Homocysteine and ischaemic heart disease in the Caerphilly cohort.
Elevated circulating total homocyst(e)ine concentrations are associated with a higher prevalence of ischaemic heart disease (IHD). We utilized data from the Caerphilly Prospective Cohort Study to assess the predictive power of the serum total homocyst(e)ine concentration for future IHD. Serum total homocyst(e)ine concentrations were measured in 2290 men in the Caerphilly cohort, a representative population sample of men aged 50-64 years. During a 5-year follow-up period, 56 men suffered fatal IHD, 77 had a non-fatal myocardial infarction, while 21 were found to have ECG evidence of myocardial infarction (MI) when examined at follow-up. The mean serum total homocyst(e)ine concentration in the total of 154 men who experienced an incident IHD event was 12.4 micromol/l, whereas the 2136 men who experienced no such event had a mean level of 11.7 micromol/l. The difference between these means, examined by logistic regression and standardising for the effects of differences in age, social class, smoking, BMI, diabetes, HDL-cholesterol and prevalent IHD is 0.47 micromol/l (95% CI = -0.13 to 1.11 micromol/l). The mean difference for the 56 men who died, and whose death was attributed to IHD, is 0.81 micromol/l (95% CI= -0.17 to 1.88 micromol/l) after correction for confounding factors. Vitamin nutritional status and alcohol intake were significant negative determinants of serum total homocyst(e)ine concentrations; the effect of alcohol is explained by the folic acid content of beer, which is the preferred alcoholic beverage in Caerphilly. It is concluded that the serum total homocyst(e)ine concentration is weakly predictive of IHD events, though in the present data adjustments for other factors attenuated the relationship and it became not statistically significant (P > 0.05).


Understanding benefit finding among patients with colorectal cancer: a longitudinal study.
Perceiving positive life changes ("benefit finding") is thought to promote better adjustment after cancer, yet is poorly understood among colorectal cancer (CRC) patients. We characterized benefit finding and examined its relationship to demographic/medical factors, change over time, and association with distress. CRC outpatients (N = 133, 50% metastatic) completed self-report measures (demographic/medical factors, benefit finding, distress) at baseline and 6 months later. Wilcoxon rank-sum (Kruskal-Wallis) tests or Spearman correlations tested associations between benefit finding and demographic/medical factors. Linear regressions assessed (1) change in benefit finding over time and whether this differed by demographic/medical factors, and (2) association between benefit finding and distress and whether this changed over time. Benefit finding was common among patients with CRC, with highest rated items reflecting gratitude, acceptance, and stronger family relationships. Women and racial minorities reported greater benefit finding than men (p < 0.001) and White patients (p = 0.015), respectively. Medical factors (e.g., metastatic disease) were not associated with benefit finding. Benefit finding significantly increased over time (p = 0.03). While greater benefit finding trended towards an association with lower distress, results were not statistically significant and the relationship did not change over time. Benefit finding was characterized largely by perceived psychological and social benefits, as opposed to pragmatic benefits. Individual differences and social determinants may be more informative than medical characteristics when it comes to benefit finding; although, cultural factors and mediators should be examined further. Benefit finding seems to evolve over time perhaps as a coping process; however, its association with psychological distress appears tenuous.


Arylsulfatase of human tissue. Studies on a form of arylsulfatase B found predominantly in brain.
The distribution of soluble arylsulfatase (aryl-sulfate sulfohydrolases, EC 184.108.40.206) in human tissues was investigated by DEAE-cellulose chromatography, All tissues examined contained arylsulfatase A and arylsulfatase B. In addition, brain singularly contained significant quantities (15-25% of total arylsulfatase) of a minor anionic arylsulfatase from designated arylsulfatase Bm, whereas only trace amounts of arylsulfatase Bm were found in liver, kidney, testis and placenta. Arylsulfatase B and arylsulfatase Bm had equal activity toward methyl-umbelliferyl sulfate, nitrocatechol sulfate and a physiological substrate UDP-N-acetylgalactosamine 4-sulfate, but both forms were inactive toward the arylsulfatase A substrates cerebroside sulfate and ascorbic acid 2-sulfate. Purified preparations of placental arylsulfatase B, brain arylsulfatase Bm, and urinary arylsulfatase A did not hydrolyze estrone sulfate, dehydroepiandrosterone sulfate or pregnenolone sulfate. The physico-chemical properties of arylsulfatase Band arylsulfatase Bm differed with respect to thermal lability, DEAE-cellulose chromatography, polyacrylamide gel electrophoresis and isoelectric focussing. In the latter technique, utilizing thin polyacrylamide slab gels, the isoelectric point for placental arylsulfatase B was 8.2, while brain arylsulfatase Bm resolved into 3 activity bands with pI values 6.8, 7.0 and 7.2. Although the physico-chemical properties differed, arylsulfatase B and arylsulfatase Bm appear to be functionally equivalent as well as generically related.


TL1A-induced NF-kappaB activation and c-IAP2 production prevent DR3-mediated apoptosis in TF-1 cells.
We recently identified TL1A, an endothelium-derived T cell costimulator and a ligand for tumor necrosis factor receptor superfamily members DR3 and decoy receptor 3. To elucidate the signaling events triggered by TL1A-DR3 interaction and to understand the molecular mechanisms regulating DR3-mediated apoptosis, we have studied the effect of TL1A and an agonistic DR3 monoclonal antibody in human erythroleukemic TF-1 cells, which express DR3 endogenously. TL1A induced the formation of a DR3 signaling complex containing TRADD, TRAF2, and RIP and activated the NF-kappaB and the ERK, JNK, and p38 mitogen-activated protein kinase pathways. However, TL1A or an agonistic DR3 monoclonal antibody did not induce apoptosis in these cells nor were there detectable levels of FADD or procaspase-8 seen in the signaling complex. Interestingly, DR3-mediated apoptosis was induced in TF-1 cells in the presence of a NF-kappaB pathway-specific inhibitor but not in the presence of mitogen-activated protein kinase inhibitors, either alone or in combination, suggesting that DR3-induced NF-kappaB activation was responsible for resistance to apoptosis in these cells. Consistent with this, we found that TL1A significantly increased the production of c-IAP2, a known NF-kappaB-dependent anti-apoptotic protein, and that the NF-kappaB inhibitor or cycloheximide prevented its synthesis. Furthermore, inhibition of c-IAP2 production by RNA interference significantly sensitized TF-1 cells to TL1A-induced apoptosis. Our study identifies a molecular mechanism by which TL1A and DR3 regulate cell fate in TF-1 cells.


Mid-term outcomes of mechanical pulmonary valve replacement: a single-institutional experience of 396 patients.
Previous small-sized studies have demonstrated the safety and efficacy of mechanical pulmonary valve replacement (mPVR) in patients with congenital heart disease; however, the predictors of major complications and reoperation remained unclear. In a retrospective study, we reported the mid-term outcomes of a large-scaled series of patients, 396 patients, with congenital heart diseases who underwent mPVR in a single institution. The patients' mean age at mPVR was 24.3 ± 9 years (4-58 years). Most patients (84.3%) underwent tetralogy of Fallot total correction. The median of follow-up was 36 months (24-49 months). Prosthetic valve malfunction caused by thrombosis or pannus formation developed in 12.1% of patients during follow-up period. Reoperation was performed in 7 cases with pannus formation and 6 cases with mechanical valve thrombosis. Freedom from reoperation at 1, 5, and 10 years was 99%, 97%, and 96%, respectively. Neither early nor mid-term mortalities were detected. Cox regression models showed that male gender and smaller valve size increased the risk of prosthetic valve failure. The age at mPVR, interval between congenital heart defect repair and mPVR, and concomitant procedures predicted reoperation. In multivariate analysis, younger age and the interval between first operation and mPVR predicted reoperation either. The success rate of mPVR is excellent in mid-term follow-up. Younger age, longer interval between the repair of congenital defect and mPVR, and cooperation increased reoperation risk. However, strict adherence to life-long anticoagulation regimen and patient selection are of great importance for the implementation of mPVR.


Enzymatic monitoring of lignin and lignin derivatives biooxidation.
Lignin oxidation was enzymatically monitored by measuring methanol released during the reaction. The methanol was oxidized to formaldehyde and hydrogen peroxide, and the latter used to oxidize ABTS to a product measured spectrophotometrically. The efficiency was comparable to the commonly used gas chromatography method. The assay was fast and inexpensive.


Weight-density relationships in submerged macrophytes : The importance of light and plant geometry.
Crowded stands of submerged plants in Québec lakes have a weight-density with a shallower, but not significantly different, slope and an intercept 10 fold lower than those for terrestial stands. The examination of a larger data set including both freshwater and submerged macrophytes supported these differences. This data set suggested that those differences, as well as those among submerged stands, are largely attributable to the light levels incident upon the stand. The differences in weight-density relationships between submerged and terrestrial stands were paralleled by a smaller biomass per unit volume outgrown of the submerged plants, as predicted from the dimensional examination of the weight-density relationship. The variations in biomass per unit volume associated to differences in the species growth form explained deviations about the weightdensity relationship of stands growing under relatively similar light conditions.


2-Allylphenyl glycosides as glycosyl donors for sugar coupling.
Glycosylations employing 2-allylphenyl glycoside, a new type of stable glycosyl donor, were optimized and explored with a variety of acceptors promoted by ICl/AgOTf. The utility of the protocol was further demonstrated with an efficient synthesis of the disaccharide fragment of bleomycins.


Chronic compartment syndrome in the first dorsal interosseous muscle.
Fifteen patients with clinical signs that could indicate a chronic compartment syndrome of the first dorsal interosseous muscle of the hand were investigated by pressure recording at rest and during exercise. Objective data, verifying such a syndrome, were found in four of the patients. Increased muscle relaxation pressure during exercise and intramuscular pressure at rest after exercise compared with normal pressure were well correlated to the development of the symptoms of chronic compartment syndrome. Fasciotomy of the first dorsal interosseous muscle relieved the symptoms and normalized the pressure.


Physiological localization of the semicircular canal receptors in the crista.
Isolated posterior semicircular canals from the bull frog model were used. The cupula was removed from the crista and the sensory cilia on the crista were depressed toward the canal side by using a glass micropipette. Seven different points were selected for stimulation on the ampullary wall. Ampullary nerve action potentials induced by depression were recorded and were converted into spike-density histograms. Response decremental time constants were measured on these histograms. The longest time constant was measured at the two lateral points of stimulation and progressively shortened toward the central point of stimulation. These results indicate that the origin of the adaptation is possibly sensorineural.


