Impact of papillary muscle approximation on mitral valve configuration in the surgical correction of ischemic mitral regurgitation.
Efficacy of papillary muscle approximation (PMA) has not been well defined. Mitral valve configuration was assessed using echocardiography before and 1 week after the surgery in 27 consecutive patients undergoing surgical correction of ischemic MR. Comparisons were made between patients undergoing restrictive mitral annuloplasty (RMAP) alone (n = 13, RMAP group) and those undergoing PMA in addition to RMAP (n = 14, PMA group). In the RMAP group, the annular diameter was reduced by 43% after surgery, and annular reduction was greater in the posterior portion than in the anterior. Consequently, the tethering angle of the posterior leaflet (PL) increased after surgery. In the PMA group, the annular diameter was reduced by 33%, and annular reduction was greater in the posterior. In this group also, the tethering angle of PL increased significantly after surgery, although the degree of augmentation was lower compared with that in the RMAP group. The addition of PMA to RMAP could attenuate but do not eliminate the tethering augmentation of PL.


Estimated Life Expectancy and Income of Patients With Sickle Cell Disease Compared With Those Without Sickle Cell Disease.
Individuals with sickle cell disease (SCD) have reduced life expectancy; however, there are limited data available on lifetime income in patients with SCD. To estimate life expectancy, quality-adjusted life expectancy, and income differences between a US cohort of patients with SCD and an age-, sex-, and race/ethnicity-matched cohort without SCD. Cohort simulation modeling was used to (1) build a prevalent SCD cohort and a matched non-SCD cohort, (2) identify utility weights for quality-adjusted life expectancy, (3) calculate average expected annual personal income, and (4) model life expectancy, quality-adjusted life expectancy, and lifetime incomes for SCD and matched non-SCD cohorts. Data sources included the Centers for Disease Control and Prevention, National Newborn Screening Information System, and published literature. The target population was individuals with SCD, the time horizon was lifetime, and the perspective was societal. Model data were collected from November 29, 2017, to March 21, 2018, and the analysis was performed from April 28 to December 3, 2018. Life expectancy, quality-adjusted life expectancy, and projected lifetime income. The estimated prevalent population for the SCD cohort was 87 328 (95% uncertainty interval, 79 344-101 398); 998 were male and 952 were female. Projected life expectancy for the SCD cohort was 54 years vs 76 years for the matched non-SCD cohort; quality-adjusted life expectancy was 33 years vs 67 years, respectively. Projected lifetime income was $1 227 000 for an individual with SCD and $1 922 000 for a matched individual without SCD, reflecting a lost income of $695 000 owing to the 22-year difference in life expectancy. One study limitation is that the higher estimates of life expectancy yielded conservative estimates of lost life-years and income. The analysis only considered the value of lost personal income owing to premature mortality and did not consider direct medical costs or other societal costs associated with excess morbidity (eg, lost workdays for disability, time spent in the hospital). The model was most sensitive to changes in income levels and mortality rates. In this simulated cohort modeling study, SCD had societal consequences beyond medical costs in terms of reduced life expectancy, quality-adjusted life expectancy, and lifetime earnings. These results underscore the need for disease-modifying therapies to improve the underlying morbidity and mortality associated with SCD.


The ivory vertebra: an approach to investigation and management based on two case studies.
Case report. To report and discuss the natural evolution of fortuitously found solitary radiodense or "ivory" vertebrae in two asymptomatic patients; to review the existing literature concerning ivory vertebrae; and to provide a practical guide for the diagnostic and management approach to the fortuitous finding of ivory vertebrae in asymptomatic patients. The asymptomatic and apparently idiopathic ivory vertebra is often a very problematic clinical situation. Previous studies have hypothesized that although several etiologies have been known to be responsible for producing ivory vertebrae, the most likely etiology, particularly for so-called "idiopathic" ivory vertebrae, is early and asymptomatic Paget's disease of bone. Two patients, each with an incidentally discovered ivory vertebra, were followed clinically over a period of 13 and 10 years, respectively. During this time the patients underwent a multitude of investigations in an attempt to identify the etiology of the ivory vertebra. After having eliminated ominous etiologies, the authors opted for a conservative approach to management (observation) so as to have a long-term follow-up of the patients and also attempt to determine the natural history of idiopathic solitary ivory vertebrae. Despite the extensive workups, no etiology was ever found for either patient because the tests showed normal results for extended periods of time. Whereas in one patient Paget's disease of bone was suspected, no definitive confirmation for the presence of Paget's disease could be obtained, even on bone biopsy. Both patients remained entirely asymptomatic with respect to the ivory vertebra over the entire follow-up period. Based on the observations from the present study as well as a review of the literature on the subject, a decision-making algorithm is put forth for the investigative approach as well as for the subsequent follow-up and management of patients with idiopathic and asymptomatic ivory vertebrae whereby, after baseline screening tests eliminate ominous pathology, observation and periodic clinical reassessment are advised until symptoms develop or until there are radiographic changes in the appearance of the ivory vertebra.


Establishing treatment benchmarks for mammography-screened breast cancer population based on a review of evidence-based clinical guidelines.
No benchmarks exist in the screened breast cancer population to establish the optimal proportions of newly detected cancer patients who should receive the ideal treatment. The aim of the study was to estimate the optimal proportion of cases diagnosed in a breast-screening program who should receive treatment according to evidence-based cancer treatment guidelines and to compare these optimal rates with actual treatment rates. METHOD.: Optimal surgery, radiotherapy, chemotherapy, and hormone therapy utilization trees were constructed based on indications from evidence-based treatment guidelines. The proportions with clinical attributes that indicated a possible benefit from a particular treatment were obtained from epidemiologic data from BreastScreen Victoria. The optimal proportions of screen-detected breast cancer patients who should receive various therapies were then calculated using TreeAge software and compared with the actual proportions obtained from the epidemiologic data. According to the best available evidence, the proportion of screen-detected breast cancer patients who have attributes suitable for various treatments are: breast-conserving surgery (BCS) 85%, mastectomy 15%, radiotherapy 87%, chemotherapy 34%, and hormonal therapy 68%. The actual BCS utilization rate in Victoria was similar to the optimal rate (79% vs 85%), whereas there appeared to be underuse of radiotherapy (62% vs 87%), chemotherapy (19% vs 34%), and hormonal therapy (49% vs 68%) when compared with guideline recommendations. This research provided optimal treatment utilization rates for screen-detected breast cancer and a comparison of best practice evidence and actual treatment. The results showed comparable rates for surgery but suggested underutilization of radiotherapy, chemotherapy, and hormone therapy.


Arthroscopically Assisted Tape Augmentation for Anterior Talofibular Ligament Repair.
In this Technical Note, we describe arthroscopically assisted tape augmentation of a modified Broström repair for chronic lateral ankle instability. Specifically, this technique involves talar anchor placement under direct arthroscopic visualization combined with a minimally invasive approach for anatomic anterior talofibular ligament repair and FiberTape (Arthrex, Naples, FL) augmentation. The primary advantage of our technique compared with open InternalBrace (Arthrex) techniques is that only a 2-cm incision is made and no subcutaneous suture passing and knot tying are required, which bear the danger of superficial peroneal nerve damage. In addition, the risk of nonanatomic anchor placement is diminished owing to direct arthroscopic visualization and preparation of the anterior talofibular ligament remnants.


