Biochemical analysis of decreased ornithine transport activity in the liver mitochondria from patients with hyperornithinemia, hyperammonemia and homocitrullinuria.
Hyperornithinemia, hyperammonemia and homocitrullinuria (HHH disorder) is an inherited metabolic disorder which shows peculiar amino acid changes in the serum and urine. The primary defect is considered to be the transport of ornithine across the mitochondrial membrane, but there is no direct evidence for this so far. We have analyzed ornithine transport activities in the liver mitochondria from three patients with HHH disorder. In coupled liver mitochondria we demonstrated low activities of citrulline synthesis and low rates of ornithine uptake. However, there were no abnormalities in carbamoyl-phosphate synthetase activity, ornithine carbamoyltransferase activity, N-acetylglutamate levels or O2 uptake with succinate. We also performed a kinetic study of citrulline synthesis as a function of ornithine concentration. We found increased Km values for ornithine and varied Vmax values of citrulline synthesis, which suggested the presence of a mutant transport protein. From these results we conclude that the defect of hyperornithinemia, hyperammonemia and homocitrullinuria lies in the transport of ornithine across the mitochondrial membrane.


The Dutch HEXACO Personality Inventory: psychometric properties, self-other agreement, and relations with psychopathy among low and high acquaintanceship dyads.
The HEXACO model (Lee & Ashton, 2004, 2006) of personality structure is based on 6 dimensions that have been recovered in lexical studies of personality in various languages. In this study, we examined a Dutch version of the HEXACO Personality Inventory (HEXACO-PI; Lee & Ashton, 2004) and found it to have satisfactory psychometric properties. Additionally, we examined the level of self-other agreement for the HEXACO-PI variables and the relation of HEXACO-PI Honesty-Humility with the Self-Report Psychopathy Scale (Williams, Paulhus, & Hare, 2007) at varying levels of self-other acquaintanceship. Self-other agreement was found to be high, especially among dyads with high levels of acquaintanceship. Self-reported and other-reported Honesty-Humility and Emotionality were the strongest predictors of psychopathy. The relation between other-reported Honesty-Humility and self-reported psychopathy was near zero for dyads with low levels of acquaintanceship but was moderately strong for dyads with high levels of acquaintanceship.


Assessment of the short-term functional outcome after urethroplasty: a prospective analysis.
To assess the short-term functional outcomes on urinary symptoms, erectile function, urinary continence and patient's satisfaction after urethroplasty. A prospective analysis was done in 21 patients who underwent urethroplasty. An assessment of the urinary flow, urinary symptoms (International Prostate Symptoms Score <IPSS>), erectile function (International Index of Erectile Function-5 <IIEF-5>) and urinary continence International Consultation Committee on Incontinence Questionnaire male Short Form <ICI-Q-SF>) was done before urethroplasty and 6 weeks and 6 months after urethroplasty. Patients were also asked to score their satisfaction with the urethroplasty after 6 weeks and 6 months. Mean patient's age was 48 years range: 26-80 years). Mean stricture length was 4.2 cm (range: 1-12 cm). Three patients suffered a stricture recurrence. Mean maximum urinary flow increased from 5.83 mL/s to 24.92 mL/s (p < 0.001). Mean IPSS preoperative, 6 weeks and 6 months postoperative was respectively 15.86, 4.60 and 6.41(p < 0.001). The mean IIEF-5 score preoperative, 6 weeks and 6 months postoperative was respectively 15, 12.13 and 11.62 (not significant). The mean ICI-Q-SF score preoperative, 6 weeks and 6 months postoperative was respectively 10.47, 8.33 (p = 0.04) and 9.47 (p = 0.31). Patient's satisfaction 6 weeks and 6 months postoperative was respectively 17.14/20 and 17.12/20. Urethroplasty leads to a significant improvement in urinary flow and IPSS and urinary continence is tending to improve. Although not significant, erectile function was slightly diminished after urethroplasty. Functional outcome should be assessed when urethroplasty is performed.


Hard-wired models of working memory and temporal sequence storage and generation.
We develop hard-wired simulations of temporal sequence storage and generation by multi-modular networks based on the frontal lobe system (cortex, basal ganglia and thalamus). Single cell activity is shown to have been constructed so as to mimic results measured in monkeys on a similar task, indicating that a suitable form of chunking had been achieved in the models. The mathematical nature of these processes is discussed, from the viewpoint of bifurcation theory.


metaSpectraST: an unsupervised and database-independent analysis workflow for metaproteomic MS/MS data using spectrum clustering.
The high diversity and complexity of the microbial community make it a formidable challenge to identify and quantify the large number of proteins expressed in the community. Conventional metaproteomics approaches largely rely on accurate identification of the MS/MS spectra to their corresponding short peptides in the digested samples, followed by protein inference and subsequent taxonomic and functional analysis of the detected proteins. These approaches are dependent on the availability of protein sequence databases derived either from sample-specific metagenomic data or from public repositories. Due to the incompleteness and imperfections of these protein sequence databases, and the preponderance of homologous proteins expressed by different bacterial species in the community, this computational process of peptide identification and protein inference is challenging and error-prone, which hinders the comparison of metaproteomes across multiple samples. We developed metaSpectraST, an unsupervised and database-independent metaproteomics workflow, which quantitatively profiles and compares metaproteomics samples by clustering experimentally observed MS/MS spectra based on their spectral similarity. We applied metaSpectraST to fecal samples collected from littermates of two different mother mice right after weaning. Quantitative proteome profiles of the microbial communities of different mice were obtained without any peptide-spectrum identification and used to evaluate the overall similarity between samples and highlight any differentiating markers. Compared to the conventional database-dependent metaproteomics analysis, metaSpectraST is more successful in classifying the samples and detecting the subtle microbiome changes of mouse gut microbiomes post-weaning. metaSpectraST could also be used as a tool to select the suitable biological replicates from samples with wide inter-individual variation. metaSpectraST enables rapid profiling of metaproteomic samples quantitatively, without the need for constructing the protein sequence database or identification of the MS/MS spectra. It maximally preserves information contained in the experimental MS/MS spectra by clustering all of them first and thus is able to better profile the complex microbial communities and highlight their functional changes, as compared with conventional approaches. tag the videobyte in this section as ESM4 Video Abstract.


Nursing student resilience: a concept clarification.
The purpose of this article is to clarify the concept of resilience for the nursing student population. A selective review of the literature was conducted, with 26 sources found to be cogent to this concept clarification, including four recently published concept analyses. The Norris method of concept clarification is used to analyze and clarify the concept of resilience to enhance its practical application. The phenomenon is described according to its antecedents, attributes, and consequences, along with a proposed operational definition and conceptual model. The clarification of the concept will assist nurse researchers and nurse educators in developing interventions and educational strategies aimed at fostering resilience in nursing students.


Deficiency of pseudogene UPAT leads to hepatocellular carcinoma progression and forms a positive feedback loop with ZEB1.
Hepatocellular carcinoma (HCC) is a common disease worldwide. Accumulating reports have evidenced the internal connection between epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs), as well as their significance in metastasis and post-operative recurrence. In this study, we investigated an interesting ubiquitin-proteasome pathway associated pseudogene of AOC4, also known as UPAT, and showed that it was downregulated in 39.78% (37/93) of patients with hepatitis B virus (HBV)-related HCC. Downregulation of UPAT was associated with multiple worse clinicopathological parameters, as well as decreased recurrence-free survival (RFS). In vitro and in vivo assays found that overexpression of UPAT significantly suppressed cellular migration, invasion, EMT processes, and CSC properties. Mechanistic studies showed that UPAT promoted ZEB1 degradation via a ubiquitin-proteasome pathway and, in contrast, ZEB1 transcriptionally suppressed UPAT by binding to multiple E-box (CACCTG) elements in the promoter region. Moreover, UPAT was negatively correlated with ZEB1 protein in HCC tissues, their combined expression discriminated RFS outcomes for patients with HBV-related HCC. These data on the UPAT-ZEB1 circuit-mediated pathway will further knowledge on EMT and CSCs, and may help to develop novel therapeutic approaches for the prevention of HCC metastasis.


Whole Grain and Refined Grains: An Examination of US Household Grocery Store Purchases.
The health benefits related to intake of whole grain foods are well established. Consumption of whole grains in the US population is low, and whole grain content can vary greatly depending upon the specific products that are purchased. To examine the proportion of products purchased by US households containing whole grain and refined grain ingredients using time-specific food composition data, and examine whether purchases differ between income, race or ethnicity, and household make-up. Nationally representative Nielsen Homescan 2018 data were used. Each barcoded product captured in Nielsen Homescan 2018 was linked with ingredient information using commercial nutrition databases in a time-relevant manner. Packaged food products containing whole grain ingredients, refined grain ingredients, neither, or both were identified. The percentage of packaged food products containing whole grain and refined grain ingredients purchased by US households was determined overall, by demographic subgroup, and by food category. The proportion of packaged food purchases containing refined grain ingredients was significantly higher than whole grain ingredients (30.9% compared with 7.9%; P < 0.0001). Lower income households and households with children purchased a significantly higher proportion of products containing refined grain ingredients, with no nutritionally meaningful racial or ethnic differences observed. Concerningly, across all demographic subgroups >90% of bread purchases contained refined grain ingredients, and the 5 categories with the largest proportion of whole grain ingredients contributed to <20% of overall US household packaged food purchases. US households are purchasing a significantly higher proportion of packaged food products containing refined grain ingredients than whole grain ingredients. Future policy changes are needed to provide incentives and information (e.g., front-of-pack labels) to aid in encouraging manufacturers to increase whole grain product offerings while decreasing refined grain offerings, and to encourage consumers to substitute away from refined grain products toward whole grain products.


MR urography findings of a duplicated ectopic ureter in an adult man.
In this report we present the imaging findings in an adult male with a duplicated ectopic ureter which inserted into the prostatic urethra. The appearances at excretory urography, US, CT, and MR urography are described together with the potential pitfalls of the imaging techniques. Both US and MR urography accurately image the collecting system from the kidney to the point of distal ureteral insertion, and in our patient, MR urography provided similar information to US.