Acceptability of the culturally adapted ASQ-TRAK developmental screening tool to caregivers of Aboriginal children.
The Ages and Stages Questionnaire-Talking about Raising Aboriginal Kids (ASQ-TRAK) culturally adapted developmental screening tool is widely used in Australian Aboriginal communities. However, there has been limited exploration of the tool's acceptability to caregivers. The aim of the study is to determine the acceptability of the ASQ-TRAK developmental screening tool to caregivers of Aboriginal children in urban, regional and remote South Australia. Caregivers of Aboriginal children completed a survey regarding acceptability of the ASQ-TRAK. Convenience samples of caregivers were invited to a telephone interview. Ninety-two caregivers completed the survey (96% response). Acceptability (92%) and caregiver satisfaction (73%) were high. Families perceived the screen as easy to use and understand, strengths-based and providing valuable information about their child's development. The ASQ-TRAK tool was highly acceptable to caregivers in Aboriginal communities in South Australia. The study highlights the importance of culturally safe practice and supports ASQ-TRAK implementation. Broader use and further evaluation of the ASQ-TRAK in Aboriginal communities needs consideration.


Low human papillomavirus (HPV) vaccine uptake among men living with human immunodeficiency virus (HIV): Cross-sectional findings from a clinical cohort.
Men living with human immunodeficiency virus (HIV) are internationally recognized as a priority population for human papillomavirus (HPV) vaccination. Our objective was to explore HPV vaccine uptake among men living with HIV in Ontario, Canada, and investigate differences between vaccinated and unvaccinated men. We used data from a cross-sectional questionnaire administered between 2016 and 2017 among men living with HIV and participating in the Ontario HIV Treatment Network Cohort Study. We calculated the proportion vaccinated against HPV, described vaccination experiences, and HPV vaccine knowledge, and calculated differences in characteristics between vaccinated and unvaccinated men. Among 1651 men (mean age = 51 years, 72% identified as gay), 7% were vaccinated (95% confidence interval[CI] 5.5-7.9%); 85% received their first dose at a primary care or HIV clinic. Among unvaccinated men, 40% were unaware of the HPV vaccine, 65% reported low perceived risk for HPV, and 8% discussed HPV vaccination with a physician. Compared to unvaccinated men, vaccinated men were younger, most identified as gay, had a higher education/income, reported a higher number of recent sex partners, and had a history of bacterial sexually transmitted infections (STIs), HPV, anogenital warts, and/or anal cancer. Our findings reveal that few men living with HIV were vaccinated against HPV. This may be influenced by low HPV awareness, prohibitive cost, and lack of physician recommendation. Several men reporting lower socio-economic status, older men, and heterosexual, bisexual, and other men who have sex with men were missed for vaccination. Primary care and HIV clinics may be ideal locations to increase uptake.


The effects of substance p on tendinopathy are dose-dependent: an in vitro and in vivo model study.
Substance P (SP) is known to be involved in neuropathic pain, chronic inflammation, and tendinopathy. The present study evaluated the effects of different doses of SP on tendon-derived stem cells (TDSCs) in vitro and tendons in vivo. For the in vitro study, TDSCs cultured in growth medium with different concentrations of SP (negative control, 0.1 nM, and 1.0 nM). The effects of SP on TDSCs were examined with respect to their ability to proliferate and differentiate. For the in vivo study, we injected different doses of SP (saline control, 0.5 nmol, and 5.0 nmol) into rat patella tendons to investigate the effects of SP on tendons. Low and high doses SP significantly enhanced the proliferation ability of TDSCs. Low-dose of SP induced the expression of tenocyte-related genes; however, high-dose of SP induced the expression of non-tenocyte genes, which was evident by the high expression of PPARγ and collagen type II. In the in vivo study, only high-doses of SP (5.0 nmol) induced the tendinosis-like changes in the patella tendon injection model. Low doses of SP (0.5 nmol) enhanced the tenogenesis compared with saline injection and the high-dose SP group. SP enhances the proliferation of TDSCs in vitro and the effects of SP on tendinopathy are dose-dependent in vivo.


Clozapine safety monitoring and related research in psychiatry and neurology in South America: A scoping review.
The quality and quantity of clozapine safety monitoring considerably differs among South American countries and mainly focus on hematological surveillance. Few studies have been conducted on other clozapine-related adverse effects (ADRs) and mainly refer to case reports and literature reviews. We retrieved thirty-nine publications on clozapine related ADRs others than neutropenia. Studies in Brazil and Venezuela accounted for 67 % of all the publications, and 8 out of 12 countries published 2 or less manuscripts. Only Chile offers serum clozapine level measurement in public institutions. Given the recently recognized role of ethnicity, gender, smoking, obesity drug interactions in optimal clozapine administration, modernization of clozapine clinical use and research in psychiatry and neurology most be broadcasted and stimulated in South American countries.


The associations between the polymorphisms in the CTLA-4 gene and the risk of Graves' disease in the Chinese population.
The associations between the polymorphisms in Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4) gene and Graves' disease (GD) have been extensively investigated in Chinese population. However, the results were inconsistent. The objective of this study is to investigate the associations between the polymorphisms in CTLA-4 gene and the risk of GD by meta-analysis. We searched Pubmed database, Medline (Ovid) database, CNKI database and Wanfang database, covering all studies until August 11, 2012. Statistical analysis was performed by using the Revman4.2 software and the Stata10.0 software. A total of 28 case-control studies concerning the most widely studied three polymorphisms [+49A/G(rs231775), -318C/T(rs5742909) and CT60(rs3087243)] for Chinese population in 21 publications were included. The results suggested that the G allele carriers (GG+GA) might have an increased risk of GD when compared with the AA homozygote carriers for the +49A/G polymorphism (GG+GA vs. AA: OR = 2.57, 95%CI = 1.87-3.52). However, as to the -318C/T polymorphism and CT60 polymorphism, the results indicated that the variant allele carriers might have decreased risks of GD when compared with the homozygote carriers (-318C/T: TT+TC vs. CC: OR = 0.78, 95%CI = 0.62-0.97; CT60: AA+AG vs. GG: OR = 0.64, 95%CI = 0.52-0.78). The current meta-analysis indicated that the polymorphisms in the CLTA-4 gene might be risk factors for GD in the Chinese population. In future, more large-scale case-control studies are needed to validate these results.


Design, Synthesis, EPR-Studies and Conformational Bias of Novel Spin-Labeled DCC-Analogues for the Highly Regioselective Labeling of Aliphatic and Aromatic Carboxylic Acids.
Novel types of spin-labeled N,N'-dicyclohexylcarbodiimides (DCC) are reported that bear a 2,2,6,6-tetramethylpiperidinyloxyl (TEMPO) residue on one side and different aromatic and aliphatic cyclohexyl analogues on the other side of the diimide core. These readily available novel reagents add efficiently to aliphatic and aromatic carboxylic acids, forming two possible spin-labeled amide derivatives with different radical distances of the resulting amide. The addition of aromatic DCC analogues proceeds with excellent selectivity, giving amides where the carboxylic acid is exclusively connected to the aromatic residue, while little or no selectivity was observed for the aliphatic congeners. The usefulness of these adducts in structural studies was demonstrated by EPR (electron paramagnetic resonance) measurements of biradical adducts of biphenyl-4,4'-dicarboxylic acids. These analyses also reveal high degrees of conformational bias for aromatic DCC derivatives, which further underlines the powerfulness of these novel reagents. This observation was further corroborated by quantum chemical calculations, giving a detailed understanding of the structural dynamics, while detailed information on the solid state structure of all novel reagents was obtained by X-ray structure analyses.


Fine mapping of a susceptibility locus for bipolar and genetically related unipolar affective disorders, to a region containing the C21ORF29 and TRPM2 genes on chromosome 21q22.3.
Linkage analyses of bipolar families have confirmed that there is a susceptibility locus near the telomere on chromosome 21q. To fine map this locus we carried out tests of allelic association using 30 genetic markers near the telomere at 21q22.3 in 600 bipolar research subjects and 450 ancestrally matched supernormal control subjects. We found significant allelic association with the microsatellite markers D21S171 (P=0.016) and two closely linked single-nucleotide polymorphisms, rs1556314 (P=0.008) and rs1785467 (P=0.025). A test of association with a three locus haplotype across the susceptibility region was significant with a permutation test of P=0.011. A two SNP haplotype was also significantly associated with bipolar disorder (P=0.01). Only two brain expressed genes, TRPM2 and C21ORF29 (TSPEAR), are present in the associated region. TRPM2 encodes a calcium channel receptor and TSPEAR encodes a peptide with repeats associated with epilepsy in the mouse. DNA from subjects who had inherited the associated marker alleles was sequenced. A base pair change (rs1556314) in exon 11 of TRPM2, which caused a change from an aspartic acid to a glutamic acid at peptide position 543 was found. This SNP showed the strongest association with bipolar disorder (P=0.008). Deletion of exon 11 of TRPM2 is known to cause dysregulation of cellular calcium homeostasis in response to oxidative stress. A second nonconservative change from arginine to cysteine at position 755 in TRPM2 (ss48297761) was also detected. A third nonconservative change from histidine to glutamic acid was found in exon 8 of TSPEAR. These changes need further investigation to establish any aetiological role in bipolar disorder.


Is the motivational effect of opiate withdrawal reflected by common somatic indices of precipitated withdrawal? A place conditioning study in the rat.
Rats implanted for 5 days with a morphine pellet were dosed once with naltrexone (subcutaneous, s.c.) or methylnaltrexone (intraventricular, i.c.v.). Then the rats were observed for several somatic signs of precipitated withdrawal and tested for aversion to the place of the withdrawal. The two antagonist treatments produced different withdrawal syndromes, but both were associated with a place aversion which followed a simple monophasic function of the dose of antagonist. More importantly, there was an absence of any overall relation between individual withdrawal signs (jumping, writhing, shaking, diarrhea, and weight loss) and the aversive effect seen. It was concluded, therefore, that the motivational impact of opiate abstinence is not always addressed in conventional models of withdrawal.


