already trained compounds. Taking the environmental point of view, the never trained stimulus should elicit an orienting response lying in between the excitatory reaction to the paired stimulus and the inhibitory reaction to the unpaired stimulus. From the proximal point of view, the diffuse light should elicit an excitatory reaction in group G+B- and an inhibitory reaction in group G-B+. Electrodermal conditioned anticipatory and omission responses were measured. The results supported the proximal hypothesis. Hence, defining input in environmental terms may be the wrong way. Instead, in conceptualizing the stimulus in conditioning, the following should be considered: the processing organism itself is creating the effective stimuli.


Prevalence of overuse injuries in athletes from individual and team sports: A systematic review with meta-analysis and GRADE recommendations.
Overuse injuries result from the cumulative process of repetitive microtrauma and overload on the musculoskeletal system, which causes tissue damage. Therefore, these injuries may have long-term negative consequences that decrease an athlete's performance. To estimate the prevalence of overuse injuries in individual and team sports. Searches on MEDLINE, EMBASE, SPORTDiscus, and CINAHL from the first registration to February 2021 and hand-searching identified studies investigating the prevalence of overuse injuries in athletes from individual and team sports. Meta-analysis was conducted and the GRADE system summarized the overall quality of evidence. This review was registered in PROSPERO (CRD42019135665). Seventeen studies were included and pooling of 24 704 participants (22 748 of individual sports and 1.956 of team sports). Data from point- and period-prevalence of overuse injuries in individual and team sports were obtained. Pooled period-prevalence of overuse injuries in individual and team sports was 42.0% (95% CI: 30.0, 55.0) and 33.0% (95% CI: 21.0, 49.0), respectively. Another four studies investigated point-prevalence. The overall quality of evidence for the period-prevalence was of moderate quality. Sensitivity analyses suggested that different joints based in individual and team sports tended to increase the estimated prevalence of overuse injuries. Athletes, clinicians, sport teams, and policymakers should be aware of the high prevalence of overuse injuries in athletes, especially, in athletes from individual sports. Current moderate-quality evidence shows that future high-quality studies are likely to impact on the estimated prevalence.


A 17q12 chromosomal duplication associated with renal disease and esophageal atresia.
Chromosomal imbalance of the 17q12 region (which includes the HNF1B transcription factor) has recently emerged as a frequent condition. 17q12 deletion was found in patients with various renal abnormalities, diabetes mellitus (MODY type 5), genital tract or liver test abnormalities, while 17q12 duplication was identified in a subset of patients with autism, mental retardation, epilepsy and/or schizophrenia but no renal disorder. We report here two first-degree relatives carrying a 17q12 duplication and harboring various renal abnormalities (bilateral hypoplastic kidneys with vesico-ureteric reflux or multicystic dysplatic kidney with contralateral hyperechogenic kidney). Esophageal atresia (EA) type C was identified at birth in one patient while none had neurological disorder. Because EA has already been identified in patients with 17q12 duplication or HNF1B point mutation, we screened HNF1B (QMPSF and direct sequencing) in nine additional patients with EA and renal abnormalities but failed to identify any pathogenic variant. This is the second report of HNF1B mutation associated with EA. Moreover, we showed herein, that renal malformations may be part of the 17q12 duplication syndrome.


Modified glutinous rice starch-chitosan composite films for buccal delivery of hydrophilic drug.
The fabrication and characterization of ball-milling modified glutinous rice starch (MGRS):chitosan (CS) composite films were demonstrated. Effect of CS ratios (2:1, 1:1, 1:2 MGRS:CS) on the film properties was investigated. Lidocaine hydrochloride was used as a model hydrophilic drug. ATR-FTIR confirmed hydrogen bond formation between MGRS and CS. XRD indicated an amorphous state of all fabricated films. The uniform and comparable thickness, weight, and drug contents of all fabricated films were obtained. The presence of CS did not affect the mucoadhesiveness of MGRS films. The increase in tensile strength and decreases in elongation and folding endurance were observed with 1:2 MGRS:CS films. The film swelling and drug release decreased with the CS ratio. Drug permeation across porcine mucosa indicated the enhancement effect of CS, whereby the permeation flux of 1:2 MGRS:CS composite increased by 3 folds. In conclusion, the MGRS:CS composite could be useful for buccal delivery of hydrophilic drug.


Representatives of generation 'Z' as future doctors - results of research among final year students at medical universities in Poland.
The nature of the work of doctors is inseparable from responsibility for human health and life, exposure to many risk factors related to physical, chemical, biological and psychosocial risks, as well as the specificity of the organization of the health care system in Poland. This prompted the authors to ask future doctors, currently students of the penultimate and the final year of medical studies, questions about what is important to them in their future profession and how studies at the medical universities met these needs. Identification of skills important for future doctors to perform their profession was conducted in the third quarter of 2020 in the form of an online diagnostic survey on a sample of 442 fifth- and sixth-year medicine students at medical universities in Poland. The study shows that most students graduating in medicine are satisfied with their choice and intend to work in the profession they have learned. In this study, the responders, on average, felt well prepared theoretically for their future profession, whereas when indicating their practical preparedness, it was much lower. One of the most important skills indicated by students participating in this study was communication with patients. Overall, the quality of medical studies in Poland is rated very high by the students. Nevertheless, there is a lack of or insufficient time spent on teaching and helping future doctors develop soft skills; therefore, more focus should be placed on this aspect of studies.


Effectiveness of web-based feedback interventions for people with overweight and obesity: systematic review and network meta-analysis of randomized controlled trials.
Web-based delivered interventions have become an innovative option to treat health problems, like obesity. The aim of this systematic review and network meta-analysis was to analyze the effectiveness of web-based behavioral treatments for adults with overweight and obesity. Web-based interventions and comparison interventions (traditional weight control programs) were classified according to the following feedback characteristics: frequency, personalization, and provider (human versus machine). From the initial 1789 studies, 15 were included in this review. A network meta-analysis was conducted to analyze the efficacy of web-based programs with traditional interventions, considering direct and indirect comparisons. The main outcome was the weight loss mean difference (kg) between baseline and post-treatment. Heterogeneity and consistency assumptions were validated to conduct the network meta-analysis. Network meta-analysis showed comparisons between different treatment options. The main results were that Intensive Contact Web-based programs were more effective than wait-list (Mean Difference - 1.86 kg; 95% Confidence Interval: - 3.61, - 0.12). Moreover, Intensive Contact Web-based programs were more effective than the other web-based options and self-help traditional interventions. However, the only significant comparison was Intensive Contact Web-based programs versus Guided Self-Help Web-based programs (Mean Difference - 4.31 kg; 95% Confidence Interval: - 5,22, - 3,41). Intensive Contact Web-based programs were the most effective treatment option according the obtained results, achieving the first place in the ranking provided by the network meta-analysis with 98.5% of probabilities. Intensive Contact Web-based interventions have obtained the first position in the ranking, proving the relevance of frequent, personalized, and professional feedback and their association with a better prognosis for people with overweight and obesity. These results provide relevant information to design more effective treatments for people with overweight and obesity, in a new format especially appropriate for the current situation.


Nicotinic mechanisms in the treatment of psychotic disorders: a focus on the α7 nicotinic receptor.
Nicotine is heavily abused by persons with schizophrenia. Nicotine better enables people with schizophrenia to filter out extraneous auditory stimuli. Nicotine also improves prepulse inhibition when compared to placebo. Nicotine similarly increases the amplitude of patients' duration mismatch negativity. The 15q13-14 region of the genome coding for the α7 nicotinic receptor is linked to schizophrenia. Multiple single nucleotide polymorphisms have been identified in this 15q13-14 gene promoter region that are more frequently present in people with schizophrenia than in normal controls. Abnormalities in expression and regulation of central nicotinic cholinoceptors with decreased α7 binding in multiple brain regions are also present. Nicotine enhances cognition in schizophrenia. Alternative agents that activate the nicotinic receptor have been tested including 3-[2,4-dimethoxybenzylidene]anabaseine (DMXB-A). This compound improved attention, working memory, and negative symptoms in an add-on study in nonsmoking patients with schizophrenia. There are multiple other nicotinic agents, including positive allosteric modulators, in the preclinical stages of development. Finally, the effects of varenicline and clozapine and their relation to smoking cessation are discussed.


Reversal of the anti-implantational effect of luteinizing hormone-releasing hormone (LRH) by estradiol-17 beta and progesterone, alone and in sequence.
The use of estradiol-17 beta and progesterone, alone or in sequence, to reverse the anti-implantational effect of 100 and 500 micrograms LRH has been studied. Sequential administration of the steroids was most efficacious in reversing the effect of 100 micrograms while progesterone alone proved to be the only treatment inhibiting the effect of 500 micrograms LRH. A possible difference in mechanism of action of the two doses of LRH is discussed.