Influence of tourism, governance, and foreign direct investment on energy consumption and CO2 emissions: a panel analysis of Muslim countries.
The empirical linkages from tourism, governance, and FDI have been quantified on CO2 emission and energy use over 2002-2014 for a panel of 13 Muslim countries. To this end, we have examined the data for cross-sectional dependence (CD) and panel heterogeneity and employed panel algorithms, which account for both CD and panel heterogeneity. The results from Pedroni, Westerlund, and Kao tests supported the existence of a cointegration association between the chosen variables. In the CO2 model, we observed that tourism positively, and governance negatively, influences the CO2 emission. However, in the case of the energy model, the results of tourism pose a negative relationship, and governance indicates a positive relationship with energy use. The results supported the pollution haven phenomenon, finance, and energy triggered pollution in the study area. Further, the research supported a two-way causality between tourism and CO2, where there is a unilateral causality from governance to CO2. Similarly, a unidirectional causality was obtained from energy towards tourism. Lastly, the key policy recommendations based on the outcomes of the study are encouraging clean energy investment, enhancing good governance, and sustainable tourism development for improving environmental quality.


Family aspects, physical fitness, and physical activity associated with mental-health indicators in adolescents.
The objective of the study was to analyze the associations of family aspects, physical fitness, and physical activity with mental-health indicators in a sample of adolescents from Colombia. A cross-sectional study carried out in a sample of 988 adolescents (11-17 years-old) from public schools in Montería. Mental-health indicators were evaluated: Stress, depression, anxiety, happiness, health-related quality of life (HRQL), and subjective wellness. Family aspects included family affluence, functionality, and structure. These variables, along with physical activity and screen time, were measured with questionnaires. A fitness score was established by assessing the components of fitness: Flexibility, cardiorespiratory fitness, grip strength, and lower-limb strength. Associations were analyzed by multivariate linear regression models. Nuclear family structure was associated with lower stress level (- 1.08, CI: - 1.98 - -0.18), and family functionality was associated with all the studied mental-health indicators (Stress: -0.11, CI: - 0.17 - -0.06; depression: -0.20, CI: - 0.25 - -0.16; trait anxiety: -0.13, CI: - 0.18 - -0.09; state anxiety: -0.12, CI: - 0.17 - -0.08; happiness: 0.09, CI: 0.07 - 0.1; HRQL: 1.13, CI: 0.99 - 1.27; subjective wellness: 1.67, CI: 1.39 - 1.95). Physical activity was associated (β, 95% Confidence Interval (CI)) with depression (- 0.27, - 0.57 - -0.02), trait anxiety (- 0.39, CI: - 0.65 - -0.13), state anxiety (- 0.30, CI: - 0.53 - -0.07), happiness (0.14, CI: 0.06 - 0.22), HRQL (3.63, CI: 2.86 - 4.43), and subjective wellness (5.29, CI: 3.75 - 6.83). Physical fitness was associated with stress (- 0.80, CI: - 1.17 - -0.43), state anxiety (- 0.45, CI: - 0.73 - -0.17), and HRQL (1.75, CI: 0.82 - 2.69); screen time was only associated with stress (0.06, CI: 0.02 - 0.11). Family aspects were associated with mental health indicators, especially family functionality which was associated all mental-health indicators. Similarly, fitness, physical activity, and screen time were associated with the studied indicators of mental health. Particularly, physical activity was associated with all the mental-health indicators, except stress, which was only associated with screen time. Physical fitness was associated with stress, anxiety, and HRQL. Future studies could explore the causal relationships of fitness, physical activity and screen time with mental health in adolescents.


Molecular mechanics calculations on deaminooxytocin and on deamino-arginine-vasopressin and its analogues.
The backbone conformations of the cyclic moieties of 1-[beta-mercaptopropionic acid]-oxytocin [( Mpa1]-OT), [1-beta-mercaptopropionic acid]-arginine-vasopressin [( Mpa1]-AVP), [1-(beta'-mercapto-beta,beta-cyclopentamethylene)propionic acid]-arginine-vasopressin [( Cpp1]-AVP), and [1-thiosalicylic acid]-arginine-vasopressin [( Ths1]-AVP) have been analyzed by means of molecular mechanics. In these calculations, the side chains were simulated by pseudoatoms. For the three last compounds, the calculations were also performed on the whole molecules, in order to shed light on the differences in their biological activity. Their starting conformations were obtained by attaching the acyclic tail and side chains to the lowest energy conformations of the cyclic parts. In the case of [Ths1]-AVP, however, other starting conformations were also examined, which were obtained by attaching the planar benzene ring to the lowest energy conformations of [Mpa1]-AVP. In the calculations, all the degrees of freedom were relaxed and Weiner's force field was used, the parameters required for the benzene parts of [Ths1]-AVP being determined from the experimental data available, as well as from the results of molecular dynamics calculations on the model compounds. The lowest energy conformations of [Mpa1]-AVP and [Cpp1]-AVP are similar, while [Ths1]-AVP differs from them near the disulphide region, due to the presence of a planar benzene ring. Interactions involving the charged guanidine group of arginine make, in each case, an important contribution to the conformational energy. A model description of the shapes of the oxytocin and vasopressin ring has been proposed, which is based on the cyclohexane geometry. This description is in good correlation with the energetics of the conformations corresponding to different shapes.


Beyond Gender Identity Disorder Diagnoses Codes: An Examination of Additional Methods to Identify Transgender Individuals in Administrative Databases.
Large administrative databases often do not capture gender identity data, limiting researchers' ability to identify transgender people and complicating the study of this population. The objective of this study was to develop methods for identifying transgender people in a large, national dataset for insured adults. This was a retrospective analysis of administrative claims data. After using gender identity disorder (GID) diagnoses codes, the current method for identifying transgender people in administrative data, we used the following 2 strategies to improve the accuracy of identifying transgender people that involved: (1) Endocrine Disorder Not Otherwise Specified (Endo NOS) codes and a transgender-related procedure code; or (2) Receipt of sex hormones not associated with the sex recorded in the patient's chart (sex-discordant hormone therapy) and an Endo NOS code or transgender-related procedure code. Seventy-four million adults 18 years and above enrolled at some point in commercial or Medicare Advantage plans from 2006 through 2017. We identified 27,227 unique transgender people overall; 18,785 (69%) were identified using GID codes alone. Using Endo NOS with a transgender-related procedure code, and sex-discordant hormone therapy with either Endo NOS or transgender-related procedure code, we added 4391 (16%) and 4051 (15%) transgender people, respectively. Of the 27,227 transgender people in our cohort, 8694 (32%) were transmasculine, 3959 (15%) were transfeminine, and 14,574 (54%) could not be classified. In the absence of gender identity data, additional data elements beyond GID codes improves the identification of transgender people in large, administrative claims databases.


Characteristics, speciation, and bioavailability of mercury and methylmercury impacted by an abandoned coal gangue in southwestern China.
During coal mining activities, a lot of coal gangue is produced, which usually contains high mercury (Hg) concentrations as well as the acid mine drainage (AMD) generator of pyrite. In the present study, the total mercury (THg) and methylmercury (MeHg) in gangue, water, sediment, paddy soil, and rice samples, collected from abandoned coal mining areas, were analyzed. Results showed that the THg concentrations ranged from 0.37 to 35 mg/kg (11 ± 8.4 mg/kg) and 0.15 to 19 mg/kg (2.0 ± 3.9 mg/kg) in gangue and sediments, respectively. For paddy soils, the THg concentrations and MeHg varied from 0.16 to 0.91 mg/kg and 0.71 to 11 ng/g, respectively. Rice samples exhibited wide concentration ranges of THg (3.0-22 ng/g) and MeHg (0.71-8.9 ng/g). Sequential extraction of Hg revealed that the nitric acid-extractable state Hg (F4) was the dominant Hg species in gangue and sediment, while humic acids state Hg (F3) was the dominant form in paddy soil. Compared with gangue, higher percentages of F3 and the residual state Hg (F5) in both sediment and soil samples implied the transformation of F4 to F3 and F5 during transportation. Soil n-HAs (the difference between the total organic carbon and humic acids) were positively correlated with both THg and MeHg in soil and rice, indicating that n-HAs enhance Hg bioavailability under acidic conditions. Further studies should be conducted to reveal the factors influencing the transformation of different Hg fractions, providing ideas on decreasing the bioavailability of Hg in coal mining areas.


Erratum to: Peginterferon and Entecavir Combination Therapy Improves Outcome of Non-Early Response Hepatitis B e Antigen-Positive Patients.
[This corrects the article DOI: 10.1093/ofid/ofaa462.].


SAR of novel biarylmethylamine dopamine D4 receptor ligands.
SAR for a novel series of dopamine D4 receptor ligands is shown. Very selective, highly potent compounds like 1-(2-pyrimidinyl)-4-(3-(3-thienyl)-benzyl)-piperazine (5f) and 2-(4-(1-fluorenylmethyl)-1-piperazinyl)-pyrimidine (8c) were obtained.


Bayesian Probabilistic Projection of International Migration.
We propose a method for obtaining joint probabilistic projections of migration for all countries, broken down by age and sex. Joint trajectories for all countries are constrained to satisfy the requirement of zero global net migration. We evaluate our model using out-of-sample validation and compare point projections to the projected migration rates from a persistence model similar to the method used in the United Nations' World Population Prospects, and also to a state-of-the-art gravity model.


Kinesin-7 CENP-E regulates the formation and structural maintenance of the acrosome.
The acrosome is a special organelle that develops from the Golgi apparatus and the endolysosomal compartment in the spermatids. Centromere protein E (CENP-E) is an essential kinesin motor in chromosome congression and alignment. This study is aimed at investigating the roles and mechanisms of kinesin-7 CENP-E in the formation of the acrosome during spermatogenesis. Male ICR mice are injected with GSK923295 for long-term inhibition of CENP-E. Chemical inhibition and siRNA-mediated knockdown of CENP-E are carried out in the GC-2 spd cells. The morphology of the acrosomes is determined by the HE staining, immunofluorescence, and transmission electron microscopy. We have identified CENP-E is a key factor in the formation and structural maintenance of the acrosome during acrosome biogenesis. Long-term inhibition of CENP-E by GSK923295 results in the asymmetric acrosome and the dispersed acrosome. CENP-E depletion leads to the malformation of the Golgi complex and abnormal targeting of the PICK1- and PIST-positive Golgi-associated vesicles. Our findings uncover an essential role of CENP-E in membrane trafficking and structural organization of the acrosome in the spermatids during spermatogenesis. Our results shed light on the molecular mechanisms involved in vesicle trafficking and architecture maintenance of the acrosome.