Recurrence of brain arteriovenous malformations in pediatric patients: a long-term follow-up study.
Previously thought to be congenital, AVMs have shown evidence of de-novo formation and continued growth, thus shifting thoughts on their pathophysiology. Pediatric AVM patients have been reported to be more prone to develop AVM recurrence after a seemingly complete cure. Therefore, we assessed the risk of AVM treated in childhood to recur in adulthood after a long-term follow-up in our own cohort. Control DS-angiography was arranged during 2021-2022 as part of a new protocol for all AVM patients who were under 21 years of age at the time of their treatment and in whom the treatment had occurred at least five years earlier. Angiography was offered only to patients under 50 years of age at the time of the new protocol. The complete eradication of AVM after the primary treatment had been originally confirmed with DSA in every patient. A total of 42 patients participated in the late DSA control, and 41 of them were included in this analysis after excluding the patient diagnosed with HHT. The median age at the time of admission for AVM treatment was 14.6 (IQR 12-19, range 7-21 years) years. The median age at the time of the late follow-up DSA was 33.8 years (IQR 29.8-38.6, range 19.4-47.9 years). Two recurrent sporadic AVMs and one recurrent AVM in a patient with hereditary hemorrhagic telangiectasia (HHT) were detected. The recurrence rate was 4.9% for sporadic AVMs and 7.1% if HHT-AVM was included. All the recurrent AVMs had originally bled and been treated microsurgically. The patients with sporadic AVM recurrence had been smoking their whole adult lives. Pediatric and adolescent patients are prone to develop recurrent AVMs, even after complete AVM obliteration verified by angiography. Therefore, imaging follow-up is recommended.


Characteristics and predictors associated with cancer-related fatigue among solid and liquid tumors.
Cancer-related fatigue (CRF) is a devastating complication with limited recognized clinical risk factors. We examined characteristics among solid and liquid cancers utilizing Machine learning (ML) approaches for predicting CRF. We utilized 2017 National Inpatient Sample database and employed generalized linear models to assess the association between CRF and the outcome of burden of illness among hospitalized solid and non-solid tumors patients. And further applied lasso, ridge and Random Forest (RF) for building our linear and non-linear ML models. The 2017 database included 196,330 prostate (PCa), 66,385 leukemia (Leuk), 107,245 multiple myeloma (MM), and 41,185 cancers of lip, oral cavity and pharynx (CLOP) patients, and among them, there were 225, 140, 125 and 115 CRF patients, respectively. CRF was associated with a higher burden of illness among Leuk and MM, and higher mortality among PCa. For the PCa patients, both the test and the training data had best areas under the ROC curve [AUC = 0.91 (test) vs. 0.90 (train)] for both lasso and ridge ML. For the CLOP, this was 0.86 and 0.79 for ridge; 0.87 and 0.84 for lasso; 0.82 for both test and train for RF and for the Leuk cohort, 0.81 (test) and 0.76 (train) for both ridge and lasso. This study provided an effective platform to assess potential risks and outcomes of CRF in patients hospitalized for the management of solid and non-solid tumors. Our study showed ML methods performed well in predicting the CRF among solid and liquid tumors.


Beta-endorphin immunoreactivity during high-intensity exercise with and without opiate blockade.
Nine highly fit men [mean (SE) maximum oxygen uptake, VO2max: 63.9 (1.7) ml x kg(-1) x min(-1); age 27.6 (1.6) years] were studied during two treadmill exercise trials to determine plasma beta-endorphin immunoreactivity during intense exercise (80% VO2max). A double-blind experimental design was used, and subjects performed the two exercise trials in counterbalanced order. Exercise trials were 30 min in duration and were conducted 7 days apart. One exercise trial was undertaken following administration of naloxone (1.2 3 cm3) and the other after receiving a placebo (0.9% NaCl saline; 3 cm3). Prior to each experimental trial, a flexible catheter was placed into an antecubital vein and baseline blood samples were collected. Thereafter, each subject received either a naloxone or placebo bolus injection. Blood samples were also collected after 10, 20 and 30 min of continuous exercise. beta-Endorphin was higher (P < 0.05) during exercise when compared to pre-exercise in both trials. However, no statistically significant difference was found (P> 0.05) between exercise time points within either experimental trial. beta-endorphin immunoreactivity was greater (P < 0.05) in the naloxone than in the placebo trial during each exercise sampling time point [10 min: 63.7 (3.9) pg x ml(-1) vs 78.7 (3.8) pg x ml(-1); 20 min: 68.7 (4.1) pg x ml(-1) vs (4.3) pg x ml(-1); 30 min: 71.0 (4.3) pg x ml(-1) vs 82.5(3.2) pg x ml(-1)]. These data suggest that intense exer induces significant increases in beta-endorphin that are maintained over time during steady-rate exercise. Exercise and naloxone had an interactive effect on beta-endorphin release that warrants further investigation.


[The preparation of rabbit antiserum against gekko japonicus Hoxc10 and it's property identification].
Prepare the rabbit antiserum against gecko japonicus Hoxc10 and to identify its properties. Prokaryotic expression vector of g-Hoxc10 were constructed and then transform into E.coli (BL21). To make GST-g-Hoxc10 fusion protein in E.coli (BL21) under the optimized induction of Isopropyl β-D-1-thiogalactopyranoside(IPTG). The recombination proteins were purified using affinity chromatography. The purified fusion protein was inoculated into adult rabbits to develop antiserum. Western blot and immunohistochemistry staining were then performed to evaluate the feature of the prepared antiserum. Prokaryotic expression vectors of g-Hoxc10 were successfully constructed. The soluble recombinant protein was highly expressed in E.coli BL21 and inoculated into adult rabbits to obtain high titer antiserum. Western blot and immunohistochemistry staining were then performed to evaluate the specificity of the prepared antiserum. We successfully amplified and expressed the g-Hoxc10 in E.coli BL21. The purified fusion protein was inoculated into adult rabbits to develop antiserum. The obtained antiserum of g-Hoxc10 showed a high titer against Hoxc10 proteins. The protein and antiserum prepared in this study can be used for further research of the function investigation of Hoxc10.


A novel online platform promotes asynchronous class preparation and thought transparency.
Engaging all learners with self-directed class preparation materials can be challenging. The purpose of this study is to assess student perceptions of a novel app and web-based program, Practice Improvement using Virtual Online Training (PIVOT) as a preparatory tool in a pharmacy therapeutics course. PIVOT was designed to encourage self-directed information gathering, group collaboration, and problem-solving prior to classes. Students accessed PIVOT to obtain patient information and provide responses to questions. A semi-structured large group case discussion, facilitated by the instructor, followed the preparatory assignment. All students were invited to participate in pre-/post-activity online surveys to evaluate their experiences. One hundred and ten students (92.4%) completed both surveys. Students identified viewing/comparing answers with classmates (73%), enforcing preparation (51%), and asynchronous preparation (51%) as useful aspects of PIVOT. Working with a group (42%) and organizing patient information (32%) were selected as negative aspects of PIVOT. More than half of students preferred not to use PIVOT for class preparation, but 41% of students would like to see PIVOT integrated in their therapeutics courses. Integrating PIVOT into a pharmacy therapeutics course resulted in mixed student perceptions. Several helpful aspects of this platform were identified and a majority suggested drawbacks that are also common features of actual pharmacy practice. Implementing PIVOT in a different learning context may improve student perceptions.


Metformin sensitizes triple-negative breast cancer to proapoptotic TRAIL receptor agonists by suppressing XIAP expression.
Despite robust antitumor activity in diverse preclinical models, TNF-related apoptosis-inducing ligand (TRAIL) receptor agonists have not demonstrated efficacy in clinical trials, underscoring the need to identify agents that enhance their activity. We postulated that the metabolic stress induced by the diabetes drug metformin would sensitize breast cancer cells to TRAIL receptor agonists. Human triple (estrogen receptor, progesterone receptor, and HER2)-negative breast cancer (TNBC) cell lines were treated with TRAIL receptor agonists (monoclonal antibodies or TRAIL peptide), metformin, or the combination. The effects on cell survival, caspase activation, and expression of TRAIL receptors and the antiapoptotic protein XIAP were determined. In addition, XIAP was silenced by RNAi in TNBC cells and the effects on sensitivity to TRAIL were determined. The antitumor effects of metformin, TRAIL, or the combination were evaluated in an orthotopic model of metastatic TNBC. Metformin sensitized diverse TNBC cells to TRAIL receptor agonists. Metformin selectively enhanced the sensitivity of transformed breast epithelial cells to TRAIL receptor agonist-induced caspase activation and apoptosis with little effect on untransformed breast epithelial cells. These effects of metformin were accompanied by robust reductions in the protein levels of XIAP, a negative regulator of TRAIL-induced apoptosis. Silencing XIAP in TNBC cells mimicked the TRAIL-sensitizing effects of metformin. Metformin also enhanced the antitumor effects of TRAIL in a metastatic murine TNBC model. Our findings indicate that metformin enhances the activity of TRAIL receptor agonists, thereby supporting the rationale for additional translational studies combining these agents.


Immobilized arginine/tryptophan-rich cyclic dodecapeptide on reduced graphene oxide anchored with manganese dioxide for microbial biofilm eradication.
To avoid the accumulation of bacterial biofilms in water pipelines, it is critical to develop potent antimicrobial agents with good ability to reduce extracellular polymeric substances (EPS). In this study, cyclic dodecapeptides were synthesized, and different mutations for increasing the ratio of arginine (Arg) and tryptophan (Trp) were introduced. Separately, the synthesized dodecapeptides were immobilized on a reduced graphene oxide nanocomposite anchored with a hierarchical β-MnO2 (RGO/β-MnO2) hybrid. With a minimum inhibitory concentration of 0.97 g/mL, the immobilized Arg-Trp rich antimicrobial peptides (AMP) on RGO/MnO2 nanocomposite, Cdp-4/RGO/MnO2, showed superior efficacy against multidrug-resistant Pseudomonas aeruginosa ATCC 15692 (P. aeruginosa) planktonic cells. The immobilized Cdp-4/RGO/β-MnO2 also eradicated the mature biofilm by 99% with a minimum inhibitory concentration value of 62.5 µg/mL with significant reduction of EPS. These characteristics allow the use of the immobilized Arg-Trp rich AMP as a promising antimicrobial agent against microbial biofilms, present in water distribution systems.


Erratum: A comparative evaluation of fracture resistance of endodontically treated teeth using four different intraorifice barriers: An in vitro study.
[This corrects the article on p. 420 in vol. 22, PMID: 33082655.].