Leishmania in the Old World: 3. The distribution of L. aethiopica zymodemes.
Isoenzyme profiles of 28 stocks of Leishmania aethiopica were compared with those of reference strains of L. aethiopica, L. tropica and L. major using starch-gel electrophoresis of 13 enzymes (GPI, GD, ES, PGM, PEPD, NH, ASAT, ALAT, PK, MPI, 6PGD, SOD, MDH). 13 zymodemes were seen. L. aethiopica showed some infraspecific variation. Stocks from Phlebotomus longipes and Procavia habessinica were indistinguishable from those from man. Stocks from cases of diffuse cutaneous and cutaneous leishmaniasis were indistinguishable. Only one enzyme pattern was held in common with the L. tropica reference strain enzyme profile, and none with the L. major reference strain. The status of L. aethiopica as a separate species is supported.


iUbiq-Lys: prediction of lysine ubiquitination sites in proteins by extracting sequence evolution information via a gray system model.
As one of the most important posttranslational modifications (PTMs), ubiquitination plays an important role in regulating varieties of biological processes, such as signal transduction, cell division, apoptosis, and immune response. Ubiquitination is also named "lysine ubiquitination" because it occurs when an ubiquitin is covalently attached to lysine (K) residues of targeting proteins. Given an uncharacterized protein sequence that contains many lysine residues, which one of them is the ubiquitination site, and which one is of non-ubiquitination site? With the avalanche of protein sequences generated in the postgenomic age, it is highly desired for both basic research and drug development to develop an automated method for rapidly and accurately annotating the ubiquitination sites in proteins. In view of this, a new predictor called "iUbiq-Lys" was developed based on the evolutionary information, gray system model, as well as the general form of pseudo-amino acid composition. It was demonstrated via the rigorous cross-validations that the new predictor remarkably outperformed all its counterparts. As a web-server, iUbiq-Lys is accessible to the public at http://www.jci-bioinfo.cn/iUbiq-Lys . For the convenience of most experimental scientists, we have further provided a protocol of step-by-step guide, by which users can easily get their desired results without the need to follow the complicated mathematics that were presented in this paper just for the integrity of its development process.


Utility of conventional clinical risk scores in a low-risk COVID-19 cohort.
Several specific risk scores for Coronavirus disease 2019 (COVID-19) involving clinical and biochemical parameters have been developed from higher-risk patients, in addition to validating well-established pneumonia risk scores. We compared multiple risk scores in predicting more severe disease in a cohort of young patients with few comorbid illnesses. Accurately predicting the progression of COVID-19 may guide triage and therapy. We retrospectively examined 554 hospitalised COVID-19 patients in Singapore. The CURB-65 score, Pneumonia Severity Index (PSI), ISARIC 4C prognostic score (4C), CHA2DS2-VASc score, COVID-GRAM Critical Illness risk score (COVID-GRAM), Veterans Health Administration COVID-19 index for COVID-19 Mortality (VACO), and the "rule-of-6" score were compared for three performance characteristics: the need for supplemental oxygen, intensive care admission and mechanical ventilation. A majority of patients were young (≤ 40 years, n = 372, 67.1%). 57 (10.3%) developed pneumonia, with 16 (2.9% of study population) requiring supplemental oxygen. 19 patients (3.4%) required intensive care and 2 patients (0.5%) died. The clinical risk scores predicted patients who required supplemental oxygenation and intensive care well. Adding the presence of fever to the CHA2DS2-VASc score and 4C score improved the ability to predict patients who required supplemental oxygen (c-statistic 0.81, 95% CI 0.68-0.94; and 0.84, 95% CI 0.75-0.94 respectively). Simple scores including well established pneumonia risk scores can help predict progression of COVID-19. Adding the presence of fever as a parameter to the CHA2DS2-VASc or the 4C score improved the performance of these scores in a young population with few comorbidities.


Overcoming Voltage Losses in Vanadium Redox Flow Batteries Using WO3 as a Positive Electrode.
Vanadium redox flow batteries (VRFBs) are appealing large-scale energy storage systems due to their unique properties of independent energy/power design. The VRFBs stack design is crucial for technology deployment in power applications. Besides the design, the stack suffers from high voltage losses caused by the electrodes. The introduction of active sites into the electrode to facilitate the reaction kinetic is crucial in boosting the power rate of the VRFBs. Here, an O-rich layer has been applied onto structured graphite felt (GF) by depositing WO3 to increase the oxygen species content. The oxygen species are the active site during the positive reaction (VO2 +/VO2+) in VRFB. The increased electrocatalytic activity is demonstrated by the monoclinic (m)-WO3/GF electrode that minimizes the voltage losses, yielding excellent performance results in terms of power density output and limiting current density (556 mWcm-2@800 mAcm-2). The results confirm that the m-WO3/GF electrode is a promising electrode for high-power in VRFBs, overcoming the performance-limiting issues in a positive half-reaction.


Effect of psyllium and gum Arabic biopolymers on the survival rate and storage stability in yogurt of Enterococcus duransIW3 encapsulated in alginate.
Different herbal biopolymers were used to encapsulate Enterococcus durans IW3 to enhance its storage stability in yogurt and subsequently its endurance in gastrointestinal condition. Nine formulations of encapsulation were performed using alginate (ALG), ALG-psyllium (PSY), and ALG-gum Arabic (GA) blends. The encapsulation efficiency of all formulations, tolerance of encapsulated E. durans IW3 against low pH/high bile salt concentration, storage lifetime, and release profile of cells in natural condition of yogurt were evaluated. Result revealed 98.6% encapsulation efficiency and 76% survival rate for all formulation compared with the unencapsulated formulation cells (43%). The ALG-PSY and ALG-GA formulations have slightly higher survival rates at low pH and bile salt condition (i.e., 76-93% and 81-95%, respectively) compared with the ALG formulation. All encapsulated E. durans IW3 was released from the prepared beads of ALG after 90 min, whereas both probiotics encapsulated in ALG-GA and ALG-PSY were released after 60 min. Enterococcus durans IW3 was successfully encapsulated in ALG, ALG-GA, and ALG-PSY beads prepared by extrusion method. ALG-GA and ALG-PSY beads are suitable delivery carriers for the oral administration of bioactive compounds like probiotics. The GA and PSY gels exhibited better potential for encapsulation of probiotic bacteria cells because of the amendment of ALG difficulties and utilization of therapeutic and prebiotic potentials of these herbal biopolymers.


Carcinoma of the nasal cavity and paranasal sinuses: an analysis of radical radiotherapy.
A retrospective analysis was conducted of 152 patients with carcinoma of the nasal cavity and paranasal sinuses who were treated with radical radiotherapy between 1975-1984. Stages at presentation were T1 11%, T2 18%, T3 27%, and T4 44%. The median follow-up was 61 months. The overall corrected 5-year survival was 47% and by T stage, T1 86%, T2 82%, T3 49%, T4 25%. Local control was achieved in 45% of cases following radiotherapy. Salvage surgery was attempted in 20 patients where radiotherapy failed and was successful in eight. Nodal disease was present in 6.5% of patients at presentation and 10.5% developed nodal disease after treatment. Nodal disease as sole relapse occurred in four patients and was associated with prolonged survival following radical salvage treatment. Distant metastatic disease occurred in 25 patients and of these 17 (68%) also had locoregional failure. Osteoradionecrosis occurred in three cases, and a further three cases developed bilateral blindness. We conclude that radical radiotherapy achieves results comparable to published data for combined surgery and radiotherapy with acceptable toxicity.


Sensitivity to methacholine and capsaicin in patients with unclear respiratory symptoms.
Capsaicin, the pungent ingredient in red pepper, is known to stimulate coughing via the sensory nervous system. Earlier studies showed that patients with airway symptoms induced by chemicals and strong scents cough more after inhalation of capsaicin than healthy control subjects and this has been interpreted as a hyperreactivity of airway sensory nerves. Our aim was to study airway sensitivity to inhaled capsaicin and the occurrence of airway symptoms induced by strong scents in patients who underwent a bronchial methacholine test, primarily because of suspected asthma. Fifty-two consecutive patients referred for testing with methacholine were also provoked with inhaled capsaicin in increasing concentrations. Cough sensitivity to capsaicin was compared with that in 40 healthy control subjects. The patients coughed significantly more compared with the healthy control subjects with each dose of capsaicin (P < 0.0001). Twelve patients (23%) had a positive methacholine test, and of these, nine were diagnosed with asthma. There was no difference in capsaicin sensitivity between patients sensitive or insensitive to methacholine. The majority of the patients had no increased sensitivity to methacholine but did demonstrate sensory hyperreactivity (SHR). SHR appears to be a common diagnosis in investigations of patients with obscure airway symptoms.


Medical treatment of Meniere's disease.
The aim of this article is to review the pharmacologic therapy used in the treatment of Meniere's disease. The first portion of the article discusses the treatment of acute labyrinthine crisis, which includes medication for patients that provides relief of the nausea, vomiting, and vertigo that accompanies acute attack. The second half of the article discusses medication used to help prevent attacks of Meniere's disease.


Massive iron accumulation in PKAN-derived neurons and astrocytes: light on the human pathological phenotype.
Neurodegeneration associated with defective pantothenate kinase-2 (PKAN) is an early-onset monogenic autosomal-recessive disorder. The hallmark of the disease is the massive accumulation of iron in the globus pallidus brain region of patients. PKAN is caused by mutations in the PANK2 gene encoding the mitochondrial enzyme pantothenate kinase-2, whose function is to catalyze the first reaction of the CoA biosynthetic pathway. To date, the way in which this alteration leads to brain iron accumulation has not been elucidated. Starting from previously obtained hiPS clones, we set up a differentiation protocol able to generate inhibitory neurons. We obtained striatal-like medium spiny neurons composed of approximately 70-80% GABAergic neurons and 10-20% glial cells. Within this mixed population, we detected iron deposition in both PKAN cell types, however, the viability of PKAN GABAergic neurons was strongly affected. CoA treatment was able to reduce cell death and, notably, iron overload. Further differentiation of hiPS clones in a pure population of astrocytes showed particularly evident iron accumulation, with approximately 50% of cells positive for Perls staining. The analysis of these PKAN astrocytes indicated alterations in iron metabolism, mitochondrial morphology, respiratory activity, and oxidative status. Moreover, PKAN astrocytes showed signs of ferroptosis and were prone to developing a stellate phenotype, thus gaining neurotoxic features. This characteristic was confirmed in iPS-derived astrocyte and glutamatergic neuron cocultures, in which PKAN glutamatergic neurons were less viable in the presence of PKAN astrocytes. This newly generated astrocyte model is the first in vitro disease model recapitulating the human phenotype and can be exploited to deeply clarify the pathogenetic mechanisms underlying the disease.