Detection and quantitation of Solenopsis invicta virus-2 genomic and intermediary replicating viral RNA in fire ant workers and larvae.
Quantitative real-time PCR (QPCR) was used to quantify the genome of Solenopsis invicta virus-2 (SINV-2) from infected individual ants of S. invicta. Strand-specific cDNA synthesis oligonucleotide primers and RNase digestion after cDNA synthesis allowed quantification of plus (genomic) and minus (replicative) strands of the SINV-2 genome. Both strands were detected in adult workers and larval fire ants indicating that the virus was replicating within the ant. The differences between the genomic to replicative strand ranged from 199-fold in larvae to 479-fold in workers with an average ratio of 339:1.


Hypoconnectivity networks in schizophrenia patients: A voxel-wise meta-analysis of Rs-fMRI.
In recent years several meta-analyses regarding resting-state functional connectivity in patients with schizophrenia have been published. The authors have used different data analysis techniques: regional homogeneity, seed-based data analysis, independent component analysis, and amplitude of low frequencies. Hence, we aim to perform a meta-analysis to identify connectivity networks with different activation patterns between people diagnosed with schizophrenia and healthy controls using voxel-wise analysis. We collected primary studies exploring whole brain connectivity by functional magnetic resonance imaging at rest in patients with schizophrenia compared with healthy controls. We identified 25 studies included high-quality studies that included 1285 patients with schizophrenia and 1279 healthy controls. The results indicate hypoactivation in the right precentral gyrus and the left superior temporal gyrus of patients with schizophrenia compared with healthy controls. These regions have been linked with some clinical symptoms usually present in Plea with schizophrenia, such as auditory verbal hallucinations, formal thought disorder, and the comprehension and production of gestures.


Carotenoids, vitamin A, and their association with the metabolic syndrome: a systematic review and meta-analysis.
Modifiable factors that reduce the burden of the metabolic syndrome (MetS), particularly plant-derived biomarkers, have been a recent focus of rising interest. This systematic review and meta-analysis, which follows PRISMA guidelines, evaluates evidence from a period of 20 years that links vitamin A and carotenoids with the occurrence of MetS and following the PRISMA guidelines. PubMed and Cochrane databases (January 1997 through March 2017) were systematically assessed for studies, including case-control, cross-sectional, and cohort studies, that evaluated the associations of MetS with carotenoids and retinyl esters and retinol (vitamin A). Key measures of associations were harmonized into odds ratios (ORs) and 95% confidence intervals (95%CI) of MetS per 1 standard deviation (SD) of exposure using forest plots and random effects models that pooled data points from 11 cross-sectional studies. Begg's funnel and harvest plots were constructed. An inverse association between total carotenoids and MetS was found [ORpooled, 0.66; 95%CI, 0.56-0.78; 1 SD ∼ 0.82 µmol/L; n = 5 studies]. This association was the strongest for β-carotene, followed by α-carotene and β-crypotoxanthin. No association was detected between retinol and MetS (ORpooled, 1.00; 95%CI, 0.88-1.13; 1 SD ∼ 2.14 µmol/L; n = 6 studies). Publication bias was absent, and harvest plots indicated consistency upon replication for β-carotene and total carotenoid exposures. This review and meta-analysis suggests that, unlike retinol, total and individual carotenoids were inversely related to MetS.


Alerting attention and time perception in children.
This experiment investigated the effect of a signal (i.e., a click) warning of the arrival of a stimulus to be timed on temporal discrimination in children aged 3, 5, and 8 years (N=86), using a bisection task with visual stimuli ranging from 0.5 to 2s or 1 to 4s. In all groups, the psychophysical functions were orderly with the proportion of long responses increasing with the stimulus duration, although the steepness of functions increased with age. Stimulus durations were judged to be longer with than without the click in all age groups. With the click, time sensitivity also improved and more particularly in the younger children. The statistical results suggest, within the framework of the scalar timing theory, that the click reduces the closing latency of the switch that connects the pacemaker to the accumulator in the internal clock and also reduces its trial-by-trial variability.


Long-term effects on cancer survivors' quality of life of physical training versus physical training combined with cognitive-behavioral therapy: results from a randomized trial.
We compared the effect of a 12-week group-based multidisciplinary self-management rehabilitation program, combining physical training (twice weekly) and cognitive-behavioral therapy (once weekly) with the effect of 12-week group-based physical training (twice weekly) on cancer survivors' quality of life over a 1-year period. One hundred forty-seven survivors [48.8 +/- 10.9 years (mean +/- SD), all cancer types, medical treatment > or = 3 months ago] were randomly assigned to either physical training (PT, n = 71) or to physical training plus cognitive-behavioral therapy (PT + CBT, n = 76). Quality of life and physical activity levels were measured before and immediately after the intervention and at 3- and 9-month post-intervention using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 questionnaire and the Physical Activity Scale for the Elderly, respectively. Multilevel linear mixed-effects models revealed no differential pattern in change of quality of life and physical activity between PT and PT + CBT. In both PT and PT + CBT, quality of life and physical activity were significantly and clinically relevantly improved immediately following the intervention and also at 3- and 9-month post-intervention compared to pre-intervention (p < 0.001). Self-management physical training had substantial and durable positive effects on cancer survivors' quality of life. Participants maintained physical activity levels once the program was completed. Combining physical training with our cognitive-behavioral intervention did not add to these beneficial effects of physical training neither in the short-term nor in the long-term. Physical training should be implemented within the framework of standard care for cancer survivors.


Weilby tendon interposition arthroplasty for osteoarthritis of the trapezial joints.
Primary osteoarthritis of the trapezial joints has been treated by an interposition tendoplasty according to Weilby in eighty-nine cases. After excision of the trapezium, a strip from the flexor carpi radialis was wound around the main portion of the flexor carpi radialis tendon and the abductor pollicis longus. The abductor tendon was then duplicated over the tendoplasty and reinserted to the first metacarpal base. In 40% of cases, osteoarthritis was present in more than one trapezial joint. 57% had an adduction contracture of the first metacarpal, half of which were relieved postoperatively. 73% of patients were satisfied at follow-up. Complications included four cases with loss of active metacarpal abduction which was regained after reinsertion of the abductor pollicis longus. It is concluded that the Weilby tendoplasty is a useful alternative to Silastic implants, especially in cases of adduction contracture. The risks of implant dislocation and silicone synovitis are eliminated.


Th17 and Treg lymphocytes in obesity and Type 2 diabetic patients.
Assumption that the pathogenesis of obesity-associated type 2 diabetes (T2DM) encompasses inflammation and autoimmune aspects is increasingly recognized. In the state of obesity and T2DM, the imbalance of T helper 17 (Th17) cells and regulatory T (Treg) cells are observed. These alterations reflect a loss of T cell homeostasis, which may contribute to tissue and systemic inflammation and immunity in T2DM. In this review we will discuss the accumulating data supporting the concept that Th17/Treg mediated immune responses are present in obesity-related T2DM pathogenesis, and provide evidences that restoration of Th17/Treg imbalance may be a possible therapeutic avenue for the prevention and treatment of T2DM and its complications.


Socioeconomic disparities in treatment and survival in patients with hypopharyngeal malignancy.
This retrospective study utilizes The Surveillance, Epidemiology, and End Results database to investigate socioeconomic factors leading to treatment disparities in hypopharyngeal malignancy. Treatment was compared to National Cancer Care Network guidelines. Novel analyses, including logistic modeling, allowed survival analysis and identification of socioeconomic variables not previously considered in staging and management guidelines. Black and older patients, and residence in low-income areas predict lower likelihood of standard therapy (p < 0.05). Early-stage disease and standard therapy correlate with improved survival (p < 0.001). Medicaid, advanced age, advanced disease, and treatment outside of consensus guidelines correlated with lower survival (p < 0.0001). There are clear socioeconomic factors impacting treatment and survival in hypopharyngeal malignancies. Standard therapy affords superior survival rate. Black, low socioeconomic status, and older patients are less likely to receive standard therapy. Education and language isolation do not predict treatment or survival. Understanding these discrepancies is paramount to palliating disparities in healthcare.


Pathological diagnosis, differential diagnosis and origin investigation of easily misdiagnosed adult gastric duplication cysts.
To study diagnosis, differential diagnosis, and origin of easily misdiagnosed adult gastric duplication cysts. Six cases with GDCs were studied using immunohistochemical methods to research the expression of tumor markers. Most GDCs were located in the abdominal cavity outside the digestive organs. The cyst wall tissues included a repetition of the full-thickness structure of the stomach wall that was lined by a variety of different epithelia. The expression of CK7 was positive in all epithelia (6/6), while CK7 expression was positive in cardia glands in 5/5 and positive in fundus glands in 1/5. CK 20 was 100% (4/4) positively expressed in the SCE, 100% (3/3) negative in the CCE, and in the SE. It was also expressed positively 100% (5/5) in fundus glands and 80% (4/5) in cardia glands. Both CK7 and CK20 were negatively expressed in the pyloric glands in case 3. The expression of MUC1 was positive in all epithelia and glands, whereas MUC2 expression was negative. MUC5AC was expressed differently in epithelia and glands. GDCs can originate from the antrum or the fundus of the stomach. Tumor markers can help diagnosis and differential diagnosis. This study may help to improve clinical precision treatment.


Update on adolescent immunization: review of pertussis and the efficacy, safety, and clinical use of vaccines that contain tetanus-diphtheria-acellular pertussis.
Adolescents, who comprise 14% of the US population, are historically resistant to receiving health care. As a result, adolescents have low immunization rates and are becoming more susceptible to diseases that are preventable by vaccine, such as pertussis. The incidence of pertussis has increased during the past 25 years, with a notable shift in incidence from young children to adolescents and young adults. New vaccines that provide protection against pertussis for use in adolescents have been proven to be safe, effective, and cost-beneficial. Regional epidemics among infants and other vulnerable populations can be reduced or eliminated with improved immunity in adolescents.


Acupuncture Modulates Disrupted Whole-Brain Network after Ischemic Stroke: Evidence Based on Graph Theory Analysis.
Stroke can lead to disruption of the whole-brain network in patients. Acupuncture can modulate the functional network on a large-scale level in healthy individuals. However, whether and how acupuncture can make a potential impact on the disrupted whole-brain network after ischemic stroke remains elusive. 26 stroke patients with a right hemispheric subcortical infarct were recruited. We gathered the functional magnetic resonance imaging (fMRI) from patients with stroke and healthy controls in the resting state and after acupuncture intervention, to investigate the instant alterations of the large-scale functional networks. The graph theory analysis was applied using the GRETNA and SPM12 software to construct the whole-brain network and yield the small-world parameters and network efficiency. Compared with the healthy subjects, the stroke patients had a decreased normalized small-worldness (σ), global efficiency (E g), and the mean local efficiency (E loc) of the whole-brain network in the resting state. There was a correlation between the duration after stroke onset and E loc. Acupuncture improved the patients' clustering coefficient (C p) and E loc but did not make a significant impact on the σ and E g. The postacupuncture variables of the whole-brain network had no association with the time of onset. The poststroke whole-brain network tended to a random network with reduced network efficiency. Acupuncture was able to modulate the disrupted patterns of the whole-brain network following the subcortical ischemic stroke. Our findings shed light on the potential mechanisms of the functional reorganization on poststroke brain networks involving acupuncture intervention from a large-scale perspective.