Current and future antiviral therapy of severe seasonal and avian influenza.
The currently circulating H3N2 and H1N1 subtypes of influenza A virus cause a transient, febrile upper respiratory illness in most adults and children ("seasonal influenza"), but infants, the elderly, immunodeficient and chronically ill persons may develop life-threatening primary viral pneumonia or complications such as bacterial pneumonia. By contrast, avian influenza viruses such as the H5N1 virus that recently emerged in Southeast Asia can cause severe disease when transferred from domestic poultry to previously healthy people ("avian influenza"). Most H5N1 patients present with fever, cough and shortness of breath that progress rapidly to adult respiratory distress syndrome. In seasonal influenza, viral replication remains confined to the respiratory tract, but limited studies indicate that H5N1 infections are characterized by systemic viral dissemination, high cytokine levels and multiorgan failure. Gastrointestinal infection and encephalitis also occur. The licensed anti-influenza drugs (the M2 ion channel blockers, amantadine and rimantadine, and the neuraminidase inhibitors, oseltamivir and zanamivir) are beneficial for uncomplicated seasonal influenza, but appropriate dosing regimens for severe seasonal or H5N1 viral infections have not been defined. Treatment options may be limited by the rapid emergence of drug-resistant viruses. Ribavirin has also been used to a limited extent to treat influenza. This article reviews licensed drugs and treatments under development, including high-dose oseltamivir; parenterally administered neuraminidase inhibitors, peramivir and zanamivir; dimeric forms of zanamivir; the RNA polymerase inhibitor T-705; a ribavirin prodrug, viramidine; polyvalent and monoclonal antibodies; and combination therapies.


Broadband and high-efficiency polarization conversion with a nano-kirigami based metasurface.
Nano-kirigami metasurfaces have attracted increasing attention due to their ease of three-dimension (3D) nanofabrication, versatile shape transformations, appealing manipulation capabilities and rich potential applications in nanophotonic devices. Through adding an out-of-plane degree of freedom to the double split-ring resonators (DSRR) by using nano-kirigami method, in this work we demonstrate the broadband and high-efficiency linear polarization conversion in the near-infrared wavelength band. Specifically, when the two-dimensional DSRR precursors are transformed into 3D counterparts, a polarization conversion ratio (PCR) of more than 90% is realized in wide spectral range from 1160 to 2030 nm. Furthermore, we demonstrate that the high-performance and broadband PCR can be readily tailored by deliberately deforming the vertical displacement or adjusting the structural parameters. Finally, as a proof-of-concept demonstration, the proposal is successfully verified by adopting the nano-kirigami fabrication method. The studied nano-kirigami based polymorphic DSRR mimic a sequence of discrete bulk optical components with multifunction, thereby eliminating the need for their mutual alignment and opening new possibilities.


Acid and alcohol tolerance of Escherichia coli O157:H7 in pulque, a typical Mexican beverage.
Pulque is a traditional Mexican fermented alcoholic beverage produced from the nectar of maguey agave plants. No data exist on the behavior of Escherichia coli O157:H7 in agave nectar and pulque. An initial trial was done of the behavior of E. coli O157:H7 during fermentation of nectar from a single producer, a nectar mixture from different producers and "seed" pulque. A second trial simulating artisanal pulque production was done by contaminating fresh nectar with a cocktail of three E. coli O157:H7 strains, storing at 16 ° and 22 °C for 14 h, adding seed pulque and fermenting until pulque was formed. A third trial used pulque from the second trial stored at 22 °C as seed to ferment fresh nectar at 22 °C for 48 h (fermentation cycle). This procedure was repeated for an additional two fermentation cycles. During incubation at 16 ° or 22 °C in the first trial, the E. coli O157:H7 strains multiplied in both the single producer nectar and nectar mixture, reaching maximum concentration at 12h. E. coli O157:H7 cell concentration then decreased slowly, although it survived at least 72 h in both fermented nectars. E. coli O157:H7 did not multiply in the seed pulque but did survive at least 72 h. In the second trial, the numbers of E. coli O157:H7 increased approximately 1.5 log CFU/ml at 22 °C and 1.2 log CFU/ml at 16 °C after 14 h. After seed pulque was added, E. coli O157:H7 concentration decreased to approximately 2 log CFU/ml, and then remained constant until pulque was produced. In the third trial, the E. coli O157:H7 cells multiplied and survived during at least three nectar fermentation cycles. The results suggest that E. coli O157:H7 can develop acid and alcohol tolerance in pulque, and constitutes a public health risk for pulque consumers.


Leveraging insights from behavioral economics to increase the value of health-care service provision.
United States health expenditures continue to escalate at unsustainable rates. A recent movement around increasing price transparency has been suggested as a way of reducing the rate of increase in expenditures, with legislative efforts taking place at both the state and federal level. While this seems on the surface like a good idea, simply providing information on prices to physicians, particularly trainees, may not achieve the type of large changes in practice patterns that proponents expect. The manner in which price transparency is implemented will likely play a significant role in its effectiveness as an intervention. In this article, the authors review efforts of transparency and default options from other contexts and leverage insights from behavioral economics to provide recommendations for increasing the likelihood that price transparency will lead to physicians weighing the relative value of interventions.


Involvement of caspase-3/PTEN signaling pathway in isoflurane-induced decrease of self-renewal capacity of hippocampal neural precursor cells.
Evidence has shown that children exposed to isoflurane anesthesia in early childhood display long-term cognitive abnormalities, and decreased self-renewal capacity of hippocampal neural precursor cells (NPCs), which are associated with cognition impairment. Caspase-3 has long been considered as a mediator in isoflurane-induced neuroapoptosis. However, accumulating data indicate that caspase-3 also plays a non-apoptotic negative regulatory role in NPCs self-renewal. In this study we used in vitro NPC cultures to test whether caspase-3 and its downstream signaling effectors were involved in isoflurane-induced impairment of the self-renewal capacity of hippocampal NPCs. We showed that isoflurane exposure induced a decrease in the self-renewal capacity of hippocampal NPCs by decreasing proliferation and increasing neuronal differentiation. Furthermore, we found that isoflurane exposure significantly increased the levels of active caspase-3 and decreased the levels of phospho-PTEN under both proliferation and differentiation conditions. Inhibition of either caspase-3 with Z-DEVD-fmk or PTEN with BPV (phen) in NPCs, attenuated the isoflurane-induced decrease of their proliferation and increase of neuronal differentiation. Application of Z-DEVD-fmk also attenuated isoflurane-induced decrease in phospho-PTEN expression. Taken together, our in vitro results reveal a previously uncharacterized involvement of caspase-3/PTEN signaling in the isoflurane-induced impairment of NPCs self-renewal, and contribute to the identification of novel targets for maintaining NPCs self-renewal in isoflurane-induced cognitive dysfunction.


Outcome impact of PIK3CA mutations in HER2-positive breast cancer patients treated with trastuzumab.
Phosphatidylinositol 3-kinase (PI3K) pathway activation has been suggested to negatively influence response to anti-HER2 therapy in breast cancer patients. The present study focused on mutations of the PIK3CA gene, encoding one of the two PI3K subunits. PIK3CA mutations were assessed by direct sequencing in 80 HER2-positive patients treated with 1 year of trastuzumab. All patients preoperatively received four cycles of anthracycline-based chemotherapy, followed by four cycles of docetaxel and 1 year of trastuzumab, starting either before surgery with the first cycle of docetaxel and continuing after surgery (neoadjuvant trastuzumab arm, n=43), or only after surgery (adjuvant trastuzumab arm, n=37). PIK3CA mutations were found in 17 tumours (21.3%). Better disease-free survival (DFS) was observed in patients with PIK3CA wild-type compared with mutated tumours (P=0.0063). By combining PIK3CA status and treatment arms, four separate prognostic groups with significantly different DFS (P=0.0013) were identified. These results confirm that the outcome of HER2-positive patients treated with trastuzumab is significantly worse in patients with PIK3CA-mutated compared with wild-type tumours.


[Changes in the water-electrolyte and protein balance of the body in acute gastrointestinal ulcerative hemorrhage].
The authors studied 127 patients, divided into 4 groups, relating to the haemorrhage stage in accordance with the classification of Lutsevich. It has been established that there exist changes in the hydroelectrolytic and protein balance of the patients having acute gastrointestinal ulcerative haemorrhage.


The process of building European university alliances: a rhizomatic analysis of the European Universities Initiative.
Drawing upon French philosophy, this study offers a novel empirical and conceptual understanding of the newly launched European Universities Initiative. In 2019, higher education institutions across the European Union created 17 new alliances as part of the first pilot phase of the initiative. This is an experiment in European and global higher education. This paper offers a conceptual contribution to the field of higher education studies, making use of a rhizomatic analysis to explore how university alliances build what the European Commission refers to as the 'European universities of the future.' Based on the conceptual reflection and findings from a small-scale empirical study, this paper concludes that the alliances within the European Universities Initiative rely on pre-existing higher education and research partnerships while at the same time experimenting to foster a diversity of institutional forms to achieve the ambitious goal of creating 'European Universities.'


From Life in the Sea to the Clinic: The Marine Drugs Approved and under Clinical Trial.
In the last decades Blue Growth policy in european and non-european countries produced a great impulse in applied marine sciences, comprehending the research of new bioactive molecules in marine organisms. These organisms are a great source of natural compounds with unique features resulting from the huge variability of marine habitats and species living in them. Most of the marine compounds in use and in clinical trials are drugs for cancer therapy and many of them are conjugated to antibody to form antibody-drug conjugates (ADCs). Severe pain, viral infections, hypertriglyceridemia, obesity, Alzheimer's and other CNS diseases are further target conditions for these pharmaceuticals. This review summarizes the state-of-the-art marine drugs focusing on the most successful results in the fast expanding field of marine pharmacology.


Development of photoreceptor-specific promoters and their utility to investigate EIAV lentiviral vector mediated gene transfer to photoreceptors.
We wanted to investigate the ability of recombinant equine infectious anemia virus (EIAV) vectors to transduce photoreceptor cells by developing a series of photoreceptor-specific promoters that drive strong gene expression in photoreceptor cells. Promoter fragments derived from the rhodopsin (RHO), the beta phosphodiesterase (PDE) and the retinitis pigmentosa (RP1) genes were cloned in combination with an enhancer element, derived from the interphotoreceptor retinoid-binding protein gene (IRBP), into luciferase reporter plasmids. An in vitro transient reporter assay was carried out in the human Y-79 retinoblastoma cell line. The optimal promoters from this screen were then cloned into the recombinant EIAV vector for evaluation in vivo following subretinal delivery into mice. All promoters maintained a photoreceptor-specific expression profile in vitro and the gene expression was further enhanced in combination with the IRBP enhancer. The use of IRBP-combined RHO or PDE promoters showed modest but exclusive expression in photoreceptors following subretinal delivery to mice. By contrast an EIAV vector containing the cytomegalovirus (CMV) promoter drove reporter gene expression in both photoreceptors and retinal pigment epithelium. It may be possible to use recombinant EIAV vectors containing photoreceptor-specific promoters to drive therapeutic gene expression to treat a range of retinal degenerative diseases where the photoreceptor cell is the primary disease target.