Estimating the Total Annual Direct Cost of Providing Sexually Transmitted Infection and HIV Testing and Counseling for Men Who Have Sex With Men in the United States.
The Centers for Disease Control and Prevention recommends annual sexually transmitted infection (STI) and HIV testing and counseling for men who have sex with men (MSM) in the United States. We estimated the annual total direct medical cost of providing recommended STI and HIV testing and counseling services for MSM in the United States. We included costs for 9 STI (including anatomic site-specific) tests recommended by the Centers for Disease Control and Prevention (HIV, syphilis, gonorrhea, chlamydia, hepatitis B viral infection, and herpes simplex virus type 2), office visits, and counseling. We included nongenital tests for MSM with exposure at nongenital sites. All cost data were obtained from the 2012 MarketScan outpatient claims database. Men were defined as MSM if they had a male sex partner within the last 12 months, which was estimated at 2.9% (2.6%-3.2%) of the male population in a 2012 study. All costs were updated to 2014 US dollars. The estimated average costs were as follows: HIV ($18 [$9-$27]), hepatitis B viral infection ($23 [$12-$35]), syphilis ($8 [$4-$11]), gonorrhea and chlamydia ($45 [$22-$67]) per anatomic site), herpes simplex virus type 2 ($27 [$14-$41]), office visit ($100 [$50-$149]), and counseling ($29 [$15-$44]). We estimated that the total annual direct cost of a universal STI and HIV testing and counseling program was $1.1 billion ($473 million-$1.7 billion) for all MSM and $756 (range, $338-$1.2 billion) when excluding office visit cost. These estimates provide the potential costs associated with universal STI and HIV testing and counseling for MSM in the United States. This information may be useful in future cost and/or cost-effectiveness analyses that can be used to evaluate STI and HIV prevention efforts.


Structures and Properties of trans-1,3,3,3-Tetrafluoro- propene (HFO-1234ze) and 2,3,3,3-Tetrafluoropropene (HFO-1234yf) Refrigerants.
The refrigerant trans-1,3,3,3-tetrafluoropropene (HFO-1234ze) is used as a replacement for former cooling agents that have been phased-out due to their global warming potential or ozone depleting potential. Although it is used on a large scale, only a few vibrational data and no structural data of HFO-1234ze are known. We report structure determinations based on low-temperature single-crystal X-ray diffraction data as well as gas-phase diffraction data of HFO-1234ze and HFO-1234yf (2,3,3,3-tetrafluoropropene). Furthermore, vibrational spectra of HFO-1234ze in all phases are described. The results are discussed together with quantum-chemical calculations on the PBE0/cc-pVTZ level of theory. Combustion experiments of HFO-1234ze show carbonyl difluoride, carbon dioxide and hydrogen fluoride to be the main combustion products.


Optimizing initial therapy in DLBCL.
Diffuse large B-cell lymphoma (DLBCL) is a group of lymphomas comprising heterogeneous molecular and biological subtypes, reflected in a broad range of clinical outcomes. With the standard R-CHOP regimen of cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab administered every 21 days, the treatment failure rate remains unacceptably high in certain DLBCL subsets. Here we review possible avenues for optimizing initial therapy. The role of functional imaging and biological features, such as double-hit lymphomas, defined by the dual translocation of MYC and BCL2, and dual protein-expresser lymphomas, defined by the overexpression of MYC and BCL2, activated B-cell (ABC)-like DLBCL, to better define these high-risk patient subsets, and their use to guide and personalize treatment decisions are discussed. Secondly, the implications of varying dose-intensification of the various agents administered, and the link to imaging are reviewed. Thirdly, the results of the addition of novel drugs to standard R-CHOP will be analyzed, when added at induction or in maintenance. Finally, with CNS relapse in DLBCL representing a major and devastating unmet medical need, an overview and future directions for CNS prophylaxis is presented.


Interacting haplotypes at the NPAS3 locus alter risk of schizophrenia and bipolar disorder.
The neuronal PAS domain 3 (NPAS3) gene encodes a neuronal transcription factor that is implicated in psychiatric disorders by the identification of a human chromosomal translocation associated with schizophrenia and a mouse knockout model with behavioural and hippocampal neurogenesis defects. To determine its contribution to the risk of psychiatric illness in the general population, we genotyped 70 single-nucleotide polymorphisms across the NPAS3 gene in 368 individuals with bipolar disorder, 386 individuals with schizophrenia and 455 controls. Modestly significant single-marker and global and individual haplotypes were identified in four discrete regions of the gene. The presence of both risk and protective haplotypes at each of these four regions indicated locus and allelic heterogeneity within NPAS3 and suggested a model whereby interactions between variants across the gene might contribute to susceptibility to illness. This was supported by predicting the most likely haplotype for each individual at each associated region and then calculating an NPAS3-mediated 'net genetic load' value. This value differed significantly from controls for both bipolar disorder (P=0.0000010) and schizophrenia (P=0.0000012). Logistic regression analysis also confirmed the combinatorial action of the four associated regions on disease risk. In addition, sensitivity/specificity plots showed that the extremes of the genetic loading distribution possess the greatest predictive power-a feature suggesting multiplicative allele interaction. These data add to recent evidence that the combinatorial analysis of a number of relatively small effect size haplotypes may have significant power to predict an individual's risk of a complex genetic disorder such as psychiatric illness.


Incidentalomas during imaging for primary hyperparathyroidism--incidence and clinical outcomes.
Imaging for pre-operative localisation of parathyroid glands in primary hyperparathyroidism is now routine. This has led to the detection of incidental lesions (incidentalomas) in other organs, the nature of which is not well characterised. The aim of this study was to determine the incidence, characteristics and outcomes in patients who had incidental findings on parathyroid imaging. Records of patients who underwent imaging for primary hyperparathyroidism over 2 years were reviewed to identify incidental lesions detected on parathyroid imaging. Patients with persistent or renal hyperparathyroidism were excluded. Details on the management of detected incidentalomas were obtained from patient records. Incidentalomas were identified in 17 of 170 patients (10%) undergoing parathyroid imaging. Incidentalomas included thyroid (n = 11), breast (n = 3), lateral compartment of the neck (n = 1), lung (n = 1) and clavicle (n = 1). However, no disease of clinical significance needing treatment was detected on further investigation. Although a significant proportion of patients undergoing parathyroid imaging had incidental lesions detected, these seem to be of little clinical significance. The morbidity and cost of further interventions on these incidentalomas need to be weighed against the benefits of routine imaging in improving outcomes of first-time surgery in patients with primary hyperparathyroidism.