The role of blink reflex R1 latency as an electrophysiological marker in diabetic distal symmetrical polyneuropathy.
Studies showed a relatively prolonged blink R1 latency in patients with diabetic distal symmetrical polyneuropathy (DSPN) compared to that without DSPN. We tested the hypothesis that blink R1 latency would provide a diagnostic alternative to nerve conduction studies (NCS) in DSPN and act as a marker of the severity of NCS abnormalities in DSPN. A total of 109 patients with type 2 diabetes underwent blink reflex studies and NCS. We used the composite amplitude scores of nerve conductions (CAS), which consisted of motor (tibial, peroneal and ulnar) and sensory (sural and ulnar) amplitudes for estimating the severity of NCS. Patients with DSPN had longer blink R1, R2, and contralateral R2 latencies (P < 0.0001, P = 0.001, and P = 0.031, respectively) and higher CAS (P < 0.0001). Area under curve on receiver operating characteristic curve analysis in diagnosing occurrence of DSPN in blink R1 latency was 0.772 (P < 0.0001). Multiple linear regression analysis showed that blink R1 latency was independently associated with CAS. Blink R1 latency may be valuable in auxiliary diagnosis and in determining the severity of NCS abnormalities in DSPN. Blink R1 latency can be added as a supplemental marker of severity of NCS in DSPN, especially if the patient's sural amplitudes has a floor effect.


What could possibly go wrong? - A heuristic for predicting population health outcomes of interventions.
Austin Bradford Hill offers a general heuristic for causal inference in epidemiology, but no general heuristic for prediction is available. This paper seeks to identify a heuristic for predicting the outcome of interventions on population health, informed by the moral context of such interventions. It is suggested that, where available, robust predictions should be preferred, where a robust prediction is one which, according to the best knowledge we are currently able to obtain, could not easily be wrong. To assess whether a prediction is robust, it is suggested that we ask why the predicted outcome will occur, rather than any other outcome. Firstly, if, according to our current knowledge, we cannot identify the likeliest ways that the other outcomes could occur, then the prediction is not robust. And secondly, if, according to our current knowledge, we can identify the likeliest other outcomes but we are unable to say why our predicted outcome will occur rather than these, then, again, our prediction is not robust. Otherwise, it is robust. The inaccurate but memorable short version of the heuristic is, "What could possibly go wrong?"


The Mutational Features of Aristolochic Acid-Induced Mouse and Human Liver Cancers.
Aristolochic acid (AA) exposure has been statistically associated with human liver cancers. However, direct evidence of AA exposure-induced liver cancer is absent. This study aims to establish a direct causal relationship between AA exposure and liver cancers based on a mouse model and then explores the AA-mediated genomic alterations that could be implicated in human cancers with AA-associated mutational signature. We subjected mice, including phosphatase and tensin homolog (Pten)-deficient ones, to aristolochic acid I (AAI) alone or a combination of AAI and CCl4 . Significantly, AAI exposure induced mouse liver cancers, including hepatocellular carcinoma (HCC) and combined HCC and intrahepatic cholangiocarcinoma, in a dose-dependent manner. Moreover, AAI exposure also enhanced tumorigenesis in these CCl4 -treated or Pten-deficient mice. AAI led to DNA damage and AAI-DNA adduct that could initiate liver cancers through characteristic adenine-to-thymine transversions, as indicated by comprehensive genomic analysis, which revealed recurrent mutations in Harvey rat sarcoma virus oncogene. Interestingly, an AA-associated mutational signature was mainly implicated in human liver cancers, especially from China. Moreover, we detected the AAI-DNA adduct in 25.8% (16/62) of paratumor liver tissues from randomly selected Chinese patients with HCC. Furthermore, based on phylogenetic analysis, the characteristic mutations were found in the initiating malignant clones in the AA-implicated mouse and human liver cancers where the mutations of tumor protein p53 and Janus kinase 1 were prone to be significantly enriched in the AA-affected human tumors. This study provides evidence for AA-induced liver cancer with the featured mutational processes during malignant clonal evolution, laying a solid foundation for the prevention and diagnosis of AA-associated human cancers, especially liver cancers.


4-Amino-5-(2-hydroxy-4,4-dimethyl-6-oxocyclohexenylmethyl)-1-methyl-2-(methylsulfanyl)pyrimidin-6(1H)-one: hydrogen-bonded chains are pi-stacked in pairs.
Molecules of the title compound, C15H21N3O3S, have a markedly polarized electronic structure; the carbocyclic ring adopts an envelope conformation and the overall molecular conformation appears to be controlled by two intramolecular hydrogen bonds, one each of the O-H...O and N-H...O types. The molecules are linked into C(6) chains by an intermolecular N-H...O hydrogen bond, and pairs of these hydrogen-bonded chains are linked by a pi-pi stacking interaction.


The rating of symptoms by a psychiatrist and a non-psychiatrist: a study of patients referred from general practice.
A psychologist interviewing patients referred to the psychiatric service of a health centre rated twice as much morbidity, measured by total PSE score, as a psychiatrist interviewing equivalent patients. Scores on the self-rated GHQ showed no difference between the 2 groups. It is suggested that such differences could be avoided by giving careful attention to training interviewers.


Vinpocetine (A comprehensive profile).
Vinpocetine (VIN) is a herbal supplement extracted from the periwinkle plant. It is a multi-action agent, which is used to treat various neurological disorders such as Alzheimer's and Parkinson's disease. Vinpocetine has also anti-inflammatory, analgesic, antioxidant property and treats various thinking and memory problems. Currently, vinpocetine is also available in the market as a dietary supplement to enhance cognition and memory. This profile explains the physicochemical properties, methods of preparation, content of related impurities and different spectroscopical behavior of vinpocetine. It also discusses the reported methods of analysis of the drug, which include Compendial Methods, Electrochemical Methods, Spectrophotometric Methods and Chromatographic Methods of analysis. Furthermore, this profile explains the stability of the drug subjected to stress conditions of acid, alkaline and photolytic degradation. In addition, the clinical applications of the drug, its uses, side effects, dosing information, pharmacokinetics and mechanism of action are also discussed.


Classification and Morphological Analysis of the Hard Palate in Cone-Beam Computed Tomography Scans: A Retrospective Study.
As the hard palate is a central structure of the skull and is involved in orthodontic and surgical procedures, it would be of interest to study the morphological aspects of this bone and its possible variations as per different patterns of skeletal development. Thus, this study aimed to develop a classification for the different morphological characteristics of the hard palate and to evaluate the relationship between these characteristics and the different skeletal patterns, using cone-beam computed tomography (CBCT). This retrospective and cross-sectional study used CBCT scans of patients seen from January 2014 to December 2016. Carestream Dental 3D Imaging software was applied to classify each patient according to vertical and sagittal skeletal patterns, and to evaluate the 3 morphological characteristics of the hard palate: depth (flat, regular, or deep), inclination (superior, parallel, or inferior), and presence of a bony projection (S-shaped). χ2 and Fisher's exact tests evaluated the relationship between the hard palate characteristics and the different skeletal patterns. A total of 298 CBCT scans (144 males and 154 females) were evaluated. The depth of the hard palate was significantly related to both skeletal patterns in males (P < .05), with Class II and dolichocephalics presenting a greater amount of deep palates, while classes I and III and brachycephalics had a greater amount of regular palates. The inclination of the hard palate was significantly associated with the facial type in females (P < .05), with brachycephalics and mesocephalics presenting a greater amount of parallel palates, whereas dolichocephalics had a greater number of inferiorly inclined palates. Regarding the presence of the S-shape in the hard palate, there was a greater number of this projection in Class II males and brachycephalic females. A morphological classification for the hard palate was developed. The morphology of the hard palate varied among the different skeletal patterns.


Experimental Study of the Effect of Biological Matrixes with Stabilized and Non-Stabilized Platelets on Reparative Process in the Wound Equivalent to Deep Burn.
We studied reparative effect of platelet-filled biological matrixes in the treatment of mice with wounds equivalent to deep burn. The wound coatings were based on decellularized dermal matrix without platelets (control), with native platelets, and with platelets stabilized with 2.5 μM nanosilver. In 3 days, the epithelial layer and derma were absent in all groups and extensive scab was formed. Dermal matrix with platelets simulated intensive migration of macrophages and fibroblasts to the wound bottom; in the control group, this migration was absent. In 14 days, granulation tissue appeared in the wound bottom in animals of all groups; in the experimental groups, the number of vessels was 2-4-fold higher than in the control, though the number of inflammatory cells in experimental groups remained high. On day 21, the scab on the most of the wound area was absent in all animals of the experimental groups and epithelialization and hair growth were pronounced, comparing to control. Nevertheless, in experiment dermal layer was not already completed, inflammation reaction remained.


The effects of non-steroidal anti-inflammatory drugs on cholinergic and histamine-induced contractions of guinea-pig isolated ileum.
1 Eleven non-steroidal anti-inflammatory drugs (NSAID) reversibly inhibited contractions of the longitudinal muscle of the guinea pig isolated ileum induced by acetylcholine, histamine, electrical transmural stimulation and nicotine in this order of increasing potency. 2. After the addition of prostaglandins E1, E2 or F2alpha, with partially effective concentrations of NSAID (but not with higher concentrations which almost totally prevented the responses) the inhibitory effects of NSAID were reversibly lost, except for electrically induced contractions and prostaglandin F2alpha. 3 The effects of NSAID may be due to actions on biological membranes or on distribution of ions in addition to their inhibitory effect on prostaglandin synthesis. Prostaglandins may reverse the inhibition by non-selective sensitization of smooth muscle to various agonists.