Initial evaluation of a 290-microm diameter subcutaneous glucose sensor: glucose monitoring with a biocompatible, flexible-wire, enzyme-based amperometric microsensor in diabetic and nondiabetic humans.
Results of the initial clinical evaluation in 20 human subjects of a subcutaneously implanted microsensor-based amperometrically glycemia-monitoring system, carried out between April 1994 and June 1995, are reported. The system was based on the electrical connection ("wiring") of the reaction centers of glucose oxidase to a gold electrode and on elimination of the chemicals that interfere with glucose monitoring through their horseradish peroxidase-catalyzed oxidation by internally generated hydrogen peroxide. The sensor was finer than a 29-gauge needle and had no leachable components. Because of its high selectivity for glucose, the sensor output was virtually nil at zero glucose level. This enables prompt "one-point" in vivo calibration of the sensor with a single blood glucose sample. Microsensors were subcutaneously implanted in ten nondiabetic and ten insulin-dependent diabetes mellitus (IDDM) volunteers. All subjects underwent standard meal tests and intravenous glucose-tolerance tests (IVGTT) in addition to hourly plasma glucose measurements. The sensor signals were continuously recorded, and the glucose concentration estimates were derived by calibrating the sensor using a single blood sample (one-point calibration). Regression analysis revealed that the sensor-estimated glucose concentrations were linearly related to the plasma glucose concentrations (r2 = 0.75) over a wide glucose concentration range (2-28 mmol/L) (sensor estimate = plasma 0.96 + 0.26 mmol/L). The difference between the estimated and actual glucose concentration was -0.13+/-0.23 mmol/L [mean +/-95% confidence interval (CI), n = 546], and 95% of the estimates fell in clinically acceptable zones of the Clarke error grid. The sensing delay time was 10.4+/-2.3 min as measured by the IVGTT. The subjects reported no discomfort associated with wearing the sensors.


Perspective on recent developments on sulfur-containing agents and hydrogen sulfide signaling.
The last couple of years have witnessed the coming together of several initially unconnected lines of investigation which now link natural sulfur products to hydrogen sulfide release and wide ranging cardiovascular protection. It has become apparent that sulfur compounds contained within garlic, onions, mushrooms and various edible beans and fruits may be transformed chemically or enzymatically in the human body with subsequent formation of hydrogen sulfide. The latter has emerged during the last decade from a shadowy existence as toxic gas to be recognized as the third gaseous transmitter besides nitric oxide ( (.)NO) and carbon monoxide (CO). Hydrogen sulfide is formed endogenously in the human body by enzymes such as cystathionine beta-synthase (CBS) in the brain and cystathionine gamma-lyase (CSE) in liver, vascular and non-vascular smooth muscle. Although its exact chemical and biochemical modes of action are still not fully understood, levels of hydrogen sulfide in the brain and vasculature have unambiguously been associated with human health and disease. Not surprisingly, agents releasing hydrogen sulfide, as well as inhibitors of hydrogen sulfide synthesis (CBS and CSE inhibitors) have been investigated. Apart from linking our daily diet to a healthy brain and cardiovasculature, these findings may also provide new leads for drug design. Future studies will therefore need to focus on how such compounds are formed and transformed in the relevant plants, how food processing affects their chemical constitution, and how they release hydrogen sulfide (or control its levels) in the human body. Such multidisciplinary research should ultimately answer the all-important question if a hearty diet is also good for the heart.


An artificial intelligence-based approach for identifying rare disease patients using retrospective electronic health records applied for Pompe disease.
We retrospectively screened 350,116 electronic health records (EHRs) to identify suspected patients for Pompe disease. Using these suspected patients, we then describe their phenotypical characteristics and estimate the prevalence in the respective population covered by the EHRs. We applied Symptoma's Artificial Intelligence-based approach for identifying rare disease patients to retrospective anonymized EHRs provided by the "University Hospital Salzburg" clinic group. Within 1 month, the AI screened 350,116 EHRs reaching back 15 years from five hospitals, and 104 patients were flagged as probable for Pompe disease. Flagged patients were manually reviewed and assessed by generalist and specialist physicians for their likelihood for Pompe disease, from which the performance of the algorithms was evaluated. Of the 104 patients flagged by the algorithms, generalist physicians found five "diagnosed," 10 "suspected," and seven patients with "reduced suspicion." After feedback from Pompe disease specialist physicians, 19 patients remained clinically plausible for Pompe disease, resulting in a specificity of 18.27% for the AI. Estimating from the remaining plausible patients, the prevalence of Pompe disease for the greater Salzburg region [incl. Bavaria (Germany), Styria (Austria), and Upper Austria (Austria)] was one in every 18,427 people. Phenotypes for patient cohorts with an approximated onset of symptoms above or below 1 year of age were established, which correspond to infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD), respectively. Our study shows the feasibility of Symptoma's AI-based approach for identifying rare disease patients using retrospective EHRs. Via the algorithm's screening of an entire EHR population, a physician had only to manually review 5.47 patients on average to find one suspected candidate. This efficiency is crucial as Pompe disease, while rare, is a progressively debilitating but treatable neuromuscular disease. As such, we demonstrated both the efficiency of the approach and the potential of a scalable solution to the systematic identification of rare disease patients. Thus, similar implementation of this methodology should be encouraged to improve care for all rare disease patients.


Binding of sialyl Lewis X antigen to lectin-like receptors on NK cells induces cytotoxicity and tyrosine phosphorylation of a 17-kDa protein.
Natural killer (NK) cells mediate cytotoxicity through cell-surface receptors including lectin-like receptors. We have investigated whether sialyl Lewis X (sLe(X)) antigen, Neu5Acalpha2,3Galbeta1,4(Fucalpha1,3) GlcNAc-R, can bind to the lectin-like receptors on human NK-derived KHYG cells, using transferrin secreted by human hepatoma-derived HepG2 cells (Hep-TF), whose N-glycans are rich in alpha1,3-fucosylated bi-, tri-, and tetra-antennary type complexes, and commercially available human transferrin (Nor-TF), which is comprised of bi-antennary N-glycans without alpha1,3-fucosylation. High sLeX-expressing erythroleukemia-derived K562 cells isolated from fucosyltransferase-3-transfected cells were 2.5-fold more susceptible than wild-type K562 cells to KHYG cells. Fluorescein isothiocyanate (FITC)-labeled Hep-TF bound 1.8-fold more strongly to KHYG cells than did FITC-labeled Nor-TF; the binding was suppressed by treatment with anti-NKG2D, anti-NKG2C, anti-CD94 and anti-CD161 antibodies. FITC-labeled Hep-TF bound more strongly to human monocyte-derived U937 cells transfected with NKG2D and CD94 than to wild-type U937 cells. Moreover, tyrosine phosphorylation of a 17-kDa protein in the KHYG cells was enhanced by incubation on a Hep-TF coated plate and treatment with an anti-NKG2D antibody, but not by a Nor-TF coated plate and an anti-CD94 antibody. The interaction of sLe(X) antigen with lectin-like receptors on NK cells induces cytotoxicity that is mediated through a tyrosine-phosphorylated 17-kDa protein.


Identification of a 5 bp duplicate in the AP1S2 gene of an individual with X-linked intellectual disability.
Adaptor-related protein complex 1 subunit sigma 2 (AP1S2) is a subunit of AP1 that is crucial for the reformation of the synaptic vesicle. Variants in AP1S2 have been reported to cause a rare neurodevelopmental disorder, Pettigrew syndrome (PGS) (OMIM: 304,340), which is characterized by walking delay, abnormal speech, mild to profound X-linked intellectual disability (XLID), and abnormal brain, and behaviors. Here, we describe a 2-year- and 5-month-old male patient who presented with global developmental delay (GDD). Trio whole exome sequencing (WES) revealed a 5 bp duplicate in the AP1S2 gene (NM_003916.5: exon 2: c.96_100dup, p. Leu34Glnfs*8) predicted to cause early termination of translation, which was inherited from the unaffected mother. The clinical features of our patient were consistent with previous reports. This is the second case in the Chinese family and the eleventh variant found in AP1S2-related XLID. Our findings expand the AP1S2 variant spectrum in neurodevelopmental disorders and provide evidence for the application of WES in PGS diagnosis.


Randomized controlled trial of vacuum therapy for intermittent claudication.
The "gold standard" treatment of intermittent claudication (IC) is supervised exercise therapy (SET). Intermittent vacuum therapy (IVT) has recently been promoted as an additional treatment of IC. During IVT, negative pressure and atmospheric pressure are alternatingly applied to the lower extremities, possibly resulting in improved circulation. The aim of this study was to determine a potential additional effect of IVT in IC patients undergoing a standardized SET program. IC patients were recruited from three Dutch general hospitals between December 2015 and July 2017. They received a standardized SET program but were also randomly assigned to an intervention group receiving an IVT treatment (-50 mBar negative pressure) or a control group receiving a sham treatment (-5 mBar negative pressure). IVT was provided in a dedicated clinic during 12 sessions of 30 minutes during a 6-week period. The primary outcome measure was a change in maximal treadmill walking distance. Secondary outcome measures were a change in functional treadmill walking distance, 6-minute walk test, ambulatory ability, and quality of life. A total of 78 patients were randomized, of whom 70 were available for intention-to-treat analysis (control, n = 34; intervention, n = 36). At 6 and 12 weeks, increases in walking distance were of equal magnitude. Median (interquartile range) change in maximal treadmill walking distance during 12 weeks was +335 (205-756) meters in control patients and +250 (77-466) meters in intervention patients (P = .109), whereas functional treadmill walking distance increased +230 (135-480) meters and +188 (83-389) meters (P = .233), respectively. Mean ± standard deviation change in the 6-minute walk test was +36 ± 48 meters and +55 ± 63 meters (P = .823), respectively. Ambulatory ability and quality of life improved equally in both groups. IVT does not confer any additional beneficial effects in IC patients undergoing a standardized SET program.


Naphthalimide-based a highly selective two-photon fluorescent probe for imaging of hydrogen sulfide in living cells and inflamed tissue of mouse model.
Hydrogen sulfide (H2S) is a very important third endogenously generated gaseous signaling molecule and plays a key role in physiological and pathological regulation processes of living biosystems. Although a lot of H2S fluorescent probes have been reported, the relationship between the physiology and pathology of H2S in inflamed tissues remains unclear. Herein, by adopting a donor-π-acceptor (D-π-A)-structured naphthalimide derivative as the two-photon (TP) fluorophore and a 4-dinitrobenzene-ether (DNB) with a strong intramolecular charge transfer (ICT) effect as the recognition moiety, we reported a novel TP bioimaging probe NP-H2S for H2S with improved sensitivity. The NP-H2S exhibits very low background fluorescence in the absence of H2S, and a significant 258-fold fluorescence intensity enhancement was observed in the presence of H2S, resulting in a high sensitivity and selectivity to H2S in aqueous solutions with a detection limit of 18.8 nM observed. The probe also shows a wide linear response concentration range (0-10.0 μM) to H2S with high selectivity. All these features are favorable for direct monitoring of H2S in complex biological samples. It was then applied for direct TP imaging of H2S in tissues of inflammation model with satisfactory sensitivity, indicating it has the latent capability in further biological applications for investigation of the interaction H2S with inflammation.