Effect of total parenteral nutrition with different lipid emulsions of human monocyte and neutrophil functions.
Parenteral nutrition (TPN) with lipid emulsions is claimed to be associated with impaired monocyte (M) and neutrophil (N) functions. Long-chain triglycerides (LCT) and a mixture containing 50% medium-chain triglycerides (MCT) and 50% LCT, currently used in nutritional therapy with TPN, were evaluated for their ex vivo effects on human N and M chemotaxis, phagocytosis, bacterial killing, and oxidative metabolism by nitroblue tetrazolium reduction test. Cell functions were examined in a randomized, crossover, blind trial in 10 malnourished patients with gastric cancer. Prior to the operation (2 wk), central TPN (40 kcal/kg) with 25% of caloric energy provided as LCT or MCT/LCT emulsion was infused over 48 h. After the crossover period fat-free TPN was given over 48 h. Function tests were done for N and M before and after each lipid emulsion infusion. Every cell function test performed for each patient was controlled by another test done in healthy adult volunteers and the results were compared with the normal range of values previously established for a healthy adult population. All the patients completed the studies without complications. Crossover validity was statistically established. Bacterial killing was the only function reduced in neutrophils after LCT emulsion (% killed bacteria = 79.0 +/- 8.5 versus 67.4 +/- 19.2; P < 0.05), although this function remained within the normal range values in 80% of the patients. In conclusion, the lipid emulsions did not affect any monocyte functions and only moderately decreased neutrophil bacterial killing.


ADP is the dominant controller of AMP-activated protein kinase activity dynamics in skeletal muscle during exercise.
Exercise training elicits profound metabolic adaptations in skeletal muscle cells. A key molecule in coordinating these adaptations is AMP-activated protein kinase (AMPK), whose activity increases in response to cellular energy demand. AMPK activity dynamics are primarily controlled by the adenine nucleotides ADP and AMP, but how each contributes to its control in skeletal muscle during exercise is unclear. We developed and validated a mathematical model of AMPK signaling dynamics, and then applied global parameter sensitivity analyses with data-informed constraints to predict that AMPK activity dynamics are determined principally by ADP and not AMP. We then used the model to predict the effects of two additional direct-binding activators of AMPK, ZMP and Compound 991, further validating the model and demonstrating its applicability to understanding AMPK pharmacology. The relative effects of direct-binding activators can be understood in terms of four properties, namely their concentrations, binding affinities for AMPK, abilities to enhance AMPK phosphorylation, and the magnitudes of their allosteric activation of AMPK. Despite AMP's favorable values in three of these four properties, ADP is the dominant controller of AMPK activity dynamics in skeletal muscle during exercise by virtue of its higher concentration compared to that of AMP.


Lupiwighteone induces caspase-dependent and -independent apoptosis on human breast cancer cells via inhibiting PI3K/Akt/mTOR pathway.
Breast cancer is one of the most common causes of mortality in women. Lupiwighteone has anticancer effects in prostate cancer cells and neuroblastoma cells. However, the molecular and cellular mechanisms of lupiwighteone effects on human breast cancer cells are not as well known. In the present study, we investigated the effects of lupiwighteone on the proliferation and apoptosis of two different human cancer cells; MCF-7, an estrogen receptor (ER)-positive human breast cancer cell, and MDA-MB-231, a triple negative human breast cancer cell. Lupiwighteone treatment decreased the viability of MCF-7 and MDA-MB-231 cells. Lupiwighteone treatment resulted in apoptotic cell death in breast cancer cells, which was characterized by DNA fragmentation, accumulation of apoptotic cells, and nuclear condensation. We also showed that treatment with lupiwighteone induced caspase-dependent apoptosis (up-regulation of caspase-3, -7, -8, -9, PARP, and Bax or down-regulation of Bid, Bcl-2), induction of caspase-independent apoptosis (up-regulation of AIF and Endo G on cytosol), and inhibition of the PI3K/Akt/mTOR signaling pathway (down-regulation of PI3K, p-Akt, and p-mTOR) in both MCF-7 and MDA-MB-231 cells. These results suggest that lupiwighteone induces caspase-dependent and -independent apoptosis in both breast cancer cell lines via inhibiting PI3K/Akt/mTOR pathway.


Chalcogenatetrasilacyclopentenes: Five-Membered Rings with Endocyclic Si-Si Double Bonds.
The formal [4+1] cycloaddition of the chalcogens S, Se, and Te to the tetrasilabuta-1,3-diene 1 furnishes the molecules 2-4, the first five-membered rings with endocyclic Si-Si double bonds. The new compounds are thermally stable and chemically inert. However, 4 is light-sensitive and decomposes in daylight with deposition of tellurium. R=2,4,6-iPr3C6H2.


Placenta praevia without antepartum haemorrhage.
The incidence of placenta praevia praevia in a series in a series of 26,155 patients was 0.9%; in 81 of the 238 patients (34%) there was no antepartum haemorrhage. Placenta praevia was known to be present before delivery in only 12 of the latter group, the condition being diagnosed after vaginal delivery in 17 and at Caesarean section in 52. Approximately 40% of patients with placenta praevia who deliver vaginally have had no antepartum haemorrhage.


Effects of probucol on the composition and in vitro catabolism of LDL in type IIa hypercholesterolemia.
A possible mechanism of action of probucol on low density lipoprotein uptake was examined in 7 type IIa hypercholesterolemic subjects. Probucol administration effectively lowered plasma cholesterol. Both apo B-associated cholesterol and HDL cholesterol were decreased but a great inter-patient variability was noted. Plasma triglycerides were unchanged and phospholipids decreased. The composition of the isolated LDL was unaffected. The LDL displaceable activity of reference [125I]LDL measured by competition assays in control fibroblasts, was increased in 3 subjects, decreased in 1 subject and unchanged in the other 3. No correlation was found between the change in apo B-associated cholesterol and the change in the in vitro catabolism of LDL of treated patients. The results did not allow a simple mechanism of action to be ascribed to the drug, but questioned the origin of the hypercholesterolemia.


Net clinical benefit of clopidogrel versus ticagrelor in elderly patients carrying CYP2C19 loss-of-function variants with acute coronary syndrome after percutaneous coronary intervention.
Elderly patients with acute coronary syndrome (ACS) tend to choose clopidogrel over potent P2Y12 receptor inhibitor such as ticagrelor after percutaneous coronary intervention (PCI) in China considering higher risks of bleeding. CYP2C19 genotype is regarded as a major factor influencing the efficacy of clopidogrel. The present study aims to investigate the efficacy and safety of ticagrelor relative to clopidogrel in elderly ACS patients after PCI in China with reduced CYP2C19 metabolism. Between January 2016 and March 2019, 2751 ACS patients over 65 years old with CYP2C19 loss-of-function (LOF) variants after PCI were enrolled. All patients were treated with aspirin and P2Y12 receptor inhibitor, among whom 2056 received clopidogrel and 695 received ticagrelor. Net adverse clinical events (NACE), a composite of cardiac death, myocardial infarction (MI), ischemic stroke, target vessel revascularization and clinically relevant bleeding including Bleeding Academic Research Consortium (BARC) types 2, 3, 5 bleeding, were compared between the two groups at 12 months after PCI. Propensity score matching (PSM) was conducted to balance the baseline characteristics between the two groups. Before and after PSM, NACE was significantly increased in ticagrelor group compared with clopidogrel group at 12 months post PCI (Before PSM, 15.18% vs. 25.61% p<0.001; After PSM, 11.66% vs. 26.01% p<0.001). MACE was comparable between the two groups (Before PSM, 5.45% vs. 5.32% p>0.999; After PSM, 3.59% vs. 5.38% p=0.146). BARC types 2, 3, 5 bleeding events were significantly increased in patients treated with ticagrelor relative to clopidogrel (Before PSM, 10.31% vs. 21.01% p<0.001; After PSM, 8.22% vs. 21.38% p<0.001), which was mainly attributed to a higher incidence of BARC type 2 bleeding events in ticagrelor group (Before PSM, 8.12% vs. 18.56% p<0.001; After PSM, 6.43% vs. 18.83% p<0.001). In the present real-world study, selection of ticagrelor over clopidogrel showed a significant increase in NACE with a higher incidence of bleeding and similar ischemic events in elderly ACS patients carrying CYP2C19 LOF variants after PCI.