Multiplex polymerase chain reaction for human herpesvirus-6, human cytomegalovirus, and human beta-globin DNA.
Human cytomegalovirus and human herpesvirus-6 are closely related viruses which cause similar diseases, have similar cellular repositories of latent infection, and may be detected largely in the same types of clinical specimens. DNA amplification appears likely to play an increasing role in the diagnosis of recent and remote infection with these agents. A sensitive multiplex polymerase chain reaction was therefore developed for the two viruses and for human beta-globin DNA. Optimization of parameters such as the primers, primer concentrations, magnesium concentration, and buffer constituents was crucial in achieving a sensitive assay. Preliminary results indicated that the assay could simultaneously monitor DNA extraction from clinical specimens and allow detection of HCMV or HHV-6 in patients with diseases possibly caused by either pathogen.


The generation and differentiation of cholinergic neurons in rat caudate-putamen.
By combining [3H]thymidine autoradiography with choline acetyltransferase (ChAT) immunocytochemistry, we have determined the generation pattern of the large cholinergic neurons in the neostriatum. All of these neurons are produced between embryonic days 12 and 17 (E12-E17), with 75% of them being born between E13 and 15. Cholinergic neurons appeared to be among the earliest cells produced in the neostriatum when compared with previous generation studies of all neurons in the rat caudate-putamen. The caudal-to-rostral neurogenic gradient reported in previous investigations of all neurons was the only spatiotemporal gradient observed for cholinergic neurons. The generation peak for these cells was E13 caudally, and E15 rostrally. Additional immunocytochemical studies detected ChAT immunoreactivity within somata and primary dendrites of 1 day postnatal (1 dpn) rat neostriatum, and subsequently demonstrated a dramatic increase in the intensity of reaction product and the complexity of dendritic arborizations by 14 dpn. Large ChAT-positive neurons of the basal forebrain contained within the same specimens appeared to differentiate their cholinergic phenotype earlier than those in the neostriatum. However, recent generation studies of basal forebrain neurons combined with the present results have demonstrated that both cholinergic populations are produced simultaneously along the same neurogenic gradients. This then represents an example of cholinergic projection (basal forebrain system) and local circuit (neostriatum) neurons that share similar generation patterns but differ with respect to sequences of transmitter phenotype expression. Thus, for cholinergic forebrain neurons, a cell's position along the neurogenic gradient and its transmitter phenotype appear to be more closely associated with its birth date than its ultimate projection or rate of differentiation.


Impact of Pool Testing in Detection of Asymptomatic Patients with COVID-19.
During the current pandemic, COVID-19 has been detected in patients using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) that confirms the presence of SARS-CoV-2 RNA. The demand for increased testing, particularly for asymptomatic individuals required alternative approaches to single-patient RT-PCR testing, such as pooling. This study explored the impact of dilution on the detectability of SARS-CoV-2 in asymptomatic patients using RT-PCR and demonstrated that pooling can be effective in low prevalence populations. The RT-PCR results for the 3:1, 5:1, and 7:1 aliquot samples showed little differences in CT values, confirming detection capability at these dilutions. Based on the results of the present study, a pooled approach with up to 5:1 sample aliquots and using the current RT-PCR methodology likely will detect SARS CoV2 RNA among asymptomatic patients.


Morphometric assessment of normal human ciliary body using ultrasound biomicroscopy.
To quantitatively assess the biometry of the ciliary body in normal human eyes using ultrasound biomicroscopy. We evaluated 85 eyes of 85 normal subjects (35 men and 50 women), whose age ranged from 11 to 86 years (mean ± SD, 56.8 ± 20.4 years). The eyes were assessed along the 3-, 6-, 9-, and 12-o'clock meridians relative to the center of the cornea. Clinical data were collected, including age, axial length, ciliary body length (CBL), ciliary body thickness (CBT), anterior chamber depth, iris root thickness, trabecular-iris angle, and scleral-ciliary process angle. Axial length was measured using A-scan ultrasonography. CBL and CBT tended to be larger in the superior than in the inferior quadrant, but the differences among the four quadrants were not statistically significant. The average CBL showed a significant positive correlation with the average CBT (r = 0.40, P < 0.001). Average CBL and CBT were significantly correlated with axial length (r = 0.33, P = 0.031; r = 0.46, P < 0.01 respectively). In addition, the average CBL was significantly correlated with anterior chamber depth (r = 0.23, P < 0.05), trabecular-iris angle (r = 0.29, P = 0.01), and scleral-ciliary process angle (r = 0.40, P < 0.001). Ultrasound biomicroscopic imaging demonstrated that the ciliary body is similar in size in all circumferences, and eyes with longer axial length have an elongated and thicker ciliary body. The values obtained in the present study may serve as standard clinical references.


Quantum-spin-liquid states in the two-dimensional kagome antiferromagnets ZnxCu4-x(OD)6Cl2.
A three-dimensional system of interacting spins typically develops static long-range order when it is cooled. If the spins are quantum (S=1/2), however, novel quantum paramagnetic states may appear. The most highly sought state among them is the resonating-valence-bond state, in which every pair of neighbouring quantum spins forms an entangled spin singlet (valence bonds) and these singlets are quantum mechanically resonating among themselves. Here we provide an experimental indication for such quantum paramagnetic states existing in frustrated antiferromagnets, Zn(x)Cu(4-x)(OD)(6)Cl(2), where the S=1/2 magnetic Cu2+ moments form layers of a two-dimensional kagome lattice. We find that in Cu(4)(OD)(6)Cl(2), where distorted kagome planes are weakly coupled, a dispersionless excitation mode appears in the magnetic excitation spectrum below approximately 20 K, whose characteristics resemble those of quantum spin singlets in a solid state, known as a valence-bond solid, that breaks translational symmetry. Doping with non-magnetic Zn2+ ions reduces the distortion of the kagome lattice, and weakens the interplane coupling but also dilutes the magnetic occupancy of the kagome lattice. The valence-bond-solid state is suppressed, and for ZnCu(3)(OD)(6)Cl(2), where the kagome planes are undistorted and 90% occupied by the Cu2+ ions, the low-energy spin fluctuations become featureless.


A dual-zwitterion functionalized ultra-hydrophilic metal-organic framework with ingenious synergy for enhanced enrichment of glycopeptides.
A rational strategy was introduced for the synthesis of a novel dual functionalized metal-organic framework nanocomposite (AuGC/ZIF-8) with ultra-hydrophilicity to enhance glycopeptide enrichment. The advantages of ingenious synergy, low-cost, facile and large-scale synthesis, and excellent enrichment performance will enable it to have a bright future in nanomaterial synthesis, glycoproteomics analysis, and related biochemistry.


Sulindac enhances tumor necrosis factor-alpha-mediated apoptosis of lung cancer cell lines by inhibition of nuclear factor-kappaB.
Programmed cell death (apoptosis) is induced by certain anticancer therapies, and resistance to apoptosis is a major mechanism by which tumors evade these therapies. The transcription factor nuclear factor (NF)-kappaB, which is frequently activated by treatment of cancer cells with different chemotherapeutic agents, promotes cell survival, whereas its inhibition leads to enhanced apoptosis. Recently, sulindac and other nonsteroidal anti-inflammatory drugs have been shown to inhibit tumor necrosis factor (TNF)-alpha-mediated NF-kappaB activation. Here, we demonstrate that treatment of the non-small cell lung carcinoma cells NCI-H157 and NCI-H1299 with sulindac greatly enhances TNF-alpha-mediated apoptosis. We further show that sulindac inhibits TNF-alpha-mediated activation of NF-kappaB DNA binding and nuclear translocation of NF-kappaB. These results suggest that sulindac and other nonsteroidal anti-inflammatory drug inhibitors of NF-kappaB activation may serve as useful agents in cancer chemotherapy.


Advanced Image-Guided Procedures for Painful Spine.
In addition to basic image-guided injections, there are many advanced procedures to address the challenges of spine pain. Patients with debilitating symptoms are offered relief, a shorter recovery period, and fewer potential complications. Pain arises from numerous sites along the spine, presenting as spine pain or radiculopathy. This article is an overview of advanced techniques in this rapidly progressing field, including neuromodulation, radiofrequency thermocoagulation, discography, intradiscal thermocoagulation, and percutaneous image-guided lumbar decompression; and it highlights etiologic factors and their relationship to therapeutic technique and clinical evidence.


Formation of hematopoietic territories and bone by transplanted human bone marrow stromal cells requires a critical cell density.
Bone marrow stromal cells (BMSCs) include multipotent cells with the ability to form mature bone organs upon in vivo transplantation. Hematopoiesis in these bone organs has been ascribed to the action of skeletal stem cells, which are capable of differentiating towards bone and hematopoiesis-supporting stroma. Yet, the creation of hematopoietic territories may be in part a natural consequence of the formation of a sufficiently mature and large bone microenvironment. Here, we describe, for the first time, a relationship between BMSC numbers and the extent of bone/hematopoiesis formation in heterotopic transplants. Human BMSCs were transplanted along with hydroxyapatite/tricalcium phosphate, utilizing a spectrum of dosages, into immunotolerant mice; the transplants were followed for up to 29 months. The extent of bone and hematopoiesis formation increased with increasing BMSC numbers; however, the relationship was sigmoid in character, and a threshold number of BMSCs was necessary for extensive bone formation or any hematopoiesis. Hematopoiesis only occurred in conjunction with extensive bone formation, and no hematopoiesis occurred where bone formation was poor. Consistent with our earlier studies of long-term BMSC transplantation, the transplants underwent a change in bone morphology but not bone content after 8 weeks. Our results have provided evidence that the formation of both hematopoiesis and a mature bone organ is as much a consequence of a sufficiently high local density of bone marrow stromal cells as it is the product of skeletal stem cell action.


Development and validation of a questionnaire for anxiety and depression in Pakistan.
Currently clinicians and researchers in Pakistan have to use translated western instruments to screen for anxiety and depressive disorders. This study investigated the local idioms of emotional distress in Pakistan to develop a culturally valid and easy-to-use instrument to screen for common mental disorders in general clinical settings. A systematic survey was conducted of psychiatric case notes of patients attending clinics in Peshawar and Lahore, diagnosed with anxiety or depressive disorders, to identify the range of common idioms of psychological distress. A pilot version of the questionnaire was refined and validated among a composite sample of 330 patients in inpatient, outpatient and rural community settings. ICD-10 Diagnostic Criteria for Research were used to define cases and patients' relatives acted as normal controls. The pilot version of the questionnaire was reduced to 42 items based on odds ratios between cases and controls. Anxiety symptoms were generally reported by depressed patients, but not vice versa. Finally 30 items were selected, in two sub-scales. This final version achieved sensitivity, specificity, and positive and negative predicted values of over 90% when comparing cases and controls. This questionnaire was based on what patients tell doctors and may not capture the entire repertoire of local idioms of distress. The validation study was conducted only in an Urdu/Punjabi speaking population, in Lahore and surrounding areas. The Pakistan Anxiety and Depression Questionnaire consists of an anxiety/depression scale and a depression scale, each of 15 items. It demonstrates excellent validity as screening instrument for anxiety and depressive disorders in clinical settings in Pakistan.