Comparison of machine learning models and CEUS LI-RADS in differentiation of hepatic carcinoma and liver metastases in patients at risk of both hepatitis and extrahepatic malignancy.
CEUS LI-RADS (Contrast Enhanced Ultrasound Liver Imaging Reporting and Data System) has good diagnostic efficacy for differentiating hepatic carcinoma (HCC) from solid malignant tumors. However, it can be problematic in patients with both chronic hepatitis B and extrahepatic primary malignancy. We explored the diagnostic performance of LI-RADS criteria and CEUS-based machine learning (ML) models in such patients. Consecutive patients with hepatitis and HCC or liver metastasis (LM) who were included in a multicenter liver cancer database between July 2017 and January 2022 were enrolled in this study. LI-RADS and enhancement features were assessed in a training cohort, and ML models were constructed using gradient boosting, random forest, and generalized linear models. The diagnostic performance of the ML models was compared with LI-RADS in a validation cohort of patients with both chronic hepatitis and extrahepatic malignancy. The mild washout time was adjusted to 54 s from 60 s, increasing accuracy from 76.8 to 79.4%. Through feature screening, washout type II, rim enhancement and unclear border were identified as the top three predictor variables. Using LI-RADS to differentiate HCC from LM, the sensitivity, specificity, and AUC were 68.2%, 88.6%, and 0.784, respectively. In comparison, the random forest and generalized linear model both showed significantly higher sensitivity and accuracy than LI-RADS (0.83 vs. 0.784; all P < 0.001). Compared with LI-RADS, the random forest and generalized linear model had higher accuracy for differentiating HCC from LM in patients with chronic hepatitis B and extrahepatic malignancy.


Epidermal growth factor receptor directed therapy in head and neck cancer.
Squamous cell head and neck cancer (SCCHN) is the seventh most common cause of cancer death worldwide and its incidence is rising rapidly in developing countries. Despite recent advances in managing locally advanced SCCHN, patients with recurrent and metastatic SCCHN have a poor prognosis and little progress has been made its management. Epidermal growth factor receptor (EGFR) has been implicated in the pathogenesis of SCCHN and is a marker of poor prognosis. Recent advances in targeted therapeutics against EGFR are being investigated clinically. In this article, we review the different modalities utilized to inhibit EGFR signaling in SCCHN, including small molecule tyrosine kinase inhibitors, monoclonal antibodies, anti-sense therapy and immunotoxin conjugates. Monotherapy with EGFR inhibitors has demonstrated response rates between 5 and 15% in advanced SCCHN. However, combining EGFR inhibitors with cytotoxic chemotherapy or radiation therapy appears to augment response rates and survival. With the foundation for the use of EGFR inhibitors laid in these studies, future studies will need to optimize the delivery of these agents in combination with conventional therapies.


High concentrations of Porphyromonas gingivalis-LPS downregulate Tlr4 and modulate phosphorylation of ERK and AKT in murine cementoblasts.
Porphyromonas gingivalis lipopolysaccharide (PG-LPS) is an important virulence factor potentially contributing to periodontal tissue destruction. Toll-like receptor 4 (Tlr4) is a key mediator of NF-kB activation during pathogen recognition. Previous work using Tlr4-specific antibodies demonstrated a partial neutralization of PG-LPS effects on murine cementoblasts, which can affect cell function and regulate gene expression of osteoclastic markers. PG-LPS also potentially influence the inflammation process and the resorption of mineralized tissues. Yet, such inflammatory responses and cell signaling events remain to be characterized at the protein level. We thus investigated the effect of 1 and 10 µg/ml of PG-LPS, respectively, on cell morphology, cell viability, and selected key downstream molecules of the Tlr4 signaling cascade in cementoblasts. High concentrations of PG-LPS (10 µg/ml) significantly reduced cell viability after 48 h. Upon PG-LPS-stimulation, Tlr4 was significantly downregulated. Equally, IκBα, a downstream molecule, was downregulated in terms of phosphorylation and protein production. Furthermore, downstream signaling kinases, like serine/threonine kinase phospho-AKT and the mitogen-activated protein kinase (MAPK)-family, specifically phospho-ERK1/2, were significantly upregulated under high PG-LPS-concentrations. We provide new insights into PG-LPS-triggered intracellular signaling pathways in cementoblasts and thus deliver a basis for further research in PG-mediated periodontal inflammation.


IgG1 and IgG2 are the predominant subclasses of antiphospholipid antibody in women with the lupus anticoagulant.
We studied the sera of 36 patients with lupus anticoagulant and IgG antibodies against both phosphatidylserine and cardiolipin. Most sera also had IgG antibodies against other phospholipids: 97% against phosphatidylinositol, 91% against phosphatidylglycerol, and 82% against phosphatidylethanolamine. IgG2 was the predominant subclass against cardiolipin and phosphatidylserine; 35 of 36 patients (98%) had IgG2 against both phospholipids. Most patients also had the IgG1 subclass; 32 of 36 (89%) against cardiolipin and 25 of 36 (69%) against phosphatidylserine. IgG3 and IgG4 subclasses were present at very low concentrations and in only a minority of the sera. The antibody response against phosphatidylserine was characterized by significantly less IgG1 than was the response against cardiolipin (P less than 0.01), although the IgG2 responses against each phospholipid were not different. IgG subclasses were unrelated to any other aspect of the patients' history, including a history of thrombocytopenia or thrombosis, a positive antinuclear antibody test, or a diagnosis of systemic lupus erythematosus.


Microglial depletion using intrahippocampal injection of liposome-encapsulated clodronate in prolonged hypothermic cardiac arrest in rats.
Trauma patients who suffer cardiac arrest (CA) from exsanguination rarely survive. Emergency preservation and resuscitation using hypothermia was developed to buy time for resuscitative surgery and delayed resuscitation with cardiopulmonary bypass (CPB), but intact survival is limited by neuronal death associated with microglial proliferation and activation. Pharmacological modulation of microglia may improve outcome following CA. Systemic injection of liposome-encapsulated clodronate (LEC) depletes macrophages. To test the hypothesis that intrahippocampal injection of LEC would attenuate local microglial proliferation after CA in rats, we administered LEC or PBS into the right or left hippocampus, respectively. After rapid exsanguination and 6min no-flow, hypothermia was induced by ice-cold (IC) or room-temperature (RT) flush. Total duration of CA was 20min. Pre-treatment (IC, RTpre) and post-treatment (RTpost) groups were studied, along with shams (cannulation only) and CPB controls. On day 7, shams and CPB groups showed neither neuronal death nor microglial activation. In contrast, the number of microglia in hippocampus in each individual group (IC, RTpre, RTpost) was decreased with LEC vs. PBS by ∼34-46% (P<0.05). Microglial proliferation was attenuated in the IC vs. RT groups (P<0.05). Neuronal death did not differ between hemispheres or IC vs. RT groups. Thus, intrahippocampal injection of LEC attenuated microglial proliferation by ∼40%, but did not alter neuronal death. This suggests that microglia may not play a pivotal role in mediating neuronal death in prolonged hypothermic CA. This novel strategy provides us with a tool to study the specific effects of microglia in hypothermic CA.


Sequences of cDNAs and expression of genes encoding chitin synthase and chitinase in the midgut of Spodoptera frugiperda.
The focus of this study was on the characterization and expression of genes encoding enzymes responsible for the synthesis and degradation of chitin, chitin synthase (SfCHSB) and chitinase (SfCHI), respectively, in the midgut of the fall armyworm, Spodoptera frugiperda. Sequences of cDNAs for SfCHSB and SfCHI were determined by amplification of overlapping PCR fragments and the expression patterns of these two genes were analyzed during insect development by RT-PCR. SfCHSB encodes a protein of 1523 amino acids containing several transmembrane segments, whereas SfCHI encodes a protein of 555 amino acids composed of a catalytic domain, a linker region and a chitin-binding domain. SfCHSB is expressed in the midgut during the feeding stages, whereas SfCHI is expressed during the wandering and pupal stages. Both genes are expressed along the whole midgut. Chitin staining revealed that this polysaccharide is present in the peritrophic membrane (PM) only when SfCHSB is expressed. There is little or no chitin in the midgut when SfCHI is expressed. These results support the hypothesis that SfCHSB is responsible for PM chitin synthesis during the larval feeding stages and SfCHI carries out PM chitin degradation during larval-pupal molting, suggesting mutually exclusive temporal patterns of expression of these genes.


Black hairy tongue after alprazolam intake.
A 31-year-old female with a diagnosis of bipolar disorder developed black hairy tongue after alprazolam therapy. Her symptom resolved 10 days after the cessation of alprazolam. Alprazolam is a widely used antidepressant and antianxiety drug. Mild to moderate side effect of alprazolam was commonly seen, including lethargy, dizziness, headache, dry mouth, nausea, fatigue, constipation, and blurred vision. In this case, we reported a patient developed black hairy tongue after alprazolam intake, and her symptom resolved after 10-day discontinuation of alprazolam. This rare adverse event should be of concern to clinicians. This is the first paper to report an alprazolam-induced BHT. This rare side effect of alprazolam should be concern of clinicians; we hope our report will promote the understand of BHT and acknowledge clinicians of this rare side effect of alprazolam.


A clinico-pathological approach to the classification of human demodicosis.
Demodicosis is a parasitic skin disease caused by the follicle mites Demodex folliculorum and Demodex brevis. Although there are several clinical variants of this disease, a clear classification is missing. To characterize the clinical features and course of the different forms of demodicosis. Prospective study of 87 patients with clinical symptoms of demodicosis and positive acarological findings. Each patient was examined an average of six times during the treatment period. We suggest that demodicosis be divided into both primary and secondary types. The usual etiological agent of primary demodicosis is D. folliculorum, which causes an erythemato-squamous eruption in the facial T-zone. The rash starts on unaltered skin and covers 8 - 15 % of the face. Pruritus accompanies the onset of the rash, while erythema is first apparent after papulo-pustules are seen and disappears after treatment. Half the patients show seasonal exacerbations. Secondary demodicosis is usually caused by D. brevis and characterized by a symmetrical malar papulo-pustular eruption. It develops on diseased skin and covers 30 - 40 % of the face. Pruritus starts after the lesion exacerbation, but erythema precedes the papulo-pustular phase and persists after treatment. Most patients flare during the summer. The facial distribution, seasonality and pathogenesis, as well as the species of mite involved, must be taken into consideration in separating the various forms of demodicosis.