Morphological and molecular characterization of Isospora amphiboluri (Apicomplexa: Eimeriidae), a coccidian parasite, in a central netted dragon (Ctenophorus nuchalis) (De Vis, 1884) in Australia.
An Isospora species, Isospora amphiboluri, originally described by Canon in 1967 and later by McAllister et al. (1995), was isolated from a central netted dragon (Ctenophorus nuchalis) housed at a wildlife rehabilitation centre in Perth, Western Australia. Sporulated oocysts of Isospora amphiboluri (n = 30) are spherical, 24.2 (26.5-23.0) μm in length and 23.9 (22.4-25.9) μm in width, with a shape index of 1.01. The bilayered oocyst wall is smooth and light-yellow in color. Polar granule, oocyst residuum and micropyle are absent. The sporocysts are lemon-shaped, 15.7 (15.2-18.0) × 10.2 (8.9-11.2) μm, with a shape index (length/width) of 1.53. Stieda and substieda bodies are present, the Stieda body being small and hemidome-shaped and the substieda half-moon-shaped. Each sporocyst contains four vermiform sporozoites arranged head to tail. The sporozoites are 11.7 (9.9-16.2) × 3.0 (2.4-3.5) μm, with a shape index (length/width) of 3.87. A sporocyst residuum is present. Sporozoites contain a central nucleus with a finely distributed granular residuum. Comparison of oocyst measurements and their features with other valid Isospora species from hosts in the Agamid family confirmed that this Isospora species is Isospora amphiboluri. Molecular characterization of I. amphiboluri at the 18S rRNA and MTCOI loci showed the highest similarity with I. amphiboluri from the central bearded dragon, 99.8% and 99.7% respectively. This is the first report of I. amphiboluri from a central netted dragon in Australia.


[Pre-implantation surgery of the atrophied maxilla. A review of the literature].
The aim of preprosthetic reconstructive surgery of the resorbed maxilla is to create sufficient bone of good quality for implant placement. The classification of the edentulous jaws by Cawood and Howell is mostly used as point of departure in planning preprosthetic reconstructive surgery. In this review article some procedures and results are mentioned as described in recent literature.


Non-surgical management of tooth hypersensitivity.
It would appear that toothpastes containing arginine and calcium carbonate (for example Colgate® Sensitive Pro-Relief™) are particularly effective at managing tooth sensitivity.


History of allergies among adults with glioma and controls.
The causes of most adult gliomas are essentially unknown. Previous studies have indicated associations between immune system factors and the incidence of adult glioma, specifically that those individuals with certain allergic conditions may have decreased risk of glioma. We obtained detailed allergy histories for 405 adults newly diagnosed with glioma in the San Francisco Bay Area from 1997-1999 and 402 age-gender-ethnicity frequency-matched population-based controls. Seventy-nine percent of eligible cases or their proxies and 74% of eligible controls completed in-person interviews about allergies, age at onset, frequency, duration and severity. Overall, cases were less likely than controls to report any allergy (72% vs. 85%; odds ratio [OR] = 0.5 [0.3-0.7]); for self-reported cases (n = 269), OR = 0.7 (0.4-0.97) and for proxy-reported cases, OR = 0.3 (0.2-0.5). Pollen, dairy and nut allergies were significantly less common in cases than controls and most other allergens had odds ratios of less than one. There were no apparent trends with numbers of symptoms, route of exposure of allergen or reported severity of allergy, but there was a significant dose-response with increasing numbers of allergens (p < 0.0001 for linear trend among all cases vs. controls and p = 0.02 among self-reported cases only vs. controls). Although our work displays strong and consistent associations, future efforts must attempt to establish whether an immune system typified by proclivity to allergies, or an immunologic consequence of the allergies themselves, might be capable of preventing nascent brain tumors. The dominance of humoral immunity in the central nervous system is consistent with either of these models. Alternatively, common genetic or environmental causes for allergies and gliomagenesis may mediate or confound these observed inverse risks for allergies and gliomas, or other explanations may exist. Future work might reveal an important role for immunologic factors in gliomagenesis and potential preventative and/or therapeutic modalities.


Successful balloon-occluded retrograde transvenous obliteration for gastric varix mainly draining into the pericardiophrenic vein.
Two cases of gastric varices were treated by balloon-occluded retrograde transvenous obliteration via the pericardiophrenic vein at our hospital, and both were successful. One case developed left hydrothorax. Gastric varices did not bled and esophageal varices were not aggravated in both cases for 24-30 months thereafter. These outcomes indicate the feasibility of balloon-occluded retrograde transvenous obliteration via the pericardiophrenic vein.


Effect of a group-based acceptance and commitment therapy (ACT) intervention on self-esteem and psychological flexibility in patients with schizophrenia in remission.
The present study explored whether acceptance and commitment therapy (ACT), a cognitive behavioral therapy approach, could improve the symptoms of schizophrenia spectrum disorders among patients with schizophrenia in remission. A pre- and post-treatment design with two evaluation time points was employed. Sixty outpatients with schizophrenia in remission were randomly divided into two groups: the ACT plus treatment as usual (ACT+TAU) and treatment as usual (TAU) groups. The ACT+TAU group participated in 10 group-based ACT interventions and TAU in the hospital, and the TAU group only received TAU interventions. General psycho-pathological symptoms, self-esteem, and psychological flexibility were assessed before intervention (baseline; pre-test) and after intervention (five weeks; post-test). Results indicated that, compared to the TAU group, the ACT+TAU group exhibited a more significant improvement in general psychopathological symptoms, self-esteem, cognitive fusion, and acceptance and action at post-test. ACT intervention could effectively decrease the general psycho-pathological symptoms and increase self-esteem level and psychological flexibility in people with schizophrenia in remission.


Systematic, standardized and comprehensive neurological phenotyping of inbred mice strains in the German Mouse Clinic.
Neurological and psychiatric disorders are among the most common and most serious health problems in developed countries. Transgenic mouse models mimicking human neurological diseases have provided new insights into development and function of the nervous system. One of the prominent goals of the German National Genome Research Network is the understanding of the in vivo function of single genes and the pathophysiological and clinical consequences of respective mutations. The German Mouse Clinic (GMC) offers a high-throughput primary screen of genetically modified mouse models as well as an in-depth analysis in secondary and tertiary screens covering various fields of mouse physiology. Here we describe the phenotyping methods of the Neurological Screen in the GMC, exemplified in the four inbred mouse lines C57BL/6J, C3HeB/FeJ, BALB/cByJ, and 129S2/SvPas. For our primary screen, we generated "standard operating procedures" that were validated between different laboratories. The phenotyping of inbred strains already showed significant differences in various parameters, thus being a prerequisite for the examination of mutant mouse lines.


The type-1 ribosome-inactivating protein OsRIP1 triggers caspase-independent apoptotic-like death in HeLa cells.
Ribosome-inactivating proteins (RIPs) are capable of removing a specific adenine from 28S ribosomal RNA, thus inhibiting protein biosynthesis in an irreversible manner. In this study, recombinant OsRIP1, a type 1 RIP from rice (Oryza sativa L.), was investigated for its anti-proliferative properties. Human cervical cancer HeLa cells were incubated in the presence of OsRIP1 for 24-72 h. OsRIP1 treatment yielded an anti-proliferation response of the HeLa cells and resulted in apoptotic-like blebbing of the plasma membrane without causing DNA fragmentation. OsRIP1 labeled with FITC accumulated at the cell surface. Pull-down assays identified ASPP1 (Apoptosis-Stimulating Protein of p53 1) and IFITM3 (interferon-induced transmembrane protein 3) as potential interaction partners for OsRIP1. Transcript levels for several critical genes related to different signaling pathways were quantified by RT-qPCR. OsRIP1 provoked HeLa cells to undergo caspase-independent cell death, associated with a significant transcriptional upregulation of the apoptotic gene PUMA, interferon regulatory factor 1 (IRF1) and the autophagy-related marker LC3. No changes in caspase activities were observed. Together, these data suggest that apoptotic-like events were involved in OsRIP1-driven caspase-independent cell death that might trigger the IRF1 signaling pathway and LC3-mediated autophagy.


Psychosocial status of patients randomly assigned to medical or surgical therapy for chronic stable angina.
Aspects of social and psychologic functioning are compared for 51 patients randomly assigned to surgical or medical management of chronic stable angina. No differences were found between the two groups in work status, social activity, adequacy of family functioning, perceived health, life satisfaction, memory span, extent of anxiety, hypochondriasis and hysteria. However, surgically treated patients were significantly less depressed and more likely to report improvement in health and family functioning after the initiation of treatment. It is concluded that the psychologic and social outcomes appear slightly more favorable in patients treated surgically than in those treated medically.


Anti-arthritic effect of berberine on adjuvant-induced rheumatoid arthritis in rats.
Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease, which affects approximately 1% adult population in the worldwide. The present study was to investigate the anti-arthritic effect of berberine and its involved mechanism in Freund's complete adjuvant (FCA) induced arthritis rats. Rats were divided randomly into control, FCA, tripterysium glycosides, berberine (75 and 150mg/kg). The apparent indicators, including changes of body weights, paw swelling degrees and arthritis indexes, were analyzed to evaluate anti-arthritic effect of berberine. The levels of IL-6, IL-10, IL-17 and TGF-β in serum were measured by ELISA. Histopathological changes and immunohistochemical expression of anti-IL-10 and anti-IL-17 antibodies in ankle joint tissues were examined. Berberine obviously suppressed the severity of RA rats by attenuating the apparent indicators as mentioned above. Meanwhile, berberine significantly decreased the levels of IL-6 and IL-17, and increased the levels of IL-10 and TGF-β. Histopathological examinations indicated that berberine attenuated the synovial hyperplasia and inflammatory cell infiltration in joint tissues. In addition, immunohistochemical results showed that the amount of anti-IL-10 antibody increased, while the amount of anti-IL-17 antibody decreased in ankle tissues of arthritis rats. Our results showed that berberine exerted a superior anti-arthritic effect and the mechanism maybe involve the balance between Treg and Th17 cells.