The GABAA receptor channel mediated chloride ion translocation through the plasma membrane: new insights from 36Cl- ion flux measurements.
GABAA receptors in plasma membranes of neurons are integral oligomers which form chloride channels. The binding of GABA molecules at recognition sites for channel opening triggers a transient increase in transmembrane chloride ion flux. The multiplicity and drug specificity of GABAA receptor, kinetics of channel opening, and desensitization of GABAA receptor and its short- and long-term regulation have been investigated by the use of tracer amounts of the radioactive chloride isotope, 36Cl- ion. Results and new insights from 36Cl- ion flux measurements have been reviewed.


Measurement in the angiography suite: evaluation of vessel sizing techniques.
Accurate vessel size measurement is important for neurointervention. Modern angiographic equipment offers various two-dimensional (2D) and 3D measurement methods that have not been systematically evaluated for accuracy and reliability. To evaluate these methods using anthropomorphic vessel phantoms. Tubing of known sizes (2-5 mm, 1 mm increments) was embedded in 3D-printed skulls to simulate the middle cerebral artery, internal carotid artery, and basilar artery. Each phantom was imaged to gain 3D DSA, 2D DSA, and DynaCT images. Three identical measurement locations were identified on each simulated vessel. Eight measurement methods (four 2D, three 3D, and one DynaCT) were evaluated. Measurements were performed by three independent experienced users on three separate occasions. Intraclass correlation and independent non-parametric analysis were carried out to evaluate the reliability and accuracy of these measurement methods. Better reliability was noted for the automatic measurement methods than for the corresponding manual measurement methods. The mean differences with the ground truth for all methods ranged from -0.12 to 0.03 with small SEs (0.02-0.03) and SDs (0.10-0.18). The smallest absolute mean differences were achieved in two automatic measurement methods based on 2D manual calibration and 3D images. In comparison with these two methods, results of measurements based on 2D autocalibration were statistically different. In our study, automatic analysis using 3D or 2D was the preferred measurement method. Manual calibration on 2D angiograms is necessary to improve the measurement accuracy. It is not known how our results may pertain to other angiographic systems.


Electrochemical investigations of baicalin and DNA-baicalin interactions.
Baicalin is an anti-HIV drug purified from the traditional Chinese medicinal plant Scutellaria Baicalensis Georgi. Baicalin has proven to be electroactive at pyrolytic graphite (PG) electrodes. We thus studied its interaction with DNA via the electrochemical approach. We observed that the peak currents corresponding to the baicalin reduction-oxidation (redox) reaction significantly decrease upon the addition of DNA. With complementary ultraviolet/visible (UV/Vis) spectroscopic evidence, we suggest that baicalin binds to DNA through intercalation. This feature has enabled baicalin to discriminate between double-stranded DNA (dsDNA) and single-stranded DNA (ssDNA).


The second species of Gromia (Protista) from the deep sea: its natural history and association with the Pakistan margin oxygen minimum zone.
We describe a gromiid protist Gromia pyriformis sp. nov., from bathyal depths on the Pakistan margin (NE Arabian Sea), an area characterised by a well-developed Oxygen Minimum Zone (OMZ). The new species is smaller (length usually <1 mm) than the only other described deep-sea gromiid species (Gromia sphaerica) or the well-known coastal species Gromia oviformis. Its identification as a gromiid is based on the test-wall ultrastructure. This includes (i) an outer wall (165-300 nm thick) limited by an electron-opaque layer and perforated by pore structures which typically extend through its entire thickness, and (ii) inner "honeycomb membrane" structures which form a discontinuous sheet (18-20 nm thick) lying parallel to the outer wall. An outermost glycocalyx (approximately 75 nm thick), not observed in other gromiid species, is also present and imparts a finely granular appearance to the outer test surface, as seen by Scanning Electron Microscopy (SEM). Numerous rod-shaped prokaryotes are attached to the exterior of the glycocalyx. Gromia pyriformis sp. nov. typically occurs above the sediment-water interface, attached to the large arborescent foraminiferan Pelosina sp. It is confined to a very narrow bathymetric zone (approximately 1000 m water depth) in the lower portion of the OMZ, where bottom-water oxygen concentrations are approximately 0.2 ml l(-1).


Molecular basis of essential amino acid transport from studies of insect nutrient amino acid transporters of the SLC6 family (NAT-SLC6).
Two protein families that represent major components of essential amino acid transport in insects have been identified. They are annotated as the SLC6 and SLC7 families of transporters according to phylogenetic proximity to characterized amino acid transporters (HUGO nomenclature). Members of these families have been identified as important apical and basolateral parts of transepithelial essential amino acid absorption in the metazoan alimentary canal. Synergistically, they play critical physiological roles as essential substrate providers to diverse metabolic processes, including generic protein synthesis. This review briefly clarifies the requirements for amino acid transport and a variety of amino acid transport mechanisms, including the aforementioned families. Further it focuses on the large group of Nutrient Amino acid Transporters (NATs), which comprise a recently identified subfamily of the Neurotransmitter Sodium Symporter family (NSS or SLC6). The first insect NAT, cloned from the caterpillar gut, has a broad substrate spectrum similar to mammalian B(0) transporters. Several new NAT-SLC6 members have been characterized in an effort to explore mechanisms for the essential amino acid absorption in model dipteran insects. The identification and functional characterization of new B(0)-like and narrow specificity transporters of essential amino acids in fruit fly and mosquitoes leads to a fundamentally important insight: that NATs evolved and act together as the integrated active core of a transport network that mediates active alimentary absorption and systemic distribution of essential amino acids. This role of NATs is projected from the most primitive prokaryotes to the most complex metazoan organisms, and represents an interesting platform for unraveling the molecular evolution of amino acid transport and modeling amino acid transport disorders. The comparative study of NATs elucidates important adaptive differences between essential amino acid transportomes of invertebrate and vertebrate organisms, outlining a new possibility for selective targeting of essential amino acid absorption mechanisms to control medically and economically important arthropods and other invertebrate organisms.


Intracranial extra-axial hemangioma in a newborn: A case report and literature review.
Congenital hemangiomas are benign vascular tumors, and the intracranial counterpart was described in very few cases. A newborn presented with an intracranial tumor associated with an arachnoid cyst, diagnosed by antenatal ultrasound at 37 weeks of gestation. Surgery was indicated due to increased head circumference and bulging fontanelle, and a complete resection of an extra-axial red-brown tumor was performed at the 3(rd) week of life. Microscopy revealed a hemangioma. Hemangioma is a rare differential diagnosis that must be considered in extra-axial intracranial tumors affecting infants and neonates. The radiological features are not helpful in differentiating from other tumors, and surgery is indicated when the diagnosis is uncertain or whenever there are signs of increased intracranial pressure.


A coherent synchrotron X-ray microradiology investigation of bubble and droplet coalescence.
A quantitative application of microradiology with coherent X-rays to the real-time study of microbubble and microdroplet coalescence phenomena, with specific emphasis on the size relations in three-body events, is presented. The results illustrate the remarkable effectiveness of coherent X-ray imaging in delineating interfaces in multiphase systems, in accurately measuring their geometric properties and in monitoring their dynamics.


Implications of disparate uterine and ovarian development observed among heifers evaluated during the peripubertal period.
The incidence and implications of disparate ovarian and uterine development during the peripubertal period were evaluated in two experiments. In Experiment 1, two consecutive pre-breeding evaluations were performed on 469 heifers. In Experiment 2, data from 22,174 heifers were retrospectively analyzed. For heifers in both experiments, ovarian and uterine maturity were independently assessed via transrectal evaluation, and a two-digit reproductive tract score (RTS: first digit = ovarian; second digit = uterine) was assigned. Measures of the physical maturity of heifers were recorded at the time of pre-breeding evaluation. Heifers were subjected to 14-day progestin-based protocols for synchronization of estrus, and artificial insemination (AI) was performed. Pregnancy diagnosis was performed via transrectal ultrasonography. Incidence of disparate ovarian and uterine score was 33.7 % (158/469) in Experiment 1 % and 16.3 % (3622/22,174) in Experiment 2. Observations of disparate ovarian and uterine maturity were correlated with physical maturity. Heifers with RTS < 3-3 demonstrated poor reproductive performance, as lesser proportions of these animals conceived to the first AI service in Experiment 2 (P < 0.01) or throughout the breeding season in Experiment 1 (P = 0.03). Conception did not differ between heifers assigned congruent or disparate scores of greater than RTS = 3-3. Disparities in ovarian and uterine development are likely observed as the result of rapid, yet asynchronous growth of reproductive tissues during the peripubertal period and are not indicative of inherently reduced potential for fertility. Independent assessment of ovarian and uterine maturity may increase precision in characterizing physiologic maturity of mixed groups of prepubertal, peripubertal, and pubertal heifers.


Acute exposure to graded levels of hypoxia in rainbow trout (Salmo gairdneri): metabolic and respiratory adaptations.
We have studied the mechanisms of acute hypoxia tolerance in rainbow trout (Salmo gairdneri). Fish held at 9 degrees C were exposed to various levels of hypoxia for 24 h. At an environmental PO2 of 30 Torr, the fish showed an initial plasma acidosis probably of metabolic origin which was subsequently offset such that blood pH returned to normal within about 4 h. Over this time period, red cell pH was maintained constant. Comparing the effects of different levels of hypoxia following 24 h exposure, oxygen consumption of the animal remained unchanged over a broad range of inspired oxygen tensions but declined by over 30% of normoxic values at inspired water PO2 levels of 80 Torr. This appeared to be a true metabolic depression because signs of increased anaerobic metabolism did not occur until there was a further reduction in water oxygen levels. Rainbow trout appear to be able to maintain a relatively high energy status in their white muscle during 24 h exposure to severe hypoxia (water PO2 = 30 Torr). As the level of hypoxia was intensified, there was a reduction in the oxygen gradient across the gills, probably facilitated in part by the release of catecholamines into the blood. The erythrocytic ATP: Hb4 molar ratios declined with increasing hypoxic stress as did the pH gradient between the erythrocyte and plasma. The overall effect was no change in Hb O2-affinity after 24 h exposure to severe hypoxia.