Binding of the tautomeric forms of isoniazid-NAD adducts to the active site of the Mycobacterium tuberculosis enoyl-ACP reductase (InhA): a theoretical approach.
The front-line antituberculosis drug isoniazid (INH) inhibits InhA, the NADH-dependent fatty acid biosynthesis enoyl ACP-reductase from Mycobacterium tuberculosis, via formation of covalent adducts with NAD (INH-NAD adducts). While ring tautomers were found the main species formed in solution, only the 4S chain INH-NAD tautomer was evidenced in the crystallized InhA:INH-NAD complex. In this study we attempted to explore the modes of interaction and energy binding of the different isomers placed in the active site of InhA with the help of various molecular modelling techniques. Ligand and enzyme models were generated with the help of the Vega ZZ program package. Resulting ligands were then docked into the InhA active site individually using computational automated docking package AUTODOCK 3.0.5. The more relevant docked conformations were then used to compute the interaction energy between the ligands and the InhA cavity. The AM1 Hamiltonian and the QM/MM ONIOM methodologies were used and the results compared. The various tautomers were found docked in almost the same place where INH-NAD was present as predicted by earlier X-ray crystallographic studies. However, some changes of ligand conformation and of the interactions ligand-protein were evidenced. The lower binding energy was observed for the 4S chain adduct that probably represents the effective active form of the INH-NAD adducts, as compared to the 4R epimer. The two 4S,7R and 4R,7S ring tautomers show intermediate and similar binding energies contrasting with their different experimental inhibitory potency on InhA. As a possible explanation based on calculated conformations, we formulated the hypothesis of an initial binding of the two ring tautomers to InhA followed by opening of only the ring hemiamidal 4S,7R tautomer (possibly catalyzed by Tyr158 phenolate basic group) to give the 4S chain INH-NAD tight-binding inhibitor. The predictions of ligand-protein interactions at the molecular level can be of primary importance in elucidating the mechanisms of action of isoniazid and InhA-related resistances, in identifying the effective mycobactericidal entities and, in further step, in the design of a new generation of antitubercular drugs.


Toward understanding of evolutionary constraints: experimental and theoretical approaches.
Although organisms have diversified remarkably through evolution, they do not exhibit unlimited variability. During evolution, the phenotypic changes do not occur at random; instead, they are directional and restricted by the constraints imposed on them. Despite the perceived importance of characterizing the unevenness of these changes, studies on evolutionary constraints have been primarily qualitative in nature. In this review, we focus on the recent studies of evolutionary constraints, which are based on the quantification of high-dimensional phenotypic and genotypic data. Furthermore, we present a theoretical analysis that enables us to predict evolutionary constraints on the basis of phenotypic fluctuation, modeled on the fluctuation-response relationship in statistical physics. The review lays emphasis on the tight interactions between experimental and theoretical analyses in evolutionary biology that will contribute to a better understanding of evolutionary constraints.


A transparent over-tube for endoscopic injection sclerotherapy and results in patients with esophageal varices.
This report describes our data regarding repeated injection sclerotherapy using a newly designed over-tube. We treated 17 consecutive patients with esophageal varices, (3 acute, 6 elective and 8 prophylactic). An intravariceal injection of 5 per cent ethanolamine oleate was administered, using a newly designed transparent over-tube containing a second lumen for a flexible injection needle. This over-tube provides an easier, safer, shorter-in-time method of sclerosing esophageal varices. One of the 17 patients died as a result of liver failure associated with advanced cirrhosis and a concomitant hepatoma. Eradication of esophageal varices was attained in the remaining 16 patients, after an average of 5.0 injections over an average period of 5.8 weeks (range: 3-7 injections during 3-11 weeks). No complications, such as esophageal perforation or aspiration pneumonia were encountered. Recurrent variceal bleeding has not occurred during the 9 months follow-up.


Complete mitochondrial genome of the Amur stickleback Pungitius sinensis (Gasterosteiformes, Gasterosteidae).
The complete mitochondrial genome was sequenced from the Amur stickleback Pungitius sinensis. The genome sequence was 16,581 bp in size, and the gene order and contents were identical with those of previously reported fish mitochondrial genomes. Of 13 protein-coding genes (PCGs), four genes (ND2, CO2, ND4, Cytb) had incomplete stop codons. The base composition of P. sinensis showed anti-G bias (9.53%) on the third position of PCGs.


Biomarker changes as surrogate endpoints in early-phase trials in heart failure with reduced ejection fraction.
No biomarker has achieved widespread acceptance as a surrogate endpoint for early-phase heart failure (HF) trials. We assessed whether changes over time in a panel of plasma biomarkers were associated with subsequent morbidity/mortality in HF with reduced ejection fraction (HFrEF). In 1040 patients with HFrEF from the BIOSTAT-CHF cohort, we investigated the associations between changes in the plasma concentrations of 30 biomarkers, before (baseline) and after (9 months) attempted optimization of guideline-recommended therapy, on top of the BIOSTAT risk score and the subsequent risk of HF hospitalization/all-cause mortality using Cox regression models. C-statistics were calculated to assess discriminatory power of biomarker changes/month-nine assessment. Changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and WAP four-disulphide core domain protein HE4 (WAP-4C) were the only independent predictors of the outcome after adjusting for their baseline plasma concentration, 28 other biomarkers (both baseline and changes), and BIOSTAT risk score at baseline. When adjusting for month-nine rather than baseline biomarkers concentrations, only changes in NT-proBNP were independently associated with the outcome. The C-statistic of the model including the BIOSTAT risk score and NT-proBNP increased by 4% when changes were considered on top of baseline concentrations and by 1% when changes in NT-proBNP were considered on top of its month-nine concentrations and the BIOSTAT risk score. Among 30 relevant biomarkers, a change over time was significantly and independently associated with HF hospitalization/all-cause death only for NT-proBNP. Changes over time were modestly more prognostic than baseline or end-values alone. Changes in biomarkers should be further explored as potential surrogate endpoints in early phase HF trials.


COVID-19 Vaccine Hesitancy in Middle-Aged and Older Adults in India: A Mixed-Methods Study.
Vaccine hesitancy is a significant threat to public health efforts to stop the negative impacts of the COVID-19 pandemic. In India, it is critical to attain high vaccination rates to prevent overload in the healthcare system. Older adults play a central role in families' decision-making, but there is a lack of research on middle-aged and older adults' vaccine perceptions in India in general, and about their concerns about COVID-19 vaccinations. This study aimed to explore which factors affect COVID-19 vaccine hesitancy in middle-aged and older adults in India and what factors can reduce their vaccine hesitancy and increase its uptake. A mixed-method sequential design was employed to conduct the study. Convenience sampling was used to recruit participants by sending an online invitation. For phase one of the study, a quantitative survey with 34 questions was distributed through WhatsApp. For phase two of the study, qualitative one-on-one interviews were conducted with those participants who completed the survey and agreed to participate in this next phase. In total, 65 individuals responded to the online survey and 10 participated in semi-structured interviews. The participants were residing in India and their age range was from 40 to 89 years. Analysis of the data identified that although the majority of participants supported the vaccine, the main reasons for vaccine hesitancy included uncertainty about the effectiveness of the vaccine, fear of side effects, unclear and insufficient information about the vaccines and altered risk perception. This study also showed that those who felt that the consequences of COVID-19 were mild were also more likely to be vaccine-hesitant. While the results of the study showed that most of the participants supported the COVID-19 vaccines, they expressed uncertainty regarding their effectiveness. The safety and effectiveness of the vaccines were found to be prime contributing factors to vaccine hesitancy in this sample. The findings from this pilot study can be used to develop a larger, more comprehensive study on vaccine hesitancy among middle-aged and older adults in India, which would provide more insights into strategies that can be employed to promote vaccinations.