[Experimentally induced heart muscle fiber necroses after premedication with strophanthin (author's transl)].
Number and degree of angiotensin-induced heart muscle necrosis in the rat (75 mg/kg body weight) are diminuished by premedication with strophanthin (2 X 10(-2) MG/KG BODY WEIGHT). The electron-microscopic findings are also changed: the application of angiotensin only results in vacuolization of mitochondria and a dilatation of theendoplasmatic reticulum while myofibrils are unaltered. Angiotensin in combination with strophanthin has a direct destructive effect on the myofibrils without evident changes of the mitochondria and tubular system of the heart. The protective action of Strophanithin on the heart muscle cell is discussed in the sense of an exonomization of the cellular metabolism under conditions of relative coronary insufficiency, induced by the vasoconstructive effect of angiotensin.


Histological chorioamnionitis is increased at extremes of gestation in stillbirth: a population-based study.
To determine the incidence of histological chorioamnionitis and a fetal response in stillbirths in New South Wales (NSW), and to examine any relationship of fetal response to spontaneous onset of labour and to unexplained antepartum death. Population-based cohort study. Setting. New South Wales Australia. Population. All births between 2002 and 2004 with stillbirths reviewed and classified by the state perinatal mortality review committee. Record linkage of the Midwives Data Collection and the Perinatal Death Database including placental histopathology and standardised cause of death classification. 952 stillbirths were included. The incidence of histopathological chorioamnionitis was 22.6%, with a bimodal distribution. A fetal inflammatory response was present in 10.1% and significantly correlated with spontaneous onset of labour. The absence of a fetal inflammatory response was strongly associated with unexplained antepartum death. The increased incidence of histological chorioamnionitis at extremes of gestation is confirmed in the largest dataset to date using population data. This has important implications for late gestation stillbirth as the percentage of unexplained stillbirths increases near term.


ResolvinD1 stimulates epithelial wound repair and inhibits TGF-β-induced EMT whilst reducing fibroproliferation and collagen production.
Acute and chronic inflammatory lung diseases are often associated with epithelial cell injury/loss and fibroproliferative responses. ResolvinD1 (RvD1) is biosynthesized during the resolution phase of inflammatory response and exerts potent anti-inflammatory and promotes resolution of inflammatory lung diseases. The aim of this study was to investigate whether RvD1 exerts protective effects on alveolar epithelial cell function/differentiation and protects against fibroproliferative stimuli. Primary human alveolar type II cells were used to model the effects of RvD1 in vitro upon wound repair, proliferation, apoptosis, transdifferentiation, and epithelial-mesenchymal transition (EMT). Effects of RvD1 upon primary human lung fibroblast proliferation, collagen production, and myofibroblast differentiation were also examined. RvD1 promoted alveolar type II (ATII) cell wound repair and proliferation. RvD1 protected ATII cells against sFas-ligand/TNF-α-induced apoptosis and inhibition on cell proliferation and viability. RvD1 promoted ATII cells transdifferentiation. Moreover, we demonstrate that RvD1 inhibited EMT in response to TGF-β. Furthermore RvD1 inhibited human lung fibroblast proliferation, collagen production, and myofibroblast differentiation induced by both TGF-β and bronchoalveolar lavage fluid from acute respiratory distress syndrome (ARDS) patients. The effects of RvD1 were PI3-kinase dependent and mediated via the resolvin receptor. RvD1 seems to promote alveolar epithelial repair by stimulating ATII cells wound repair, proliferation, reducing apoptosis, and inhibiting TGF-β-induced EMT. While RvD1 reduced fibroproliferation, collagen production, and myofibroblast differentiation. Together, these results suggest a potential new therapeutic strategy for preventing and treating chronic diseases (such as idiopathic pulmonary fibrosis) as well as the fibroproliferative phase of ARDS by targeting RvD1 actions that emphasizes natural resolution signaling pathways.


Cytokine profiles affecting the pathogenesis of autoimmune hepatitis in Japanese patients.
Autoimmune hepatitis (AIH) is a chronic hepatitis of unknown etiology, although several cytokines have been implicated in its pathogenesis and severity. This study investigated the relationship between circulating cytokines in the pretreatment phase and remission following corticosteroid therapy phase in Japanese AIH patients. A total of 28 cytokines were measured simultaneously by multiple bead array technology in the sera of 40 patients with AIH collected during pretreatment and remission phases. Interleukin (IL)-12p40, interferon-γ-inducible protein (IP-10), macrophage inflammatory protein (MIP)-1α, MIP-1β, IL-17F and IL-18 were significantly decreased during remission from pretreatment stage levels. The level of IP-10 in the pretreatment phase was correlated with serum levels of alanine aminotransferase. Our results suggest that a complex interplay of several cytokines, especially pro-inflammatory and T-helper 17 cytokines and regulatory T-cell suppression by IL-12p40 may play a pivotal role in the pathogenesis of AIH.


Ventricular venting during coronary revascularization: assessment of benefit by intraoperative ventricular function curves.
Although the physiological benefits of left ventricular venting during cardiopulmonary bypass have been documented experimentally, air embolus is still a concern clinically, and surgeons, therefore, continue to debate whether or not to vent routinely during coronary revascularization. In this study, 10 patients vented during revascularization and 10 not vented were studied immediately before and after cardiopulmonary bypass using Sarnoff ventricular function curves to assess changes in ventricular performance. Stroke work index by each patient before and after bypass was compared at common left atrial pressures and concomitant similar systemic resistances. In patients who were vented, there was overall no change in function (98 +/- 7% of control; range, 146--73%). In patients who were not vented, there was overall significant depression of function (67 +/- 5% of control; range, 91--45%, p less than 0.01). The overall absence of depression in patients who were vented, several of whom had very poor ventricles before bypass, strongly supports venting for coronary revascularization.


Response reversal and children with psychopathic tendencies: success is a function of salience of contingency change.
Previous work has inconsistently reported difficulties with response reversal/extinction in children with psychopathic tendencies. We tested the hypothesis that the degree of impairment seen in children with psychopathic tendencies is a function of the salience of contingency change. We investigated the performance of children with psychopathic tendencies on a novel probabilistic response reversal task involving four conditions with gradated reward-punishment contingencies (100-0, 90-10, 80-20 and 70-30; i.e., for the 100-0 contingency, responding to one object is always rewarded while responding to the other is always punished). In line with predictions, the impairment seen in the children with psychopathic tendencies was an inverse function of the salience of the contingency change. We suggest that this data is consistent with suggestions of subtle orbital frontal cortex impairment in children with psychopathic tendencies.


Provoked versus unprovoked venous thromboembolism: Findings from GARFIELD-VTE.
Venous thromboembolism (VTE) has a long-term risk of recurrence, dependent on the presence or absence of provoking risk factors at the time of the event. To compare clinical characteristics, anticoagulant patterns, and 12-month outcomes in patients with transient provoking factors, active cancer, and unprovoked VTE. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE is a prospective, observational study that enrolled 10 207 patients with objectively diagnosed VTE from 415 sites in 28 countries. Patients with transient provoking factors were younger (53.0 years) and more frequently women (61.2%) than patients with unprovoked VTE (60.3 years; 43.0% women) or active cancer (63.6 years; 51.7% women). After 6 months, 59.1% of patients with transient provoking factors remained on anticoagulation, compared to 71.3% with unprovoked VTE and 47.3% with active cancer. At 12 months, this decreased to 36.7%, 51.5%, and 25.4%, respectively. The risk of mortality (hazard ratio [HR], 1.21; 95% confidence interval [CI], 0.90-1.62), recurrent VTE (HR, 0.84; 95% CI, 0.62-1.14), and major bleeding (HR, 1.26; 95% CI, 0.86-1.85) was comparable in patients with transient provoking factors and unprovoked VTE. Patients with minor and major transient provoking factors had a similar risk of recurrent VTE (HR, 0.99; 95% CI, 0.59-1.66), but those with major transient risk factors had a lower risk of death (HR, 0.61; 95% CI, 0.38-0.98). At 1 year, nearly 40% of patients with transient provoking factors and slightly over half of patients with unprovoked VTE were on anticoagulant treatment. Event rates were comparable between the two groups. Risk of death was higher in patients with minor transient factors than in those with major transient factors.


Tool acceptance and acceptability: insights from a real tool use activity.
The issue of tool adoption has been the subject of many investigations, which focus either on acceptability (evaluating intention to use, a priori) or acceptance (evaluating real tool use, a posteriori). There are many criteria in the literature explaining why a tool is accepted or rejected by users, but behavioral observations are rare. This work aims to study the relationship between acceptability and acceptance and to find out if there is a hierarchy between the criteria that lead a user to use a particular tool. We exposed participants to eight xylophones varying according to three criteria: Ease of use, Utility, and Aesthetics. We assessed acceptability and judgment of participants about xylophones with questionnaires, based on tool use observation in a video session, and after a short-term use (Experiment 1); we also measured acceptance after long-term use of five sessions during which participants learned to play xylophone (Experiment 2). The results suggested that previous exposure to the tool influenced the judgment of the user, indicating a difference between acceptability and acceptance and between observation and use of a tool. The results also indicate differences in the hierarchy of criteria. In the acceptability phase, user judgments are guided by Ease of use. However, during the acceptance phase, the Utility criterion has the greatest influence, whether in terms of tool preference, or time spent using tools.