Sex differences due to dehydroepiandrosterone (DHEA) feeding affecting dehydroepiandrosterone sulfate secretion in golden Syrian hamsters.
The metabolism of orally administered dehydroepiandrosterone (DHEA) by male and female golden Syrian hamsters was examined by quantification of DHEA and dehydroepiandrosterone sulfate (DHEAS) in gallbladder bile, urine and feces using high-performance liquid chromatography (HPLC). Plasma levels of DHEA and DHEAS were also determined by radioimmunoassay (RIA). After 5 days of oral DHEA administration (100 mg/kg body weight twice a day), RIA showed that plasma levels of DHEA and DHEAS were increased approximately 3-6 and 4-5 times, respectively, compared to controls. More than 95 % of circulating DHEA (S) in the peripheral blood was DHEAS. There was no significant sex difference in DHEAS plasma levels between male and female animals in the DHEA-supplemented group. However, 0.2 - 0.3 % of ingested DHEA was conjugated to DHEAS and excreted in urine by females, whereas less than 0.002 % was excreted in urine by males (p < 0.005). DHEAS was excreted in bile by males after DHEA supplementation, and the sex differences in DHEAS levels observed in bile were statistically significant (male, 18.7 +/- 7.5 vs. female, 5.6 +/- 3.1 micromol/l) (p < 0.005). Small amounts of ingested DHEA were excreted in an unchanged state in feces, and no sex difference was observed. These results suggest that there is a considerable sex difference in the conjugation and excretion of orally administered DHEA in the hamster.


Maximising medicine through aphorisms.
Aphorisms are succinct sayings that offer advice. They have permanently coloured medical culture and inhabit it in the same way as uncertainty; they are acknowledged, but rarely explored. Little has been written analytically or critically about the meanings and purposes of aphorisms in contemporary medical education, especially as a processional activity that maintains tradition, but both adds to and reframes it. We note multiple purposes for medical aphorisms, including roles as heuristics (rules of thumb) for practice, and in the identity construction of the clinician within a community beset by professional uncertainty and accountability. We suggest that aphorisms should be cared for not simply as historical curiosities, but as renewable ways of creating an 'art of memory' in medical education, stimulating recognition and recall as aesthetic rhetorical devices. In this spirit, we encourage the development of aphorisms appropriate for 21st century medicine in a process that should include the involvement of patients in building a proxy public literacy to inform collaboration in clinical encounters. We propose a novel framework for aphorisms, emphasising strategies to enhance or maximise clinical judgement and professional behaviour, affirm identities, and educate the public via the media.


Assessment of scaling and corrosion potential of drinking water resources of Iranshahr.
The aim of this study was to evaluate corrosion and scaling potential of drinking water resources Iranshahr in order to considering necessary solutions to solve possible problems including internal corrosion of pipes, deterioration of water quality and reduce of water transfer capacity of distribution network system. The data showed that Langelier index ranged between -1.53 to -0.96, Ryznar index between 9.63-10.54, Aggressive index between 12.04 and 12.91, and Puckorius index between 9.05-10.68 for drinking water resources Iranshahr. Studied indices indicated that the drinking water in Iranshahr can be considered as corrosive.


Metabolism of purine nucleosides and phosphoribosylpyrophosphate in thymocytes and splenocytes of various mammalian species.
1. Activities of ADA, PNP and AK were measured in splenocytes and thymocytes of newborn children, young horses, pigs, sheep, rats and mice and compared with the activities previously found in peripheral lymphocytes. 2. With all species, except horse, the activity of ADA (per 10(6) cells) was higher in thymocytes than in lymphocytes. Activity of ADA was highest in splenocytes of pig and sheep. Activity of ADA was lowest in all lymphoid cells of the horse and only about 10% of the activity in human splenocytes and lymphocytes. 3. With all species, except horse, the activity of PNP was lower in thymocytes than in lymphocytes. Activity of PNP was highest in human lymphocytes and lowest in ovine thymocytes. 4. Activity of AK is comparable in thymocytes of all species and always lower than the ADA activity. In splenocytes of man, horse and pig the activity of AK is comparable to that in thymocytes. 5. Activity of deoxyguanosine kinase was lowest in rat thymocytes and highest in those of man. 6. When enzyme activities are expressed per milligram of protein, the differences between thymocytes and lymphocytes are less pronounced. 7. Activity of PRPP synthetase per 10(6) cells was comparable in thymocytes, splenocytes and lymphocytes of the same species and between the various species. 8. The concentration of PRPP was lowest in ovine thymocytes and higher in splenocytes than in thymocytes of the same species, except man.


Expression of vascular endothelial growth factor (VEGF) in various compartments of the human hair follicle.
Hair follicle vascularization appears to be closely related to the processes involved in hair cycle regulation, in which growth factors, cytokines and other bioactive molecules are involved. In particular, vascular endothelial growth factor (VEGF), essential for angiogenesis and vascular permeability, may be responsible for maintaining proper vasculature around the hair follicle during the anagen growth phase. The aim of our study was to compare the in vitro angiogenic capacity, i.e. the steady-state expression of the VEGF gene, of different cultured cell types derived from normal human hair follicles, corresponding to different follicular compartments. Human dermal papilla cells (DPC), fibrous sheath fibroblasts, dermal fibroblasts, and follicular and interfollicular keratinocytes were cultured and studied in vitro for VEGF expression at the mRNA level using RT-PCR, and for VEGF protein synthesis by radioimmunoprecipitation and immunocytochemistry. In vivo examination for VEGF expression in human terminal hair follicles was performed using immunohistochemical methods. In the present report the expression of four different VEGF molecular isoforms, differing in their angiogenic capacity, are described in different cultured follicular cell types for the first time. Cultured follicular cells strongly expressed mRNA of four VEGF molecular species identified as the 121-, 145-, 165- and 189-amino acid splice variants, the most prominent being the 121-amino acid molecule. DPC, and also other mesenchymal cells such as fibrous sheath fibroblasts and dermal fibroblasts, in vivo and in vitro strongly expressed VEGF mRNA and synthesized a 46-kDa VEGF protein, whereas follicular and interfollicular keratinocytes in vitro expressed lower levels of VEGF mRNA and proteins than mesenchymal cells. As the highest expression of VEGF was found in DPC, we suggest that DPC are mainly responsible for angiogenic processes possibly related to the human hair cycle.


Double-label two-dimensional electrophoresis of serum and plasma proteins from patients with multiple sclerosis.
A double-label two-dimensional electrophoretic procedure has been used to search for abnormal proteins in the serum and plasma of patients with definite multiple sclerosis. The procedure possesses high resolving power and is particularly valuable in comparative studies of complex mixtures of proteins since differences due to gel-to-gel variations in protein mobilities are eliminated. Proteins present in serum and plasma at a concentration of 5-10 micrograms/ml are detected routinely. No consistent differences were observed between patients with multiple sclerosis and normal subjects in comparisons using pooled or individual specimens of serum or plasma. The absence of consistent differences in serum and plasma proteins between normal subjects and MS patients applied even when the sensitivity of the procedure was increased several-fold and when the possibly obscuring effect of albumin in the electrophoretic gels was eliminated. To our knowledge, this study combines the most extensive and sensitive search for consistent abnormalities in serum and plasma proteins in multiple sclerosis sera thus far reported.


Biochemical Markers of Bone Fragility in Patients with Diabetes. A Narrative Review by the IOF and the ECTS.
The risk of fragility fractures is increased in both type 1 and type 2 diabetes. Numerous biochemical markers reflecting bone and/or glucose metabolism have been evaluated in this context. This review summarizes current data on biochemical markers in relation to bone fragility and fracture risk in diabetes. Literature review by a group of experts from the International Osteoporosis Foundation (IOF) and European Calcified Tissue Society (ECTS) focusing on biochemical markers, diabetes, diabetes treatments and bone in adults. Although bone resorption and bone formation markers are low and poorly predictive of fracture risk in diabetes, osteoporosis drugs seem to change bone turnover markers in diabetics similarly to non-diabetics, with similar reductions in fracture risk. Several other biochemical markers related to bone and glucose metabolism have been correlated with BMD and/or fracture risk in diabetes, including osteocyte-related markers such as sclerostin, HbA1c and advanced glycation end products (AGEs), inflammatory markers and adipokines, as well as IGF-1 and calciotropic hormones. Several biochemical markers and hormonal levels related to bone and/or glucose metabolism have been associated with skeletal parameters in diabetes. Currently, only HbA1c levels seem to provide a reliable estimate of fracture risk, while bone turnover markers could be used to monitor the effects of anti-osteoporosis therapy.


Stomatal closure induced by hydrogen-rich water is dependent on GPA1 in Arabidopsis thaliana.
Hydrogen (H2) is a new signaling molecule that regulates stomatal closure via stimulating the generation of reactive oxygen species (ROS) and nitric oxide (NO) in Arabidopsis thaliana. GPA1 is the sole heterotrimeric G protein canonical α subunit found in Arabidopsis genome and functions in stomatal closure. Here, we estimated a possible role of Arabidopsis GPA1 in hydrogen-rich water (HRW)-induced stomatal closure. Our data indicated that HRW induced significant stomatal closure as well as the generation of ROS and NO in the Col-0 guard cells. However, the production of ROS and NO and stomatal closure induced by HRW were absent in the gpa1-4 mutant lacking the expression of AtGPA1. By contrast, overexpression of AtGPA1 in gpa1-4 (AtGPA1-HA/gpa1-4) restored stomatal closure and the generation of NO and ROS in the presence of HRW. Taken together, our results suggest that GPA1 is necessary for HRW-induced stomatal closure in Arabidopsis.


A calorimetric method to assess endogenous metabolism and its application to the study of bovine sperm.
Calorimetry was used to assess the importance of endogenous metabolism towards total ATP synthesis in bovine sperm in the presence of extracellular glucose. Sperm were incubated in the calorimeter with D-[U-14C]glucose without or with electron transport inhibitors, rotenone and antimycin A. Steady-state heat production during the incubations was measured for 30 min, the incubations were terminated, and the cell suspensions removed for analysis of radioactive glucose and its metabolic end-products. Heat production (mean +/- S.E.) associated with the metabolism of glucose was calculated, from enthalpies of formation of glucose and its end-products, as -412 +/- 34 mJ/h/10(8) cells in control incubations and -263 +/- 18 mJ/h/10(8) cells in the incubations with electron transport inhibitors. Measured heat production was -455 +/- 36 and =263 +/- 17 mJ/h/10(8) cells, respectively. Thus, heat production by endogenous pathways, the difference between measured total heat production and calculated exogenous heat production, was -43 +/- 14 mJ/h/10(8) cells for control cells and about -6 mJ/h/10(8) cells for inhibited cells. The ratio of heat produced per mol of ATP synthesized is similar for all ATP-producing pathways. Therefore, about 10% of total ATP synthesis in control cells and less than 2% in inhibited cells is provided by endogenous pathways when extracellular glucose is present.