Anesthesia inhibits poly I:C induced stimulation of natural killer cell cytotoxicity in mice.
The effects of general anesthesia on the levels of baseline and inducible splenic natural killer (NK) activity of mice were examined. General anesthesia significantly inhibited the induction of NK activity by Poly I:C, while having no effect on baseline NK. Since this effect was reproduced using three different anesthetics (Avertin, ether, and Ketamine/Xylazan), the inhibition of inducible NK activity is probably due to the state of general anesthesia, rather than to the pharmacological properties of the anesthetics. Inhibition of the Poly I:C mediated induction of NK was observed for at least 4 days after anesthesia. In contrast to anesthesia alone, anesthesia with surgery significantly decreased baseline NK activity. However, the addition of surgery to anesthesia did not significantly alter the level of inhibition of NK stimulation by Poly I:C compared to anesthesia treatment alone. Experiments assessing the NK modulatory effects of surgery alone were not performed. Interestingly, neither anesthesia alone nor anesthesia with surgery were able to significantly decrease splenic NK activity that had been induced with Poly I:C prior to anesthesia. In view of the important role of NK cells in the innate immune defenses, the possible clinical applications of these results are discussed.


Enhancement of CD4+ T-cell help reverses the doxorubicin-induced suppression of antigen-specific immune responses in vaccinated mice.
Multimodality treatments that combine conventional cancer therapies with antigen-specific immunotherapy have emerged as promising approaches for the control of cancer. In the current study, we have explored the effect of doxorubicin on the antigen-specific immune responses generated in mice vaccinated with calreticulin (CRT)/E6 and/or Ii-PADRE DNA. We observed that pretreatment with doxorubicin suppressed the E6-specific CD8+ T-cell immune responses generated by CRT/E6 DNA vaccination in vaccinated mice. In contrast, pretreatment with doxorubicin enhanced the PADRE-specific CD4+ T-cell immune responses generated by Ii-PADRE DNA vaccination. Furthermore, coadministration of Ii-PADRE DNA could not only reverse the suppression, but also enhanced the E6-specific CD8+ T-cell responses in CRT/E6-vaccinated mice pretreated with doxorubicin. Finally, treatment with doxorubicin followed by CRT/E6 combined with Ii-PADRE DNA vaccination led to enhanced antitumor effects and prolonged survival in TC-1 tumor-bearing mice. The clinical implications of the current study are discussed.


Individual and contextual factors associated with verbal bullying among Brazilian adolescents.
Few studies have been carried out in low- middle-income countries assessing contextual characteristics associated with bullying. This study aimed to assess the relative importance of contextual (school and city) and individual-level factors to explain the variance in verbal bullying among a nationally representative sample of Brazilian adolescents. 59,348 students from 1,453 schools and 26 state capitals and the Federal District participated in the National Survey of School Health among 9th Grade Students (PeNSE, 2009). We performed multilevel logistic regression in a three level model (individual, school and city). The 30-day prevalence of verbal bullying among these students was 14.2%. We found that 1.8% and 0.3% of the total variance in bullying occurred at school-level and city-level, respectively, and 97.9% at individual-level. At city-level, all factors included failed to demonstrate a significant association with bullying (p < 0.05) whereas at school-level, private schools presented more bullying than public schools (OR = 1.17, CI 1.04-1.31). At individual-level, male gender, younger age, not living with both parents, exposed to domestic violence, under or overweight were all associated with bullying. All socioeconomic indicators assessed contributed little to explain the variance in bullying at individual, school or city-level. Population subgroups at risk identified according to their individual profile could be targeted in future interventions in Brazil.


[Bronchoalveolar lavage in patients surgically treated with extracorporeal surgery].
Nineteen selected patients were operated of coronary artery bypass surgery or aortic valvular replacement. In this cohort a bronchoalveolar lavage was performed before and after cardiopulmonary bypass. A rise in the polimorphonuclear neutrophils count was found in the post-bypass lavage group. The increase on secuestration of neutrophils by the lung could be a manifestation of lung injury due to the cardiopulmonary bypass. A review of this topic is presented.


Involvement of intraterminal dopamine compartments in the amine release in the cat striatum.
A push-pull superfusion technique has been used in the anesthetized cat to study the simultaneous release of tritiated and total dopamine (DA) during continuous labelling with tritiated tyrosine. The concentration of tritiated and total DA (1.3 and 70 nM respectively) and dihydroxyphenylacetic acid (1 microM) have been measured in the extracellular space under our experimental conditions. The specific activity of spontaneously released DA was found to be 0.76 Ci/mmol. The release of tritiated and total amine following 3 h superfusion with [3H]tyrosine did not occur in parallel in response to the local application of either alpha-methyl-p-tyrosine (0.1 mM) or amphetamine (1 microM). Amphetamine induced an increase followed by a decrease in the specific activity of released DA which reflects an initial release of newly synthesized DA followed by the release of stored amine. The transfer between intraterminal pools of the amine is thus clearly evidenced. The results show that the simultaneous determination of tritiated and total DA release allows the relative contribution of the two intraterminal pools to the amine release to be monitored.


Surgical anatomy of hand allotransplantation.
The hand is the most refined anatomical terminal device known and the leading edge of the sensorium. Further, the hand is second only to the face in terms of visibility and is a vitally important aspect aesthetic and body image. Hand amputation represents a devastating loss of function and independence. Restoring function after limb loss is a challenge and traditionally includes autologous methods and prosthetics. In the last 15 years, hand transplantation has become a viable option for select patients.


Arthroscopic Superior Capsular Reconstruction Using "Sandwich" Patch Technique for Irreparable Rotator Cuff Tears.
The technique of superior capsular reconstruction (SCR) using fascia lata autograft, described by Mihata et al. in 2012, has been an acceptable and effective method for treating irreparable massive rotator cuff tears, especially in cases with severe fatty infiltration and tendon retraction. After the SCR procedure of Mihata et al., it was found that some graft failure occurred with thinning and elongation during the follow-up time, which was called graft "creep." To avoid graft creep and reduce graft failure rates after SCR, we created an arthroscopic SCR technique with a "sandwich" patch augmented with polyethylene terephthalate scaffold interspaced between 2 folded layers of fascia lata autograft.


Proteome data of Anopheles stephensi ovary using high-resolution mass spectrometry.
This article contains data on the proteins expressed in the ovaries of Anopheles stephensi, a major vector of malaria in India. Data acquisition was performed using a high-resolution Orbitrap-Velos mass spectrometer. The acquired MS/MS data was searched against An. stephensi protein database comprising of 11,789 sequences. Overall, 4407 proteins were identified, functional analysis was performed for the identified proteins and a protein-protein interaction map predicted. The data provided here is also related to a published article - "Integrating transcriptomics and proteomics data for accurate assembly and annotation of genomes" (Prasad et al., 2017) [1].


Irregular Bone Defect Repair Using Tissue-Engineered Periosteum in a Rabbit Model.
In previous studies, we succeeded in repairing a long bone defect with tissue-engineered periosteum (TEP), fabricated by incorporating rabbit mesenchymal stem cells with small intestinal submucosa. In this study, we investigated the feasibility of allogeneic irregular bone defect repair using TEP. We performed a subtotal resection of the scapula in 36 rabbits to establish a large irregular bone defect model. The rabbits were then randomly divided into three groups (n = 12 per group) and the defects were treated with TEP (Group 1), allogeneic deproteinized bone (DPB) (Group 2) or a hybrid of TEP and DPB (Group 3). At 4, 8, and 12 weeks after surgery, the rabbits were sacrificed, and the implants were harvested. X-ray radiographic and histological examinations were performed to detect bone healing. Ink-formaldehyde perfusion was introduced to qualitatively analyze vascularization in TEP engineered new bone. The repair of scapular defects was diverse in all groups, shown by radiographic and histological tests. The radiographic scores in Group 1 and Group 3 were significantly higher than Group 2 at 8 and 12 weeks (p < 0.05). Histological scores further proved that Group 1 had significantly greater new bone formation compared to Group 3 (p < 0.05), while Group 2 had the lowest osteogenesis at all time-points (p < 0.001). Ink-formaldehyde perfusion revealed aboundant microvessels in TEP engineered new bone. We conclude that TEP is promising for the repair of large irregular bone defects. As a 3D scaffold, DPB could provide mechanical support and a shaping guide when combined with TEP. TEP engineered new bone has aboundant microvessels.


Comparing treatment policies with assistance from the structural nested mean model.
Treatment policies, also known as dynamic treatment regimes, are sequences of decision rules that link the observed patient history with treatment recommendations. Multiple, plausible, treatment policies are frequently constructed by researchers using expert opinion, theories, and reviews of the literature. Often these different policies represent competing approaches to managing an illness. Here, we develop an "assisted estimator" that can be used to compare the mean outcome of competing treatment policies. The term "assisted" refers to the fact estimators from the Structural Nested Mean Model, a parametric model for the causal effect of treatment at each time point, are used in the process of estimating the mean outcome. This work is motivated by our work on comparing the mean outcome of two competing treatment policies using data from the ExTENd study in alcohol dependence.


Both near ultraviolet radiation and the oxidizing agent hydrogen peroxide induce a 32-kDa stress protein in normal human skin fibroblasts.
We have analyzed the pattern of protein synthesis in solar near ultraviolet (334 nm, 365 nm) and near visible (405 nm) irradiated normal human skin fibroblasts. Two hours after irradiation we find that one major stress protein of approximately 32 kDa is induced in irradiated cells. This protein is not induced by ultraviolet radiation at wavelengths shorter than 334 nm and is not inducible by heat shock treatment of these cells. Although sodium arsenite, diamide, and menadione all induced a 32-kDa protein, they also induced the major heat shock proteins. In contrast, the oxidizing agent, hydrogen peroxide, induced the low molecular weight stress protein without causing induction of the major heat shock proteins. A comparison of the 32-kDa proteins induced by sodium arsenite, H2O2, and solar near ultraviolet radiation using chemical peptide mapping shows that they are closely related. These results imply that the pathways for induction of the heat shock response and the 32-kDa protein are not identical and suggest that, at least in the case of radiation and treatment with H2O2, the 32-kDa protein might be induced in response to cellular oxidative stress. This conclusion is supported by the observation that depletion of endogenous cellular glutathione prior to solar near ultraviolet irradiation lowers the fluence threshold for induction of the 32-kDa stress protein.