Inappropriate thyroid-stimulating hormone release in the elderly?
In three hyperthyroid women aged more than 60 years serum TSH levels, inhibited as usual before treatment, rose and remained elevated for more than one year while on treatment with methimazole and l-thyroxine, in spite of serum T3 and T4 levels within the normal range. In two hypothyroid women aged more than 60 years, serum TSH levels, raised under basal conditions, failed to be suppressed by a one-year treatment with l-thyroxine. Repeated attempts to increase serum T3 and T4 concentrations by giving additional doses of l-thyroxine or by tapering methimazole dosage, led to clinical signs of hyperthyroidism, not accompanied by a significant reduction of serum TSH levels. These data indicate the possibility of an inappropriate TSH release in some elderly people.


A seven-day volumetric spore trap for use within buildings.
The Burkard Volumetric spore trap, designed to operate for seven days continuously in the field, was modified to sample still air within buildings. The efficiency with which spores of Lycopodium clavatum and Agaricus bisporus were trapped at two rates of suction was determined. Spore distribution within traces and deposition on surfaces not beneath the orifice were assessed. In an appendix catches of four spore types by the Hirst and Burkard (field model) spore traps operating over mown grass were compared.


The SPIKES protocol does not influence the tolerance or effectiveness of intra-articular corticosteroid injection in the knees of osteoarthritis patients: A prospective, controlled, randomized single-blinded trial.
Patient user embracement involves behaviours of including and listening to the patient, appreciating their complaints, and identifying their needs, whether individual or collective. The aim of this study was to evaluate the influence of a user embracement protocol (SPIKES protocol) for patients with knee osteoarthritis (OA) immediately before intra-articular injection (IAI) relative to procedure tolerance and its effectiveness in the immediate, short and medium terms. This was a randomized controlled trial. Patients received IAIs with triamcinolone hexacetonide (40 mg) preceded or not by the SPIKES protocol. The outcomes measured were: visual analogue scale for pain at rest, pain on movement and joint swelling; morning stiffness; Western Ontario McMaster Universities Index Functional Questionnaire (WOMAC); pain catastrophizing scale; McGill pain questionnaire; SF-36 questionnaire on quality of life; Trace State Anxiety Inventory (IDATE); and a Timed Up and Go functional test. One hundred patients were randomized in the user embracement group (n = 50) or the control group (n = 50); 89% were women and 60% white, mean age was 67.1 (±7.3) years, and mean disease time was 6.3 (±6.2) years. No statistically significant differences were found between the groups for any variables at pre-procedure time, nor did the groups differ in their tolerance to the procedure or during the 12 weeks of follow up for any evaluated variables. No benefit was identified by applying a user embracement protocol to patients with knee OA prior to IAI with corticosteroid, neither to tolerance at the time of the procedure nor to its effectiveness in the immediate, short, and medium terms.


Implementation of a comprehensive fertility biobanking initiative.
To present the framework of Stanford Fertility and Reproductive Health's comprehensive reproductive biobanking initiatives and the results of the first year of recruitment. Technical description article. Academic fertility center. Fertility patients >18 years of age. Enroll the patients interested in research in biobanking protocols. Patient recruitment and sample inventory from September 2020 to September 2021. A total of 253 patients have enrolled in the Stanford Fertility and Reproductive Health biobanking initiatives since September 2020. The current inventory consists of 1,176 samples, including serums, plasmas, buffy coats, endometria, maternal deciduae, miscarriage chorionic villi, and human embryos (zygote, cleavage, and blastocyst stages). This biobanking initiative addresses a critical, unmet need in reproductive health research to make it possible for patients to donate excess embryos and gametes and preserves, for future research, valuable somatic and reproductive tissues that would otherwise be discarded. We present the framework of this biobanking initiative in order to support future efforts of establishing similar biorepositories.


Pilot study: evaluation of the effect of functional electrical stimulation cycling on muscle metabolism in nonambulatory people with multiple sclerosis.
To investigate the changes in muscle oxygen consumption (mV˙O2) using near-infrared spectroscopy (NIRS) after 4 weeks of training with functional electrical stimulation (FES) cycling in nonambulatory people with multiple sclerosis (MS). Four-week before-after trial to assess changes in mV˙O2 after an FES cycling intervention. Rehabilitation hospital. People (N=8; 7 men, 1 women) from a volunteer/referred sample with moderate to severe MS (Expanded Disability Status Scale score>6.0). Participants cycled 30 minutes per session, 3d/wk for 4 weeks or a total of 12 sessions. mV˙O2 of the right vastus lateralis muscle was measured with NIRS before and within 1 week after the intervention. Six bouts of 15-second electrical stimulation increasing from 2 to 7Hz were used to activate the muscle. mV˙O2 was assessed by analyzing the slope of the NIRS oxygen signal during a 10-second arterial occlusion after each electrical stimulation bout. Significant FES training by electrical stimulation frequency level interaction was observed (P=.031), with an average increase in mV˙O2 of 47% across frequencies with a main effect of training (P=.047). FES cycling for 4 weeks improved mV˙O2, suggesting that FES cycling is a potential therapy for improving muscle health in people with MS who are nonambulatory.


Identification of drug-related problems followed by clinical pharmacist interventions in an outpatient pharmacotherapy clinic.
Pharmacotherapy is an essential strategy for the treatment of many medical conditions especially chronic disease and often involves multiple medications being used simultaneously. Increasing the use of medications may pose some challenges to safe and effective drug therapy and if not identified and prevented by the pharmacists eventually can lead to drug-related problems (DRPs). The present study aimed to examine the incidence of DRPs in Iranian patients and to evaluate patients' adherence to the clinical pharmacist interventions as well as the physicians' acceptance of these recommendations. This study was conducted in a university-affiliated outpatient pharmacotherapy clinic over a 22-month period. Patients aged 18 years and older with at least one chronic disease receiving at least four medications were included in the study. The patients were interviewed by a clinical pharmacist for comprehensive medication review. DRPs were identified using the DOCUMENT classification system. Recommendations were provided by the clinical pharmacist including interventions involving patient and/or physician to resolve DRPs. The patients were followed up after 2 weeks to evaluate their compliance and physician acceptance of clinical pharmacist recommendations. Two hundred patients were included in this study. Overall, 875 DRPs were identified with an average of 4.37 per patient. The most prevalent DRPs were related to patient education or information (22.8%), undertreated indications (17.4%) and patient compliance (17.2%). The most common drugs associated with DRPs were alimentary and metabolism (22.2% of DRPs) followed by the cardiovascular system (19.2%) and nervous system (9.6%) medications. The DRP incidence correlated with gender only and was higher in females (p = 0.019). The clinical pharmacist provided 912 interventions with an average of 4.56 and 1.04 interventions per patient and per DRPs respectively. Patient education (41.3%), medication initiation or discontinuation (24.5%), and non-pharmacological interventions (12.9%) were the most common clinical pharmacist interventions. Out of 912 interventions, 665 were followed up, out of which 427 were patient dependent and 228 involved physicians. The patient's compliance with clinical pharmacist recommendations was 81.2%. The physician acceptance rate of the recommendations was 44.1%. The study shows that especially designed services such as pharmacotherapy clinics running by clinical pharmacists are necessary to detect and resolve DRPs in an effective way. The high compliance rate of the patients indicates patients' confidence in the clinical pharmacist services provided in the pharmacotherapy clinic. The low acceptance rate of the physicians highlights the need to improve interprofessional collaboration between clinical pharmacists and physicians in an outpatient setting.


Synthesis, in vivo and in silico analgesic and anti-inflammatory studies of α-D-ribofuranose derivatives.
Five α-D-ribofuranose analogues (2, 3, 4, 5 and 6) were synthesized in good yields from 3-O-benzyl-4-C-(hydroxymethyl)-1, 2-O-isopropylidene-α-D-ribofuranose (1). The synthesized compounds were then subjected to analgesic, anti-inflammatory, antimicrobial and antioxidant assays. Compound 3 demonstrated 79.74% (P < 0.001) writhing inhibition and highest reaction time of 2.55 ± 0.13 min (P < 0.001) after 30 min of oral administration in peripheral and central analgesic assay, respectively, at 50 mg/kg dose. Compound 2 and 6 exhibited significant anti-inflammatory activity at 100 mg/kg dose with paw edema inhibition of 91.15% (P < 0.001) and 95.13% (P < 0.001), respectively, in 4th hour. The synthesized analogues did not show notable antioxidant and antibacterial properties. Molecular docking study revealed higher binding affinity of -8.1 kcal/mol and -8.9 kcal/mol of compound 3 towards cyclooxygenase-1 and phospholipase A2, respectively, compared to -7.7 and -7.6 kcal/mol respectively for corresponding native ligands. Compound 2 demonstrated binding affinity of -9.1 kcal/mol towards interleukin-1 receptor-associated kinase-4 compared to -8.7 kcal/mol of the native ligand. The molecular properties related to drug likeness of compounds were found to be within acceptable range. Synthesized D-ribofuranose analogues demonstrated promising analgesic and anti-inflammatory activities and further development may lead to new potent analgesic and anti-inflammatory agents.


Using learning flexibly and remembering after a delay: understanding cognitive dysfunction in adults with Down syndrome.
Episodic memory deficits are a characteristic of cognitive dysfunction in people with Down syndrome (DS). However, less is known about the processes (i.e. encoding, retention or using learned information flexibly) that underlie these deficits. We explored these abilities by administering a relational memory and inference task to participants with DS and mental age-matched controls and testing both immediately and after a 24-h delay. Adults with DS learned paired associates more slowly than controls but showed good recognition at both the immediate and delayed tests. Despite memory for learned pairs, adults with DS were less able to use relational learning flexibly to make inferential judgements than controls. These results deepen our understanding of the cognitive profile of adults with DS, demonstrating deficits in both encoding new information, and flexibly using such information. These results have important implications for workplace training and intervention programs for people with DS.