Dietary patterns and their association with cardiovascular risk factors in a population undergoing lifestyle changes: The Strong Heart Study.
Rates of cardiovascular disease (CVD) are disproportionately high in American Indians (AI), and changes in lifestyle may be responsible. It is not known whether diverse dietary patterns exist in this population and whether the patterns are associated with CVD risk factors. This article describes the relationships between dietary patterns and CVD risk factors in this high-risk population. Nutrition data were collected via food frequency questionnaire from 3438 Strong Heart Study (SHS) participants, ≥ age 15 y. All participants were members of 94 extended families. The final sample consisted of 3172 men and women. Diet patterns were ascertained using factor analysis with the principal component factoring method. We derived four predominant dietary patterns: Western, traditional AI/Mexican, healthy, and unhealthy. Participants following the Western pattern had higher LDL cholesterol (LDL-C) (p < 0.001), slightly higher systolic blood pressure (BP) (p < 0.001), lower HDL cholesterol (HDL-C) (p < 0.001), and slightly lower homeostasis model assessment estimates of insulin resistance (HOMA-IR) in the lowest vs. highest deciles of adherence to this pattern (p < 0.001). The traditional diet was associated with higher HDL-C (p < 0.001), but higher body mass index (BMI) (p < 0.001) and HOMA-IR (p < 0.001). Followers of the healthy pattern had lower systolic BP, LDL-C, BMI, and HOMA-IR in increasing deciles (p < 0.001). The unhealthy pattern was associated with higher LDL-C. Dietary patterns reflect the changing lifestyle of AI and several of the patterns are associated with CVD risk factors. Evolving methods of food preparation have made the traditional pattern less healthy.


Net clinical benefit of edoxaban versus no treatment in a 'real world' atrial fibrillation population: A modelling analysis based on a nationwide cohort study.
In non-valvular atrial fibrillation (AF), oral anticoagulation reduces the risk of thromboembolism such as stroke and systemic embolism (SSE), but increases the risk of major bleeding such as intracranial haemorrhage (ICH). The risk-benefit balance between SSE versus ICH can be expressed as the net clinical benefit (NCB); however, the risk of SSE and ICH varies according to clinical factors that can be assessed using CHADS2, CHA2DS2-VASc (both quantifying risk of stroke) and HAS-BLED (quantifying risk of major bleeding) scores, respectively. Using established modelling based on event rates for thromboembolism and haemorrhage in the Danish nationwide cohort study, we tested the hypothesis that edoxaban has a superior NCB compared with warfarin. In our overall model, compared to no treatment, warfarin had a NCB of 0.26 (95% CI 0.24,0.28) events prevented per 100 patient years, edoxaban 60 mg daily a NCB of 0.71 [0.69,0.76], and edoxaban 30 mg daily a NCB of 0.71 [0.0.68,0.73]. When compared to no treatment, both doses of edoxaban have superior NCB values than those of warfarin at all CHADS2 and CHA2DS2-VASc scores. At CHADS2 ≥2 and CHA2DS2-VASc ≥2, edoxaban 60 mg dose had a better NCB than the 30 mg dose or warfarin, when compared to no treatment. With HAS-BLED score ≥3, both doses of edoxaban had a positive NCB compared to warfarin, at CHADS2 or CHA2DS2-VASc ≥2. Our modelling study suggests that both 30 mg and 60 mg doses of edoxaban have a favourable NCB compared to warfarin, and the degree of benefit differs according to CHADS2, CHA2DS2-VASc and HAS-BLED scores. At CHA2DS2-VASc score ≥2, both edoxaban doses were superior to warfarin, but compared to no treatment, the 60 mg dose had a better NCB than the 30 mg dose or warfarin.


LiFePO4 nanoparticles enveloped in freestanding sandwich-like graphitized carbon sheets as enhanced remarkable lithium-ion battery cathode.
A novel nanostructure where LiFePO4 nanoparticles are enveloped in sandwich-like carbon sheets as an enhanced cathode in lithium-ion batteries has successfully been synthesized for the first time. Compared to previous carbon-based nanocomposites, the achieved sandwich-like LiFePO4 nanocomposites exhibit totally different architecture, in which LiFePO4 nanoparticles are tightly entrapped between two carbon layers, instead of being anchored on the carbon sheet surfaces. In other words, the achieved sandwich-like LiFePO4 nanocomposite carbon layers are actually freestanding and can be operated and separated from each other. This is a great breakthrough in the design and synthesis of carbon-based functional materials. The obtained sandwich-like LiFePO4 nanocomposites present excellent electrochemical performance, which is rationally ascribed to the superb and unique structure and architecture. Of particular note is that the freestanding sandwich-like LiFePO4 nanocomposites exhibit enhanced cyclability and rate capability. At a high current density of 0.1 A g(-1), a stable specific capacity of approximately 168.5 mAh g(-1) can be delivered over 1000 cycles, and when the charge-discharge rates increase to 0.6, 2, 5 and 10 A g(-1), the specific capacities still survive at 149, 129, 114 and 91 mAh g(-1), respectively. Meanwhile, the sandwiched nanocomposite demonstrates a significantly improved low-temperature electrochemical energy storage performance. With respect to the excellent Li storage performance, and facility and reliability of production, the freestanding sandwich-like LiFePO4 nanocomposites are reasonably believed to have a great potential for multiple electrochemical energy storage applications.


Giant cell arteritis: epidemiology, diagnosis, and management.
Giant cell arteritis (GCA), also called temporal arteritis, is a vasculitis that affects large and middle-sized blood vessels--with predisposition to the involvement of cranial arteries derived from the carotid artery--in individuals older than 50 years of age. Familial aggregation of GCA has been observed. Incidence of GCA is higher in white individuals than those of other ethnicities, particularly those of Scandinavian background. A temporal artery biopsy is the gold standard test for the diagnosis of GCA. Several imaging modalities, in particular ultrasonography, are useful in the diagnosis of GCA. Corticosteroids are the cornerstone of treatment in GCA. Alternative, steroid-sparing drugs, particularly methotrexate, should be considered in GCA patients with severe corticosteroid-related side effects and/or in those who require prolonged corticosteroid therapy due to relapses of the disease.


[Role of soft tissue in orthodontic diagnosis. 1].
The Authors propose a review of the soft-tissue cephalometric analysis, to show its diagnostic usefulness.


Simultaneous enhancement of nonylphenol biodegradation and short-chain fatty acids production in waste activated sludge under acidogenic conditions.
Nonylphenol (NP) biodegradation in waste activated sludge (WAS) under anaerobic conditions is usually slow, and no information on NP biodegradation under acidogenic conditions is currently available. In this study, the simultaneous enhancement of NP biodegradation and short-chain fatty acids (SCFAs) accumulation in a WAS fermentation system under acidogenic conditions was accomplished by controlling pH 10 and adding sodium lauryl sulfate (SLS). The biodegradation efficiency of NP was found to be 55.5% within 8 d under acidogenic conditions, much higher than that in the control (24.6%). Meanwhile, the concentration of SCFAs under the same conditions for NP biodegradation was increased from 2234 mg COD/L (control) to 4691 mg COD/L (at pH 10 with SLS). Mechanism study revealed that the abundances of both NP-degrading microorganisms and acidogenic bacteria increased under acidogenic conditions. Altering the enzymatic activity and the quantity of functional genes in the acidogenic fermentation system were beneficial to NP biodegradation and SCFAs accumulation. Furthermore, organic substrates available for uptake by NP-degrading and acidogenic bacteria, i.e. NP, protein and carbohydrate, were released from WAS under acidogenic conditions. More importantly, intermediate substrates involved in acidogenic fermentation were advantageous to the cometabolic biodegradation of NP.