Resistance risk assessment for Fusarium graminearum to pydiflumetofen, a new succinate dehydrogenase inhibitor.
Pydiflumetofen is a new generation succinate dehydrogenase inhibitor currently undergoing the process of registration in China for the control of Fusarium head blight in wheat. A resistance risk assessment of Fusarium graminearum to pydiflumetofen was undertaken in this study. A total of 75 pydiflumetofen-resistant mutants were generated through spontaneous selection and displayed high resistance with an average resistance factor (RF) value of 78. Four mutants were generated through UV mutagenesis and displayed very high resistance with an RF value >1000. The sequence analysis results for Sdh genes and fitness studies revealed the existence of four types of mutations. In particular, 32 spontaneous selection mutants (SP mutants) had an arginine (R) to histidine (H) transition at position 86 in FGSdhC, resulting in seriously reduced fitness. Seven SP mutants had an R to cysteine (C) transition at position 86 in FGSdhC, resulting in reduced fitness. Thirty-six SP mutants had an alanine (A) to valine (V) transition at position 83 in FGSdhC and had no fitness penalties. The efficacy of pydiflumetofen towards a mutant carrying A83V in FGSdhC in vivo was significantly decreased at 42.7%. Four UV mutants had no mutations on all Sdh genes and no fitness penalties. Cross-resistance among boscalid, fluopyram and pydiflumetofen was observed. Sdhc mutations were found and other target site resistance may be present in laboratory PR mutants of F. graminearum. An overall moderate risk of resistance development in F. graminearum was recommended for pydiflumetofen. © 2019 Society of Chemical Industry.


Leg-Length Change After Unilateral Unicompartmental Knee Arthroplasty in Varus Knee and Its Clinical Implications.
To explore the magnitude of leg-length change after the unilateral index unicompartmental knee arthroplasty (UKA) in varus knee and its influence on clinical outcomes. A total of 114 patients with bilateral knee osteoarthritis who underwent unilateral UKA from June 2015 to June 2017 were included and followed up for at least 2 years. The leg length and hip-knee angle were measured on full-length standing films before and after the surgery. Flexion contracture was evaluated using a goniometer with the patient in the standing position preoperatively and postoperatively. Hospital for Special Surgery scores, perceived leg-length discrepancy (pLLD), the occurrence, and the time interval of subsequent contralateral knee arthroplasty were recorded and analyzed. The average leg length increased after UKA was 9.39 ± 11.24 mm (range -21.00 to 33.79 mm), and 90 (78.9%) patients showed an increase in the leg length. 35 patients had LLD (defined as ≥10 mm), and 25 presented pLLD preoperatively; 25 patients had LLD, and 45 were suspected with pLLD postoperatively. At the last follow-up, 26 patients underwent subsequent contralateral knee arthroplasty. Postoperative LLD and pLLD were not associated with Hospital for Special Surgery scores of UKA but associated with subsequent contralateral knee arthroplasty. LLD and pLLD were common in patients both before and after UKA. Most patients showed leg lengthening after UKA. Postoperative LLD and pLLD were not associated with functional scores but associated with a subsequent contralateral knee arthroplasty.


A review of current status of cell-based therapies for aortic aneurysms.
An aortic aneurysm (AA) is defined as focal aortic dilation that occurs mainly with older age and with chronic inflammation associated with atherosclerosis. The aneurysmal wall is a complex inflammatory environment characterized by endothelial dysfunction, macrophage activation, vascular smooth muscle cell (VSMC) apoptosis, and the production of proinflammatory molecules and matrix metalloproteases (MMPs) secreted by infiltrated inflammatory cells such as macrophages, T and B cells, dendritic cells, neutrophils, mast cells, and natural killer cells. To date, a considerable number of studies have been conducted on stem cell research, and growing evidence indicates that inflammation and tissue repair can be controlled through the functions of stem/progenitor cells. This review summarizes current cell-based therapies for AA, involving mesenchymal stem cells, VSMCs, multilineage-differentiating stress-enduring cells, and anti-inflammatory M2 macrophages. These cells produce beneficial outcomes in AA treatment by modulating the inflammatory environment, including decreasing the activity of proinflammatory molecules and MMPs, increasing anti-inflammatory molecules, modulating VSMC phenotypes, and preserving elastin. This article also describes detailed studies on pathophysiological mechanisms and the current progress of clinical trials.


Rapid implementation of a mobile prone team during the COVID-19 pandemic.
The coronavirus disease 2019 (COVID-19) is associated with high rates of acute respiratory distress syndrome (ARDS). Prone positioning improves mortality in moderate-to-severe ARDS. Strategies to increase prone positioning under crisis conditions are needed. We describe the development of a mobile prone team during the height of the crisis in New York City and describe characteristics and outcomes of mechanically ventilated patients who received prone positioning between April 2, 2020 and April 30, 2020. Ninety patients underwent prone positioning for moderate-to-severe ARDS. Sixty-six patients (73.3%) were men, with a median age of 64 years (IQR 53-71), and the median PaO2:FiO2 ratio was 107 (IQR 85-140) prior to prone positioning. Patients required an average of 3 ± 2.2 prone sessions and the median time of each prone session was 19 h (IQR 17.5-20.75). By the end of the study period, proning was discontinued in sixty-seven (65.1%) cases due to clinical improvement, twenty (19.4%) cases due to lack of clinical improvement, six (5.8%) cases for clinical worsening, and ten (9.7%) cases due to a contraindication. The rapid development of a mobile prone team safely provided prone positioning to a large number of COVID-19 patients with moderate-to-severe ARDS.


Induction of N-acetylmannosamine catabolic pathway in yeast.
N-Acetylmannosamine kinase activity is absent from yeast cells grown on N-acetylmannosamine. However, other enzymes of the catabolic pathway, namely, N-acetylmannosamine-2-epimerase, N-acetylglucosamine kinase and glucosamine-6-phosphate deaminase are induced. In addition, a high affinity uptake system (permease) for the uptake of N-acetylglucosamine is synthesized under these conditions. The presence of either N-acetylmannosamine or N-acetylglucosamine as inducer is essential for the induced synthesis of these enzymes. The enzyme synthesis stops and their concentration in the cells declines rapidly as soon as inducer is removed from the medium. N-Acetyl-D-galactosamine can also induce all these enzymes except for N-acetylmannosamine-2-epimerase, suggesting the convergence of catabolic pathways for both the aminosugars at N-acetyl-D-glycosamine. Experiments with inhibitors of macromolecule synthesis suggest that the snythesis of RNA and protein is necessary for the induction of these cyzymes whereas the synthesis of DNA is not.


Invasive hemodynamic characteristics of low gradient severe aortic stenosis despite preserved ejection fraction.
The study sought to compare echocardiographic with invasive hemodynamic data in patients with "paradoxic" aortic stenosis and in patients with conventionally defined severe aortic stenosis. Controversy exists whether low gradient severe aortic stenosis despite preserved ejection fraction ("paradoxic" aortic stenosis; aortic valve area <1 cm(2), mean gradient <40 mm Hg, ejection fraction >50%), which has been mainly diagnosed by echocardiography (echo), may be largely due to mistakes in echocardiographic measurements. We compared echocardiographic and invasive hemodynamic data from 58 patients (43% male, mean age 77 ± 5 years) with "paradoxic" aortic stenosis. Data of 22 patients (45% male, mean age 73 ± 7 years) with conventionally defined severe aortic stenosis area (aortic valve area ≤1 cm(2), mean gradient >40 mm Hg, ejection fraction ≥50%) were also analyzed. In patients with "paradoxic" aortic stenosis, orifice area by echo (0.80 ± 0.15 cm(2)) and catheterization showed modest agreement, whether stroke volume was measured by oxymetry (0.69 ± 0.16 cm(2), bias 0.14 ± 0.17 cm(2)), or by thermodilution (0.85 ± 0.19 cm(2), bias -0.03 ± 0.19 cm(2)). Mean systolic gradients were very similar (32 ± 7 mm Hg vs. 31 ± 6 mm Hg; bias -0.08 ± 7.8 mm Hg). In comparison, in patients with conventionally defined severe aortic stenosis, orifice area by echo was 0.72 ± 0.17 cm(2) and by catheterization 0.51 ± 0.15 cm(2) (oxymetry) and 0.68 ± 0.21 cm(2) (thermodilution), respectively, and mean systolic gradient 51 ± 10 mm Hg and 55 ± 8 mm Hg, respectively. Ejection fractions did not differ significantly in both groups. Ascending aortic diameter was significantly smaller in the "paradoxic" aortic stenosis group than in patients with conventionally defined severe aortic stenosis (28 ± 5 mm vs. 31 ± 5 mm), and energy loss index was significantly larger (0.51 ± 0.12 cm(2)/m(2) vs. 0.42 ± 0.09 cm(2)/m(2), respectively). Heart rate and mean blood pressure during echo and catheterization were not significantly different. Occurrence of low gradient severe aortic stenosis despite preserved ejection fraction was confirmed by invasive hemodynamics and was not the result of a systematic bias in the echo calculation of aortic orifice area.


Dipeptide-polysaccharides hydrogels through co-assembly.
Self-assembling dipeptide hydrogels are attracting attention in food, materials, and biomedicine. However, there are still limitations such as weak hydrogel properties. Herein, we introduced two types of polysaccharides (Arabic gum and citrus pectin) into an alkyl-chain modified dipeptide (C13-tryptophan-tyrosine (C13-WY)) to generate co-assembled C13-WY-arabic gum and C13-WY-pectin hydrogels. The co-assembled hydrogels exhibited enhanced mechanical properties and stability. The G' value of C13-WY-arabic gum and C13-WY-pectin hydrogels was 3 and 10 times larger than that of C13-WY hydrogel, respectively. The addition of Arabic gum and citrus pectin led to the co-assembly and molecular rearrangement. Moreover, co-assembled hydrogels showed more β-sheet structure and hydrogen bonds. Importantly, the self-/co-assembled hydrogels showed low cytotoxicity. We utilized these hydrogels for the encapsulation of docetaxel and they showed a high embedding rate and slow-release. Our findings provide a novel strategy for the development of stable supramolecular peptide hydrogels with good biocompatibility through simple co-assembly.