The formation of nanoscale structures in soluble phosphosilicate glasses for biomedical applications: MD simulations.
The occurrence of chain-like fragments and rings in phosphosilicate glasses of known bioactivity was examined using classical molecular dynamics simulations, in order to reveal the possible effect of such nanostructures on the bioactive behaviour. Highly bioactive compositions display a large fraction of non-crosslinked, nonlinear chains of tetrahedra, which are not present in bio-inactive compositions. The low(er) energetic cost associated with the direct release of these silicate fragments into solution can assist the fast partial dissolution observed for bioactive glass compositions. Loss of bioactivity when the silicate content increases is accompanied by the transformation of these chains into small closed rings (3- to 8-membered), which appear to protect the silicate network from fast dissolution.


[Functional reeducation of the perineum by the intermittent static contraction method].
In this original method of improving muscle tone in the perineum the author adapts the technique used for strengthening the quadriceps muscles. In that method the muscles progressively pull against an increasing weight. This method adapted to the perineum can be performed if a tampon is inserted into the vagina and the patient is instructed to contract her muscles so that increasingly heavy weights attached to the thread by which the tampon is normally removed are applied and the patient is taught how to contract so that the tampon is held in place. Furthermore the patient is taught breathing exercises together with abdomino-perineal muscle development, using H. Stapfer's method which was first described in his book published in 1912. Two case histories illustrate how the method has been applied and there are also diagrams showing how to carry out the exercises and how not to carry them out.


Paying to waste lives: the affordability of reducing mother-to-child transmission of HIV in South Africa.
It is estimated that each HIV-positive child in South Africa costs the government more in terms of health and welfare expenses than it does to reduce mother-to-child transmission (MTCT) of HIV through the use of antiretroviral regimens (where the mother continues to breast-feed). Programmes to reduce MTCT of HIV/AIDS are, thus, clearly affordable. Using Nevirapine (according to the HIVNET 012 Protocol) saves more lives and [corrected] is more cost-effective than using Zidovudine (CDC 2 weeks regime).


The exosome: a review of current therapeutic roles and capabilities in human reproduction.
Exosomes are nano-vesicles (30-150 nm) which may be useful as therapeutic delivery vehicles and as diagnostic biomarkers. Exosomes are produced naturally within the human body and therefore are not prone to immunogenicity effects which would otherwise destroy unelicited foreign bodies. Clinically, they have been regarded as ideal candidates for applications relating to biomarker developments for the early detection of different diseases. Furthermore, exosomes may be of interest as potential drug delivery vehicles, which may improve factors such as bioavailability of loaded molecular cargo, side effect profiles, off-target effects, and pharmacokinetics of drug molecules. In this review, the therapeutic potential of exosomes and their use as clinical biomarkers for early diagnostics will be explored, alongside exosomes as therapeutic delivery vehicles. This review will evaluate techniques for cargo loading, and the capacity of loaded exosomes to improve various reproductive disease states. It becomes important, therefore, to consider factors such as loading efficiency, loading methods, cell viability, exosomal sources, exosome isolation, and the potential therapeutic benefits of exosomes. Issues related to targeted drug delivery will also be discussed. Finally, the variety of therapeutic cargo and the application of appropriate loading methods is explored, in the context of establishing clinical utility. Exosomes have more recently been widely accpeted as potential tools for disease diagnostics and the targeted delivery of certain therapeutic molecules-and in due time exosomes will be utilised more commonly within the clinical setting. Specifically, exosomal biomarkers can be identified and related to various detrimental conditions which occur during pregnancy. Considering, this review will explore the potential future of exosomes as both diagnostic tools and therapeutic delivery vehicles to treat related conditions, including the challenges which exist towards incorporating exosomes within the clinical environment to benefit patients.


Senescent cells in human adipose tissue: A cross-sectional study.
Adipose tissue (AT) senescence is associated with AT dysfunction in rodents, but little is known about human AT senescence. The study goal was to define the distribution of senescent cells in two subcutaneous depots and understand relationships with adiposity and inflammation. Sixty-three volunteers (48 females) underwent abdominal and femoral subcutaneous fat biopsies. Fat cell size, senescent cells using senescence-associated β-galactosidase staining per 100 nucleated cells (percentage), and mRNA expression of four cytokines were measured. There was a larger proportion of senescent cells in femoral than abdominal subcutaneous AT (mean difference 1.6% [95% CI: 0.98%-2.3%], p < 0.001), and the percentage of femoral AT senescent cells was greater in women than men (median 3.9% vs. 2.1%, p < 0.01). There was a positive correlation between senescence and fat cell size in abdominal (rs = 0.44, p < 0.001) and femoral (rs = 0.35, p = 0.007) AT depots. Abdominal AT tumor necrosis factor alpha (rs = 0.49, p < 0.01) and interleukin-1β (rs = 0.44, p = 0.01) expression was positively correlated with abdominal, but not femoral, AT senescence. In human subcutaneous AT, there are more senescent cells in femoral than abdominal depots; abdominal AT senescent cells are more associated with inflammatory signals than femoral AT senescent cells.


The acuityscope: a resolution test target projection ophthalmoscope.
The Acuityscope projects an image of a three bar resolution test target onto the patient's retina, where it is viewed and read by an observer. The test target consists of a series of three bar targets varying in size on a logarithmic scale. Individual targets are identified in the projected image by Bailey-Lovie log visual acuity equivalents. The projected image includes only those target sizes which are useful for estimating visual acuity. The Acuityscope is used for assessing the quality of retinal image formation, and is thus able to differentiate between poor visual acuity due to image degradation, (e.g. cataract or corneal disease) and poor visual acuity due to image handling defects (e.g. retinal or optic nerve disease). The use of the instrument is relevant to both clinical situations (e.g. pre-operative assessment of opacification of optical media) and experimental situations (e.g. clinical trials).


New approach for the quantification of metallic species in healthcare products based on optical switching of a Schiff base possessing ONO donor set.
A new method is reported for the quantification of some metallic components of healthcare products utilizing a Schiff base chelator derived from 2-hydroxyacetophenone and ethanolamine. The Schiff base chelator recognizes some metallic species such as iron, copper and zinc (important components of some healthcare products), and cadmium (common contaminant in healthcare products) giving colorimetric/fluorimetric response. It coordinates with Fe2+/Fe3+ and Cu2+ ions via ONO donor set and switches the colour to bright red, green and orange, respectively. Similarly, it switches 'ON' a fluorometric response when coordinates with Zn2+ and Cd2+ ions. In the present approach, detailed studies on the colorimetric and fluorimetric response of ONO Schiff base is investigated in detail. The Job plot for the complexation of ONO switch with various metal ions suggested formation of 1:1 (metal-chelator) complex with Fe2+, Fe3+, and Cu2+ while 1:2 (metal-chelator) for Zn2+ and Cd2+ ions. The limit of detection, limit of quantification are 6.73, 18.0, 25.0, 0.65, 1.10μM and 27.0, 72.0, 100.0, 2.60 and 4.40μM for Fe2+, Fe3+, Cu2+, Zn2+ and Cd2+ ions, respectively. Under the optimized conditions, chelator was used for the quantification of important metals present in healthcare products via direct dissolution and furnace treatment during sample preparation. The results were found precise and accurate for both sample preparation techniques using the developed method.


Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine β-synthase.
Acute pancreatitis is an inflammatory process of the pancreatic gland that may lead to dysregulation of the trans-sulfuration pathway. The aims of this work were firstly to study the methionine cycle as well as the trans-sulfuration pathway using metabolomic and proteomic approaches identifying the causes of this dysregulation in an experimental model of acute pancreatitis; and secondly to reveal the effects of S-adenosylmethionine administration on these pathways. Acute pancreatitis was induced by cerulein in mice, and a group of animals received S-adenosylmethionine treatment. Cerulein-induced acute pancreatitis rapidly caused marked depletion of methionine, S-adenosylmethionine, 5'-methylthioadenosine, cystathionine, cysteine, and glutathione levels in pancreas, but S-adenosylhomocysteine and homocysteine remained unchanged. Protein steady-state levels of S-adenosylhomocysteine-hydrolase and cystathionine gamma-lyase diminished but methylthioadenosine phosphorylase levels increased in pancreas with acute pancreatitis. Although cystathionine β-synthase protein levels did not change with acute pancreatitis, Nos2 mRNA and protein levels were markedly up-regulated and caused tyrosine nitration of cystathionine β-synthase in pancreas. S-adenosylmethionine administration enhanced Nos2 mRNA expression and cystathionine β-synthase nitration and triggered homocysteine accumulation in acute pancreatitis. Furthermore, S-adenosylmethionine administration promoted enrichment of the euchromatin marker H3K4me3 in the promoters of Tnf-α, Il-6, and Nos2 and enhanced the mRNA up-regulation of these genes. Accordingly, S-adenosylmethionine administration increased inflammatory infiltrate and edema in pancreas with acute pancreatitis. In conclusion, tyrosine-nitration of cystathionine β-synthase blockades the trans-sulfuration pathway in acute pancreatitis promoting homocysteine accumulation upon S-adenosylmethionine treatment.