Osteoporosis in the community: Sensitivity of self-reported estimates and medication use of those diagnosed with the condition.
To assess the sensitivity and specificity of self-reported osteoporosis compared with dual energy X-ray absorptiometry (DXA) defined osteoporosis, and to describe medication use among participants with the condition. Data were obtained from a population-based longitudinal study and assessed for the prevalence of osteoporosis, falls, fractures and medication use. DXA scans were also undertaken. Overall 3.8% (95% confidence interval (CI) 3.2 to 4.5) of respondents and 8.8% (95% CI 7.5 to 10.3) of those aged ≥ 50 years reported that they had been diagnosed with osteoporosis by a doctor. The sensitivity (those self-reporting osteoporosis and having low bone mineral density (BMD) on DXA) was low (22.7%), although the specificity was high (94.4%). Only 16.1% of those aged ≥ 50 years and with DXA-defined osteoporosis were taking bisphosphonates. The sensitivity of self-reporting to identify osteoporosis is low. Anti-osteoporotic medications are an important part of osteoporosis treatment but opportunities to use appropriate medications were missed and inappropriate medications were used.


Effect of adenosine on membrane potential and Ca2+ in juxtaglomerular cells. Comparison with angiotensin II.
Renin is mainly secreted from the juxtaglomerular cells (JGC) in the kidney situated in the afferent arteriole close to the vessel pole. Angiotensin II (ANG II) and adenosine inhibit renin secretion and synergistically constrict the afferent arteriole. ANG II depolarises JGC and increases the cytoplasmic free Ca2+ concentration [Ca2+]i. The responses of JGC to adenosine are less known. Effects of adenosine on membrane potential and [Ca2+]i were studied in afferent arterioles from NaCl-depleted rats and mice. Stimulation of A1 adenosine receptors (A1AR) by adenosine (10 microM) or cyclohexyladenosine (1 microM) increased the spiking frequency of JGC, slightly depolarised the cells and, in < or =50% of the cases, increased [Ca2+]i. These effects were much smaller than those of ANG II (3 nM). Simultaneous application of cyclohexyladenosine and ANG II gave only additive effects on [Ca2+]i; in addition, responses to ANG II in JGC from A1AR knockout mice were similar to those from control mice. The small changes in membrane potential and [Ca2+]i in response to A1AR stimulation as compared to those of ANG II may suggest that these 2 tissue hormones use different signal transduction mechanisms to affect JGC function, including the inhibition of renin release.


[Guardianship law - what doctors and patients should know about the latest amendment].
With the latest amendment of the guardianship law the German legislator means to strengthen the patients' right of self-determination. The most significant new regulations are the introduction of mutual legal representation of married couples in emergency and changes restricting the guardian's legal position. New challenges for doctors and lawyers arise especially from the legal representation of married couples. General practitioners who advise their patients with the preparation of provision documents should particularly explain the importance of recordations in the central providing register (ZVR).


The osteogenic activity of strontium loaded titania nanotube arrays on titanium substrates.
Development of biomedical titanium implants with high osteogenic ability for fast and good osseointegration under normal as well as osteoporotic conditions is hotly pursued. Strontium (Sr) loaded nanotubular structures (NT-Sr) that allow controlled and long-term Sr release are expected to yield favorable osteogenic effects and properties. NT-Sr structures with different tube diameters are fabricated by hydrothermal treatment of titania nanotubes formed at 10 and 40 V (NT10 and NT40). The loaded Sr amounts are regulated by the hydrothermal treatment time of 1 and 3 h (samples NT10-Sr1, NT10-Sr3, NT40-Sr1 and NT40-Sr3) in the Sr(OH)(2) solution. Long lasting and controllable Sr release is observed from the NT-Sr samples with no cytotoxicity. The samples NT10 and NT10-Sr have multiple nanocues, comprising bundles of nanotubes of less than or equal to 30 nm with bundle diameters between 100 and 400 nm separated by about 80 nm. Sr incorporation enhances proliferation of rat mesenchymal stem cells (MSCs) on the NT structure, especially NT10-Sr which promotes the spread of the MSCs into a polygonal osteoblastic shape. Both the NT and NT-Sr samples promote osteogenesis to varying degrees as indicated by gene expression and among the various samples, samples NT10-Sr3 and NT40-Sr significantly up-regulate the expressions of the osteogenesis related genes in the absence of an extra osteogenic agent. Samples NT10 and NT10-Sr generate big nodular alkaline phosphatase (ALP) products and induce extracellular matrix (ECM) mineralization, and the effects on NT10-Sr3 are most obvious due to the multiple scaled nanostructure and proper amount of incorporated Sr. In comparison, less ALP products and failure to induce ECM mineralization are observed from sample NT40-Sr, possibly due to cell function impairment by the uneven protein distribution. NT10-Sr3 which shows excellent osteogenic properties is very attractive and has large clinical potential.


Neurovascular pains: implications of migraine for the oral and maxillofacial surgeon.
Epidemiologic studies have shown that migraine headaches are a common finding in the general population, often associated with a high degree of disability. Additionally, migraine has a reported comorbidity with other medical conditions, most notably with chronic pains, such as temporomandibular disorders. The pathophysiologic mechanisms involved with migraine are suggestive of an increased and prolonged hyperexcitability to stimuli, especially within the trigeminal distribution. Because migraine is mediated by branches of the trigeminal nerve it has the potential to mimic other types of pains, such as toothache or sinusitis. It is therefore recommended that oral and maxillofacial surgeons be familiar with the diagnostic criteria for migraine headaches to identify and appropriately treat such individuals who present to their clinics.


Using balance training to improve the performance of youth basketball players.
The aim of this study was to evaluate the effectiveness of 12 weeks of balance training to improve the balance and vertical jump abilities of young basketball players. Twenty-three players from two teams in the Under Fifteen Basketball Excellence category participated in the study. Participants were divided into two training groups: balance training (BAL, n = 11) and isotonic training (ISO, n = 12). Both groups were tested for balance and vertical jumps at the beginning of the competitive season and at the end of 12 weeks of specific training programme. All of the tests were performed in sustained bipodalic and monopodalic (both right and left) positions. The results showed that players who participated in balance training for 12 weeks, compared to players who trained with isotonic machines, exhibited a significantly increase in balance (bipodalic 28.3 %; right 41.4 %; left 45.8 %; p < 0.01) and muscular power (bipodalic 8.1 %; right 13.5 %; left 12.5 %; p < 0.01) as measured through a vertical jump. In conclusion, balance training using unstable boards was an effective training method for improving balance and the vertical jump, which is a basketball-specific action that frequently occurs in this sport.


Effects of indomethacin and sulindac on hydrochlorothiazide kinetics.
We investigated the influence of two nonsteroidal anti-inflammatory drugs, indomethacin and sulindac, on the diuretic effect and kinetics of hydrochlorothiazide in healthy subjects. In an open, randomized, crossover study, eight healthy subjects were treated with hydrochlorothiazide, 50 mg a day, for 4 weeks. In the second and fourth weeks, indomethacin, 25 mg three times a day, or sulindac, 200 mg twice a day, were added. Blood pressure, body weight, plasma levels of potassium, creatinine, and albumin, the hematocrit, plasma renin activity (PRA), and the 24-hour urinary excretion of sodium and potassium were measured at the end of each week. Plasma concentrations of hydrochlorothiazide and its urinary excretion were also determined 0.5, 1, 2, 3, 4, 8, 10, and 24 hours after HCTZ dosing. When indomethacin was added to hydrochlorothiazide, body weight and plasma potassium levels increased and PRA decreased. Hydrochlorothiazide kinetics were not influenced. In contrast, sulindac decreased the renal clearance of hydrochlorothiazide and increased hydrochlorothiazide plasma levels in two subjects who had somewhat lower endogenous creatinine clearance values than the other subjects. Except for a decrease in PRA, there were no dynamic interactions. Our results suggest that an interaction between indomethacin and hydrochlorothiazide is caused by dynamic mechanisms such as inhibition of renal prostaglandin synthesis, whereas sulindac may alter the renal clearance of hydrochlorothiazide.