The effects of dynamic changes of malonyl ginsenosides on evaluation and quality control of Panax ginseng C.A. Meyer.
To clarify the effects of malonyl ginsenosides (MGR) on evaluation and quality control of Panax ginseng, the contents of neutral and malonyl ginsenosides from P. ginseng were examined by high-performance liquid chromatography equipped with UV-VIS detector (HPLC-UV) during extraction, processing and storage. Several solvents, including water, ethanol, methanol, and n-butanol were used in the cold-soaked extraction (CSE). Among the four extraction solvents, methanol was found to be the most efficient. CSE was compared with other extraction methods such as Soxhlet extraction (SE), heat reflux extraction (HRE), ultrasonic-assisted extraction (UAE), and microwave-assisted extraction (MAE). The content of MGR showed significant differences, higher in CSE and UAE; lower in MAE and HRE; no MGR could be detected after SE. However, the total contents of neutral and malonyl ginsenosides were not different. Meanwhile, white ginseng, stored at 25°C in air of low humidity, showed a marked decrease in the concentration of MGR from 1.19% to 0.63% but with an increase in the neutral ginsenosides from 1.12% to 1.53% after 0-9-month storage. The results indicated that MGR changed dynamically in P. ginseng with different extraction solvents, extraction methods and increasing storage time. The total ginsenosides was not only underestimated but also determined imprecisely by ignoring malonyl ginsenosides. On the basis of our results, we suggest that malonyl ginsenosides should be transformed into the corresponding neutral ginsenosides during sample preparation for quality control and evaluation of P. ginseng. Then the content of six neutral ginsenosides in samples was used as the true level of total ginsenosides. The results reported here might provide useful information for accurate evaluation and quality control of P. ginseng.


Alveolar soft-part sarcoma of the tongue. Report of a case.
A case of alveolar soft-part sarcoma (ASPS) of the tongue in a 19-year-old boy is presented. He underwent a hemiglossectomy and received chemotherapy and has been free of disease for 3 years. The origin of intracytoplasmic periodic acid-Shiff(PAS)-positive crystals found in the tumor and the histogenesis of ASPS are briefly discussed.


Immersion A-scan compared with partial coherence interferometry: outcomes analysis.
To compare 2 methods of axial length measurement, immersion ultrasonography and partial coherence interferometry, and to elucidate surgical outcomes based on immersion measurements. Oregon Eye Institute, Eugene, Oregon, USA. Axial length measurements in 50 cataractous eyes were obtained by optical biometry (IOLMaster, Zeiss Humphrey Systems) and immersion ultrasound (Axis II, Quantel Medical), and the results were compared. Intraocular lens (IOL) power calculations in the same eyes after cataract extraction and posterior chamber IOL implantation were evaluated retrospectively based on the postoperative spherical equivalent prediction error. Immersion ultrasonography and partial coherence interferometry measurements correlated in a highly positive manner (correlation coefficient = 0.996). Outcomes analysis demonstrated 92.0% of eyes were within +/-0.5 diopter of emmetropia based on immersion axial length measurements. Immersion ultrasonography provided highly accurate axial length measurements and permitted highly accurate IOL power calculations.


Coronavirus Disease 2019 and Hypertension: How Anti-hypertensive Drugs Affect COVID-19 Medications and Vice Versa.
As a medical problem, hypertension is one of the most common disorders in cardiovascular disease. High blood pressure has been identified as one of the most familiar risk factors for the ongoing COVID-19 pandemic. We planned to explore the possible interactions between anti-hypertensive agents and drugs targeting SARS-CoV-2 with broad investigations of these medications' mechanism of action and adverse effects. Two co-authors searched the electronic databases (PubMed, Scopus, and Google Scholar) to collect papers relevant to the subject. The keywords searched were angiotensin-converting enzyme inhibitors (ACEI), angiotensin-II receptor blockers (ARBs), sympatholytic drugs (alpha-1 blockers, beta-blockers), vasodilators (calcium channel blockers, nitrates, and hydralazine), diuretics, chloroquine, hydroxychloroquine, lopinavir/ritonavir, remdesivir, favipiravir, interferons, azithromycin, anti-cytokine agents, glucocorticoids, anticoagulant agents, nitric oxide, and epoprostenol. QT prolongation, arrhythmia, hypokalemia, hypertriglyceridemia are the most dangerous adverse effects in the patients on COVID-19 medications and anti-hypertensive drugs. This review emphasized the importance of the potential interaction between drugs used against COVID-19 and anti-hypertensive agents. Therefore, caution must be exercised when these medications are being used simultaneously.


Imaging of the renal donor and transplant recipient.
Renal transplant remains the mainstay of the treatment of end-stage renal disease. With improvement in management strategies and the diverse imaging options, the yearly survival of recipients with functional kidneys has improved significantly. This improved survival is attributed to factors such as immunosuppressive therapy planning in recipients, human leukocyte antigen matching, surgeon experience, and recipient's age. Transplantation offers the closest thing to a normal state if the transplanted kidney can replace the failed kidneys. Living-donor kidney transplants are playing a vital role in bridging the gap between decreased supply of, and increased demand for, kidneys for transplant. Early detection and characterization of complications in the recipient are of immense clinical relevance, allowing timely intervention to prevent graft failure.


Evaluation of the ulnopalmar arterial arches with pulse oximetry and plethysmography: comparison with the Allen's test in 1010 patients.
To avoid ischemic hand complications, the percutaneous transradial approach is only performed in patients with patent hand collateral arteries, which is usually evaluated with the modified Allen's test (MAT). This qualitative test measures the time needed for maximal palmar blush after release of the ulnar artery compression with occlusive pressure of the radial artery. The objectives were to evaluate the patency of the hand collateral arteries and to compare MAT with combined plethysmography (PL) and pulse oximetry (OX) tests before the percutaneous transradial approach. Patients referred to the catheterization laboratory were prospectively examined with MAT, PL, and OX tests. PL readings during radial artery compression were divided into 4 types: A, no damping; B, slight damping of pulse tracing; C, loss followed by recovery; or D, no recovery of pulse tracing within 2 minutes. OX results were either positive or negative. Results of both tests were compared in 1010 consecutive patients. MAT results < or =9 seconds on either hand were seen in 93.7% of patients. PL and OX types A, B, or C on either hand were seen in 98.5% of patients. On the basis of the MAT < or =9 seconds criteria, 6.3% of patients were excluded from the transradial approach, whereas with PL and OX types A, B, and C, only 1.5% of patients were excluded. There was more exclusion in men and with increasing age by using both methods. In the evaluation of hand collaterals, PL and OX were found to be more sensitive than MAT. When applied to transradial approach screening, only 1.5% of patients were not suitable candidates for the transradial approach.


Occurrence and reproducibility of the "skip" phenomenon in bactericidal testing of Staphylococcus aureus.
A "skip" phenomenon, in which subcultures to determine bactericidal endpoints show discordant results, can make bactericidal testing of Staphylococcus aureus difficult to interpret. Either a single or several consecutive concentrations may be skipped, with insignificant growth from these concentrations, but heavy growth from higher antimicrobic concentrations. Replicate macrodilution minimum bactericidal concentration testing of cephalothin against S. aureus was investigated to determine the frequency and reproducibility of the skip phenomenon in this test. In preliminary testing, the skip phenomenon occurred at 24 hr in 11 of the 30 tests performed on ten S. aureus strains. Incubation of tubes for 48 hr before subculture markedly reduced the number of tests containing a skip tube (four of 30). The skip phenomenon was not reproducible either within concurrent replicate testing or on repeat testing of the same isolate on subsequent days. The ten strains were retested in replicative trials using the macrodilution test comparing Mueller-Hinton broth (MHB) and MHB supplemented with Tween 80. The number of skips occurring in the supplemented broth test was the same (two of 22) at 24 hr as nonsupplemented broth. For reproducible results, macrodilution minimum bactericidal testing requires performance of the test in duplicate, with repeat subculture at 48 hr if the skip phenomenon occurs in both trials at the 24-hr subculture. Killing curves performed on these isolates did not appear to demonstrate any relationship between the skip phenomenon and the paradoxical effect described by Eagle.


Relationship between bone resorption, oxidative stress and inflammation in severe COPD exacerbation.
The natural course of chronic obstructive pulmonary disease (COPD) is complicated by the development of systemic consequences and co-morbidities. Increasing evidence indicates that COPD and osteoporosis are strongly linked. The common features in COPD pathology, history of smoking, age, inactivity, systemic inflammation, and use of systemic corticosteroids, are important risk factors for osteoporosis. Pulmonary function, matrix metalloproteinase, tissue inhibitor of metalloproteinases, oxidative stress parameters, inflammatory markers and bone resorption marker were measured in 85 COPD patients and 47 healthy subjects. In patients, all parameters were assessed at two time points: one day after admission during exacerbation and about 30 days after, in the stable state of disease. In patients, bone resorption marker collagen type I β-isomerized C-terminal telopeptide (beta CL) was increased during exacerbation: geometric mean 0.521, compared with stable patients 0.408, p<0.01, and control subjects 0.362 ng/ml, p<0.001. During exacerbation high sensitivity C-reactive protein (hsCRP) and neutrophil count were significantly higher in COPD patients compared with the control group, p<0.001. Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations were significantly higher in COPD patients, stable state or exacerbation, compared with control subjects, p<0.001. In patients during exacerbation, total oxidative status (TOS) was higher compared with the stable state, p<0.05 and control group, p<0.001. Multiple linear regression for the joint influence of inflammation, hypoxia and oxidative status during exacerbation showed almost 60% influence on the variability of beta CL concentrations. Intensification of disease characteristic symptoms such as inflammation, hypoxia, protease/antiprotease imbalance and oxidative stress, during exacerbation episodes in COPD patients may also contribute to increased bone resorption.


Study of the positivity of spontaneous and directed diagnosis of leukoaraiosis in the elderly by cranial computerized tomography, and its correlation with cognitive deficit and cardiovascular risk factors.
To evaluate the prevalence of leukoaraiosis (LA) and its correlation with vascular risk factors and the cognitive performance of elderly patients. 78 patients were randomly selected and submitted to clinic-laboratorial evaluation for vascular risk factors. Two cognitive tests were performed. All patients were submitted to cranial computerized tomography (CT), which was analyzed in two situations: the spontaneous and the directed way. There was no statistically significant difference between the prevalence of spontaneous and the directed diagnoses of LA (20.5 and 18%, respectively). The presence of LA was not significantly correlated with cognitive impairment. Only age was positively associated with LA. Cranial CT is a trustworthy method for the diagnosis of LA. Only age showed a positive association. No clinical implications were found, concerning the cognitive performance of the patients.