Myocardial injury is a risk factor for 6-week mortality in liver cirrhosis associated esophagogastric variceal bleeding.
This study sought to investigate risk factors for 6-week mortality of patients with decompensated liver cirrhosis associated esophagogastric variceal bleeding (EGVB) and clinical characteristics of myocardial injury in cirrhotic patients with EGVB. This retrospective cohort study included 249 patients with decompensated liver cirrhosis associated EGVB in the Department of Emergency. Patients were divided into two groups including liver cirrhosis associated EGVB without myocardial injury and liver cirrhosis associated EGVB with myocardial injury. Myocardial injury, recurrent bleeding, total bilirubin (TBIL) level and dyslipidemia are independent risk factors for 6-week mortality in liver cirrhosis associated EGVB. Among all patients with liver cirrhosis associated EGVB, 90 (36.2%) had myocardial injury and 159 individuals (63.8%) not. The 6-week mortality in the group with myocardial injury was 21%, which was significantly higher than that of 7% in the group without myocardial injury. More patients in the myocardial injury group smoked, had moderate to severe esophageal varices, liver failure, and Child-Pugh C liver function compared to the non-myocardial injury group. Myocardial injury, recurrent bleeding, TBIL level and dyslipidemia are independent risk factors for death within 6 weeks in liver cirrhosis associated EGVB. The 6-week mortality is considerably higher in patients with myocardial injury in liver cirrhosis associated EGVB than those without myocardial injury.


Topical treatment of tea saponin stabilized silybin nanocrystal gel reduced oxidative stress in UV-induced skin damage.
UV-induced peroxidation is a significant factor in skin damage. Some natural products have been utilized to protect the skin. However, most of them suffer from issues such as poor bioavailability. A promising strategy is to prepare them as safe and convenient gels. In this study, we constructed Silybin Nanocrystal Gel (SIL-NG). Tea saponin, a spatial stabilizer that we have previously reported, was used to prepare SIL-NS and subsequently combined with xanthan gum to prepare SIL-NG with an excellent safety profile. This nanogel with a natural stabilizer has a suitable ductility and shows a good safety profile in vitro and in vivo. In L929 cells, SIL-NG was able to reduce H2O2-induced ROS levels. In addition, SIL-NG exhibited better antioxidant activity compared to SIL-NS. SIL-NG was able to reduce UVB irradiation-induced oxidative damage in mice, significantly increase SOD activity, and reduce MDA levels. In conclusion, our work gives a new perspective on the treatment of UV skin damage using natural ingredients.


Probing protein aggregation by time-resolved fluorescence during beta-lactoglobulin crystal growth.
We have used the fluorescence anisotropy (FA) decay of retinol bound to bovine beta-lactoglobulin to monitor the time evolution of protein aggregation during the early stages of crystal growth. With this approach we have followed the formation of aggregates at different concentrations of ammonium sulfate, the precipitant used for crystallization. The average aggregation number is found to depend on precipitant concentration, and to be restricted to small numbers ranging from 2 to 5, also in the presence of visible growing crystals. The effect of particle distribution and of low probe-to-protein saturation on the FA response is also discussed in detail.


Cross-reactivity between natural rubber latex and food allergens.
Immediate-type hypersensitivity to latex is a growing problem, especially among health care workers (HCWs) and patients requiring long-term catheterization and multiple operations. The responsible allergens are latex proteins, which are found in raw latex, as well as in various latex-containing products. More than 200 polypeptides can be discerned in latex sap and of these, 60 proteins showed reactivity with IgE antibodies from patients with latex allergy. Several of these proteins have been characterized at the molecular level and their role in latex allergy has been elucidated. Latex allergy is often associated with hypersensitivity to certain fruits and vegetables like avocado, kiwi, banana, sweet pepper, and tomato. Several case reports demonstrate a potential for serious allergic reactions to foods in latex allergic patients. Nevertheless, comprehensive studies on the clinical significance and relevance of this co-sensitization are missing. Although some of the latex allergens are ubiquitous plant proteins or share structural features with plant proteins, the molecular bases of these cross-reactivities have not yet been clarified.


[Nature of the relation between contractile activity indices of the left and right heart ventricles in normal and pathological conditions].
Positive correlations were established between contractile activity of left and right rabbit ventricles in normal conditions, reflecting synchronous activity of both heart ventricles. These correlations could be broken in case of pathology due to disturbances of adaptation mechanisms resulting in the impairment of heart functioning.


Should we be talking about guidelines with patients? A qualitative analysis in metastatic breast cancer.
Little data exist on perceptions of guideline-based care in oncology. This qualitative analysis describes patients' and oncologists' views on the value of guideline-based care as well as discussing guidelines when making metastatic breast cancer (MBC) treatment decisions. In-person interviews completed with MBC patients and community oncologists and focus groups with academic oncologists were audio-recorded and transcribed. Two coders utilized a content analysis approach to analyze transcripts independently using NVivo. Major themes and exemplary quotes were extracted. Participants included 20 MBC patients, 6 community oncologists, and 5 academic oncologists. Most patients were unfamiliar with the term "guidelines." All patients desired to know if they were receiving guideline-discordant treatment but were often willing to accept this treatment. Five themes emerged explaining this including trusting the oncologist, relying on the oncologist's experiences, being informed of rationale for deviation, personalized treatment, and openness to novel therapies. Physician discussions regarding the importance of guidelines revealed three themes: consistency with scientific evidence, insurance coverage, and limiting unusual practices. Oncologists identified three major limitations in using guidelines: lack of consensus, inability to "think outside the box" to personalize treatment, and lack of guideline timeliness. Although some oncologists discussed guidelines, it was often not considered a priority. Patients expressed a desire to know whether they were receiving guideline-based care but were amenable to guideline-discordant treatment if the rationale was made clear. Providers' preference to limit discussions of guidelines is discordant with patients' desire for this information and may limit shared decision-making.


Transformation of amorphous calcium phosphate to bone-like apatite.
Mineralisation of calcium phosphates in bone has been proposed to proceed via an initial amorphous precursor phase which transforms into nanocrystalline, carbonated hydroxyapatite. While calcium phosphates have been under intense investigation, the exact steps during the crystallisation of spherical amorphous particles to platelet-like bone apatite are unclear. Herein, we demonstrate a detailed transformation mechanism of amorphous calcium phosphate spherical particles to apatite platelet-like crystals, within the confined nanodomains of a bone-inspired nanocomposite. The transformation is initiated under the presence of humidity, where nanocrystalline areas are formed and crystallisation advances via migration of nanometre sized clusters by forming steps at the growth front. We propose that such transformation is a possible crystallisation mechanism and is characteristic of calcium phosphates from a thermodynamic perspective and might be unrelated to the environment. Our observations provide insight into a crucial but unclear stage in bone mineralisation, the origins of the nanostructured, platelet-like bone apatite crystals.


Whiteflies (Bemisia tabaci) issued from eggs bombarded with infectious DNA clones of Tomato yellow leaf curl virus from Israel (TYLCV) are able to infect tomato plants.
We have reported previously that Tomato yellow leaf curl virus from Israel (TYLCV) penetrates the reproductive system of its vector, the whitefly Bemisia tabaci biotype B, and may be transmitted to progeny. In order to mimic this phenomenon and to understand how TYLCV accompanies the development of the insect, we have bombarded B. tabaci eggs with an infectious DNA clone of TYLCV. After a linear full-length genomic copy of TYLCV DNA was delivered to eggs, the DpnI-sensitive DNA became circular and DpnI resistant. When a dimeric copy of TYLCV DNA was delivered to eggs, the viral DNA was detected in all the whitefly developmental stages. Adult insects that developed from the treated eggs were able to infect tomato test plants with variable frequency. Viral DNA was detected in the progeny of whiteflies that developed from eggs bombarded with TYLCV. Similarly, when insect eggs were bombarded with a dimeric copy of an infectious clone of the genome of Tomato yellow leaf curl virus from Sardinia, Italy (TYLCSV), adults that eclosed from the treated eggs were able to infect tomato test plants.


Transaxillary minithoracotomy: the optimal approach for certain pulmonary and mediastinal lesions.
This report concerns the use of transaxillary thoracotomy for a variety of pulmonary, pleural, and mediastinal conditions in 50 patients. Primary and metastatic carcinomas, pneumothoraces, and benign lesions such as bronchogenic cysts and neurogenic tumors can be identified, evaluated, and treated with confidence. Reduced postoperative pain and morbidity, rapid return of arm and shoulder movements, reduced hospital stay, and excellent cosmetic result are among the advantages of this approach when compared with the usual posterolateral thoracotomy.


Targeting white matter neuroprotection as a relapse prevention strategy for treatment of cocaine use disorder: Design of a mechanism-focused randomized clinical trial.
Cocaine use continues to be a significant public health problem with limited treatment options and no approved pharmacotherapies. Cognitive-behavioral therapy (CBT) remains the mainstay treatment for preventing relapse, however, people with chronic cocaine use display cognitive impairments that are associated with poor response to CBT. Emerging evidence in animal and human studies suggests that the peroxisome proliferator-activated receptor-gamma (PPAR- γ) agonist, pioglitazone, improves white matter integrity that is essential for cognitive function. This project will determine whether adjunctive use of pioglitazone enhances the effect of CBT in preventing relapse during the early phase of recovery from cocaine use disorder. This paper describes the design of a mechanism-focused phase 2 randomized clinical trial that aims first to evaluate the effects of pioglitazone on targeted mechanisms related to white matter integrity, cognitive function, and cocaine craving; and second, to evaluate the extent to which improvements on target mechanisms predict CBT response. Positive results will support pioglitazone as a potential cognitive enhancing agent to advance to later stage medication development research.