What's in a name? The future of drug-resistant tuberculosis classification.
Due to a recent resurgence in tuberculosis research focused on drug development, several new antituberculosis drugs are in the pipeline, and the standard of care for tuberculosis might soon change. If new drugs replace the current first-line treatment, then existing classifications of resistance, including multidrug-resistant and extensively drug-resistant tuberculosis, might become less relevant. When much needed new drugs reach the market, a new classification system for resistance might need to be devised to describe resistance to these novel agents. Many options for such a system exist, each with its own inherent benefits and challenges. The adoption of new terminology for resistance should be guided by outcomes data from clinical trials in progress, and should be accompanied by increased support for drug susceptibility testing in developing countries to be clinically useful. Consideration of these issues now will hopefully help foster an informed approach to the classification of drug-resistant tuberculosis in the era of new drugs.


Prognostic and predictive value of nuclear imaging in endocrine oncology.
In the last few years, the role and use of medical technologies in (neuro)endocrine oncology has greatly evolved allowing not only important diagnostic information but also prognostic stratification in different clinical situations. The terms "prognostic" and "predictive" are commonly used to describe the relationships between biomarkers and patients' clinical outcomes but have quite different meaning. The present work discusses the prognostic and predictive value of nuclear medicine imaging. It critically reviews the clinical significance and potential impact of molecular examinations on follow-up and therapeutic strategies in patients with neuroendocrine neoplasms, thyroid tumors, and adrenal malignancies.


Technical report: analysis of citrated blood with thromboelastography: comparison with fresh blood samples.
Thromboelastography (TEG) evaluates the visco-elastic properties of whole blood to assess clot formation and hemostasis. When blood cannot be analyzed immediately, it is stored in citrated tubes to be analyzed after recalcification. In this study, we evaluated the results of TEG analysis performed on citrated blood and compared these results to values obtained from activated (kaolin and tissue factor) and non activated, fresh blood samples, obtained at various time intervals (one, two, and three hours). Four blood samples were collected from each of ten healthy volunteers. The following TEG analyses were performed on each sample: reaction time (r), k time (k), alpha angle (alpha), and maximum amplitude (MA). Studies were done using fresh, non citrated blood, obtained within five minutes of collection, and using citrated blood, one, two, and three hours after collection. Samples were analyzed, with and without activation, using kaolin and tissue factor. Tissue factor activated and non activated, citrated samples had shorter r and k times (P=0.03, P=0.008, P<0.0001, and P<0.0001, respectively) and higher alpha angle and MA values (P<0.0001, P<0.0001, P=0.79, and P=0.03, respectively) compared to fresh, non citrated samples. These findings were consistent with a hypercoagulable state. Conversely, citrated samples, activated with kaolin, yielded results similar to those obtained from fresh, non citrated samples. The TEG measurements were similar among citrated samples stored from one to three hours. Our results demonstrate that TEG measures, performed on citrated blood samples, yield results that are consistent with a hyperocoagulable state. Using kaolin to activate citrated samples, on the other hand, yields results similar to those obtained from non citrated, fresh blood samples.


Local field potentials of subthalamic nucleus contain electrophysiological footprints of motor subtypes of Parkinson's disease.
Although motor subtypes of Parkinson's disease (PD), such as tremor dominant (TD) and postural instability and gait difficulty (PIGD), have been defined based on symptoms since the mid-1990s, no underlying neural correlates of these clinical subtypes have yet been identified. Very limited data exist regarding the electrophysiological abnormalities within the subthalamic nucleus (STN) that likely accompany the symptom severity or the phenotype of PD. Here, we show that activity in subbands of local field potentials (LFPs) recorded with multiple microelectrodes from subterritories of STN provide distinguishing neurophysiological information about the motor subtypes of PD. We studied 24 patients with PD and found distinct patterns between TD (n = 13) and PIGD (n = 11) groups in high-frequency oscillations (HFOs) and their nonlinear interactions with beta band in the superior and inferior regions of the STN. Particularly, in the superior region of STN, the power of the slow HFO (sHFO) (200-260 Hz) and the coupling of its amplitude with beta-band phase were significantly stronger in the TD group. The inferior region of STN exhibited fast HFOs (fHFOs) (260-450 Hz), which have a significantly higher center frequency in the PIGD group. The cross-frequency coupling between fHFOs and beta band in the inferior region of STN was significantly stronger in the PIGD group. Our results indicate that the spatiospectral dynamics of STN-LFPs can be used as an objective method to distinguish these two motor subtypes of PD. These observations might lead to the development of sensing and stimulation strategies targeting the subterritories of STN for the personalization of deep-brain stimulation (DBS).


Enhanced anaerobic digestion of ammonia-rich swine manure by zero-valent iron: With special focus on the enhancement effect on hydrogenotrophic methanogenesis activity.
Zero-valent iron (ZVI) supplementation for improving anaerobic digestion (AD) of ammonia-rich swine manure (initial ammonia-N ∼5000 mg/L) was tested. The addition of 5 g/L ZVI powder apparently accelerated the acidification process to produce more volatile fatty acids (VFAs) and optimized the fermentation type by contributing to a lower system oxidation-reduction potential (ORP) level of -181.7 to -250.0 mV favorable for ethanol-type and butyric-type fermentation during day 14-30, in comparison with that of -164.3 to -216.3 mV in the control group favorable for propionic-type. Overall, ZVI significantly decreased the proportion of propionic acid from 49.8% to 30.9% while increased the proportion of n-butyric acid from 6.8% to 18.7%. Microbial analysis revealed that fast growing and ammonia-tolerant hydrogenotrophic Methanoculleus species were enriched with ZVI, helping achieve a 54.2% higher CH4 yield relative to control. Results from this study demonstrated the potential of ZVI addition to enhance AD of ammonia-rich animal manure.


Soft, Dynamic Hydrogel Confinement Improves Kidney Organoid Lumen Morphology and Reduces Epithelial-Mesenchymal Transition in Culture.
Pluripotent stem cell-derived kidney organoids offer a promising solution to renal failure, yet current organoid protocols often lead to off-target cells and phenotypic alterations, preventing maturity. Here, various dynamic hydrogel architectures are created, conferring a controlled and biomimetic environment for organoid encapsulation. How hydrogel stiffness and stress relaxation affect renal phenotype and undesired fibrotic markers are investigated. The authors observe that stiff hydrogel encapsulation leads to an absence of certain renal cell types and signs of an epithelial-mesenchymal transition (EMT), whereas encapsulation in soft, stress-relaxing hydrogels leads to all major renal segments, fewer fibrosis or EMT associated proteins, apical proximal tubule polarization, and primary cilia formation, representing a significant improvement over current approaches to culture kidney organoids. The findings show that engineering hydrogel mechanics and dynamics have a decided benefit for organoid culture. These structure-property-function relationships can enable the rational design of materials, bringing us closer to functional engraftments and disease-modeling applications.


Combined use of the cardiofemoral index and middle cerebral artery Doppler velocimetry for the prediction of fetal anemia.
To assess the accuracy of the combined use of the cardiofemoral index (CFI) and the middle cerebral artery peak systolic velocity (MCA-PSV), converted to multiples of the median (MoM), as noninvasive means to detect severe fetal anemia. We measured CFI and MCA-PSV MoM in 37 fetuses just before their first (n=37), second (n=22), and third (n=14) cordocenteses and transfusions. Then, using 2 different criteria for severe fetal anemia detection (Hb deficit ≥7 g/dL and hemoglobin level ≤0.55 of MoM), we assessed their hemoglobin status during cordocentesis and the accuracy of CFI and MCA-PVS was determined. At the first cordocentesis the mean hemoglobin level was 8.5±3.6 g/dL and 15 fetuses (40.5%) had hydrops. In a total of 81 fetal evaluations, 58 (71.6%) of the CFIs and 34 (42.0%) of the MCA-PSV MoM measurements were abnormal. The result of one of these tests was abnormal in 65 evaluations (80.3%) and the results of both tests were abnormal in 27 evaluations (33.3%). All fetuses diagnosed as being severely anemic by at least one of the hemoglobin criteria during cordocentesis had an abnormal result by at least one of the noninvasive tests. Before the second and third transfusions, the combined use of the CFI and MCA-PSV MoM predicted severe fetal anemia with 100% sensitivity. When the CFI and MCA-PSV MoM measurements were normal, the negative likelihood ratio was zero. When associated, CFI and MCA-PSV MoM were accurate predictors of severe fetal anemia.


Map-based cloning, identification and characterization of the w gene controlling white immature fruit color in cucumber (Cucumis sativus L.).
A single-nucleotide insertion resulted in a premature stop codon that is responsible for white immature fruit color in cucumber. Despite our previous progress in the mapping of the gene controlling white color in immature cucumber fruit and the identification of candidate genes, the specific gene that governs chlorophyll metabolism and its regulatory mechanism remains unknown. Here, we generated a mapping population consisting of 9497 F2 plants to delimit the controlling gene to an 8.2-kb physical interval that defines a sole candidate gene, APRR2. Sequencing the full-length DNA and cDNA of APRR2 allowed for identification of an allele, aprr2, encoding a truncated 101-amino acid protein due to a frameshift mutation and a premature stop codon. Gene structure prediction indicated that these 101 residues are located in a domain necessary for the function of the protein. The expression patterns of APRR2 were entirely consistent with the visual changes in green color intensity during fruit development. A microscopic observation of the fruit pericarp revealed fewer chloroplasts and a lower chloroplast chlorophyll storage capacity in Q24 (white) than in Q30 (green). A single-base insertion in the white color gene w, which leads to a premature stop codon, is hypothesized to have disabled the function of this gene in chlorophyll accumulation and chloroplast development. These findings contribute to basic research and the genetic improvement of fruit color.


Delivery of drinking, eating and mobilising (DrEaMing) and its association with length of hospital stay after major noncardiac surgery: observational cohort study.
Enhanced recovery pathways are associated with improved postoperative outcomes. However, as enhanced recovery pathways have become more complex and varied, compliance has reduced. The 'DrEaMing' bundle re-prioritises early postoperative delivery of drinking, eating, and mobilising. We investigated relationships between DrEaMing compliance, postoperative hospital length of stay (LOS), and complications in a prospective multicentre major surgical cohort. We interrogated the UK Perioperative Quality Improvement Programme dataset. Analyses were conducted in four stages. In an exploratory cohort, we identified independent predictors of DrEaMing. We quantified the association between delivery of DrEaMing (and its component variables) and prolonged LOS in a homogenous colorectal subgroup and assessed generalisability in multispecialty patients. Finally, LOS and complications were compared across hospitals, stratified by DrEaMing compliance. The exploratory cohort comprised 22 218 records, the colorectal subgroup 7230, and the multispecialty subgroup 5713. DrEaMing compliance was 59% (13 112 patients), 60% (4341 patients), and 60% (3421), respectively, but varied substantially between hospitals. Delivery of DrEaMing predicted reduced odds of prolonged LOS in colorectal (odds ratio 0.51 [0.43-0.59], P<0.001) and multispecialty cohorts (odds ratio 0.47 [0.41-0.53], P<0.001). At the hospital level, complications were not the primary determinant of LOS after colorectal surgery, but consistent delivery of DrEaMing was associated with significantly shorter LOS. Delivery of bundled and unbundled DrEaMing was associated with substantial reductions in postoperative LOS, independent of the effects of confounder variables. Consistency of process delivery, and not complications, predicted shorter hospital-level length of stay. DrEaMing may be adopted by perioperative health systems as a quality metric to support improved patient outcomes and reduced hospital length of stay.


Overview of Alopecia: A Dermatopathologist's Perspective.
Hair loss affects men and women of all ages and frequently has significant social and psychologic consequences. An awareness and understanding of the various microscopic tests that can be performed is helpful in making an accurate diagnosis. A Dermatopathologist can be an invaluable resource to the clinician.


Non-coding RNA-mediated autophagy in cancer: A protumor or antitumor factor?
Autophagy, usually referred to as macroautophagy, is a cytoprotective behavior that helps cells, especially cancer cells, escape crises. However, the role of autophagy in cancer remains controversial. The induction of autophagy is favorable for tumor growth, as it can degrade damaged cell components accumulated during nutrient deficiency, chemotherapy, or other stresses in a timely manner. Whereas the antitumor effect of autophagy might be closely related to its crosstalk with metabolism, immunomodulation, and other pathways. Recent studies have verified that lncRNAs and circRNAs modulate autophagy in carcinogenesis, cancer cells proliferation, apoptosis, metastasis, and chemoresistance via multiple mechanisms. A comprehensive understanding of the regulatory relationships between ncRNAs and autophagy in cancer might resolve chemoresistance and also offer intervention strategies for cancer therapy. This review systematically displays the regulatory effects of lncRNAs and circRNAs on autophagy in the contexts of cancer initiation, progression, and resistance to chemo- or radiotherapy and provides a novel insight into cancer therapy.


Acute right ventricular infarction.
This article reviews the pathophysiology, hemodynamics, natural history, and management of patients with inferior myocardial infarction complicated by right ventricular infarction. Five key areas are highlighted in which advances may impact catheterization and laboratory management of these acutely ill patients.


Initiative to Improve Postintubation Sedation in a Pediatric Emergency Department.
Previous research has shown that appropriate pediatric postintubation sedation (PIS) after rapid sequence intubation only occurs 28% of the time. Factors such as high provider variability, cognitive overload, and errors of omission can delay time to PIS in a paralyzed patient. To increase the proportion of children receiving timely PIS by 20% within 6 months. A multidisciplinary team identified key drivers and targeted interventions to improve timeliness of PIS. The primary outcome of "sedation in an adequate time frame" was defined as a time to post-Rapid Sequence Intubation sedative administration less than the duration of action of the RSI sedative agent. Secondary outcomes included the proportion of patients receiving any sedation and time to PIS administration. Pediatric postintubation sedation in an adequate time was improved from 27.9% of intubated patients to 55.6% after intervention (p = .001). The number of patients receiving any PIS improved from 74% to 94% (p = .006). The median time from RSI to PIS was reduced from 13 to 9 minutes (p < .001). Process control charts showed a reduction in PIS variability and a centerline reduction from 19 to 10 minutes. Implementation of an intubation checklist and a multidisciplinary approach improved the rate of adequate pediatric PIS.


The psychiatric consequences of trauma.
Trauma can have marked and sustained psychological effects. Those at high risk thereof can be identified, and effective treatments are available. This review provides guidelines for the effective management of the psychiatric sequelae of trauma.


The significance of batch and patch test method in establishing contact allergy to fragrance mix I-EDEN Fragrance Study Group.
A fragrance mix consisting of eight separate fragrance ingredients (fragrance mix I [FM I]) is present in most baseline patch test series. Patch testing with the TRUE Test technique is considered to detect less contact allergy to FM I than testing with the Finn Chamber technique. To investigate the possible significance of batch and patch test method in establishing contact allergy to FM I. Three thousand one hundred and nineteen individuals representing a sample of the general population were patch tested with two batches of FM I with two patch test techniques at six dermatology clinics in five European countries. The TRUE Test technique and the Finn Chamber technique with pet. preparations were used. McNemar's test was used for statistical calculations. The contact allergy prevalences varied between 0.7% and 2.6%. The patch tests with the mixes containing Evernia prunastri (oak moss) with a high content of chloratranol/atranol resulted in substantially more positive reactions than the corresponding tests with the mixes containing oak moss with a low content of chloratranol/atranol. The Finn Chamber technique detected significantly more contact allergic reactions than the TRUE Test technique (P < 0.001). The Finn Chamber technique detects more contact allergy to FM I than the TRUE Test technique.


Observation of discrete diffraction patterns in an optically induced lattice.
We have experimentally observed the discrete diffraction of light in a coherently prepared multi-level atomic medium. This is achieved by launching a probe beam into an optical lattice induced from the interference of two coupling beams. The diffraction pattern can be controlled through the atomic parameters such as two-photon detuning and temperature, as well as orientations of the coupling and probe beams. Clear diffraction patterns occur only near the two-photon resonance.


Arguments against the replacement of type species of the genus Salmonella from Salmonella choleraesuis to 'Salmonella enterica' and the creation of the term 'neotype species', and for conservation of Salmonella choleraesuis.
The proposals of Le Minor and Popoff in 1987 and again of Euzéby in 1999 on the type species of the genus Salmonella are in violation of Rule 20a of the Bacteriological Code (1990 Revision) and should be rejected. The introduction of the term 'neotype species' should be rejected. The specific epithet choleraesuis in the binary combination Salmonella choleraesuis should be conserved. The serovar name Choleraesuis should be changed to Hogcholera.


Linked pools of processed alpha-mannosidase in Dictyostelium discoideum.
We are studying the fate of alpha-mannosidase, a lysosomal enzyme, in Dictyostelium discoideum. alpha-Mannosidase is synthesized as a 150,000-dalton precursor which becomes proteolytically cleaved to mature (56,000-62,000 dalton) forms. When cells are shifted into starvation buffer (5 mM phosphate, pH 6.5), the enzyme is secreted. We compared the kinetics of secretion of newly processed alpha-mannosidase with that of bulk forms. After 2 h in phosphate buffer less than 20% of the newly processed forms but as much as 50% of the bulk enzyme activity was secreted. During the course of the experiments, the total alpha-mannosidase activity remains constant, cells remain viable, and there is no evidence of degradation of enzyme. Furthermore, a 4-h chase period prior to starvation is required before the newly processed forms are secreted to the same extent as the bulk forms. On the basis of these results we propose that the enzyme is present in at least two pools and that it is transferred from a newly processed to an efficiently secreted pool.


Human vascular adhesion proteın-1 (VAP-1): serum levels for hepatocellular carcinoma in non-alcoholic and alcoholic fatty liver disease.
The incidence of hepatocellular cancer in complicated alcoholic and non-alcoholic fatty liver diseases is on the rise in western countries as well in our country. Vascular adhesion protein-1 (VAP-1) levels have been presented as new marker. In our study protocol, we assessed the value of this serum protein, as a newly postulant biomarker for hepatocellular cancer in patients with a history of alcoholic and non-alcoholic fatty liver diseases. Pre-operative serum samples from 55 patients with hepatocellular cancer with a history of alcoholic and non-alcoholic fatty liver diseases and patients with cirrhosis were assessed by a quantitative sandwich ELISA using anti-VAP-1 mAbs. This technique is used to determine the levels of soluble VAP-1 (sVAP-1) in the serum. sVAP-1 levels were evaluated in patients with hepatocellular cancer and liver cirrhosis. There was a significant difference in mean VAP-1 levels between groups. Serum VAP-1 levels were found higher in patients with hepatocellular cancer. These findings indicate that the serum level of sVAP-1 might be a beneficial marker of disease activity in chronic liver diseases.


Simultaneous removal and oxidation of arsenic from water by δ-MnO2 modified activated carbon.
The ubiquitous arsenic in groundwater poses a great risk to human health due to its environmental toxicity and carcinogenicity. In the present work, a new adsorbent, δ-MnO2 modified activated carbon, was prepared, and its performance for the uptake of arsenate and arsenite species from aqueous solutions was investigated by batch experiments. Various techniques, including FESEM-EDX, p-XRD, XPS and BET surface area analysis, were employed to characterize the properties of the adsorbent and the arsenic adsorption mechanisms. The results showed that δ-MnO2 covered on the surface and padded in the pores of the activated carbon. Adsorption kinetic studies revealed that approximately 90.1% and 76.8% of As(III) and As(V), respectively, were removed by the adsorbent in the first 9 hr, and adsorption achieved equilibrium within 48 hr. The maximum adsorption capacities of As(V) and As(III) at pH 4.0 calculated from Langmuir adsorption isotherms were 13.30 and 12.56 mg/g, respectively. The effect of pH on As(V) and As(III) removal was similar, and the removal efficiency significantly reduced with the increase of solution pH. Arsenite oxidation and adsorption kinetics showed that the As(V) concentration in solution due to As(III) oxidation and reductive dissolution of MnO2 increased rapidly during the first 12 min, and then gradually decreased. Based on the XPS analysis, nearly 93.3% of As(III) had been oxidized to As(V) on the adsorbent surface and around 38.9% of Mn(IV) had been reduced to Mn(II) after As(III) adsorption. This approach provides a possible method for the purification of arsenic-contaminated groundwater.


Birth Outcomes in Women Who Have Taken Hydroxycholoroquine During Pregnancy: A Prospective Cohort Study.
Findings from previous small studies have been reassuring regarding the safety of treatment with hydroxychloroquine (HCQ) during pregnancy. In one recent study, it was demonstrated that the frequency of major birth defects was increased in women who had received HCQ at a dose of ≥400 mg/day during pregnancy. This study was undertaken to examine pregnancy outcomes among women following the use of HCQ. The study cohort comprised pregnant women who were prospectively enrolled in the MotherToBaby/Organization of Teratology Information Specialists Autoimmune Diseases in Pregnancy Study and were receiving treatment with HCQ. For the control groups, disease-matched women without HCQ exposure and healthy women were randomly selected from the same source, with subject matching using a 1:1 ratio. Data were collected through interviews, medical records, and dysmorphology examinations. Pregnancy outcome measures included the presence or absence of major and minor birth defects, rates of spontaneous abortion, rates of preterm delivery, and infant growth measures. Between 2004 and 2018, 837 pregnant women met the criteria for study inclusion, including 279 women exposed to HCQ during pregnancy and 279 women in each unexposed control group. Sixty pregnant women (7.2%) were lost to follow-up. Among the women with live births, major birth defects occurred as a pregnancy outcome in 20 (8.6%) of 232 women with HCQ exposure in the first trimester, compared to 19 (7.4%) of 256 disease-matched unexposed controls (odds ratio [OR] 1.18, 95% confidence interval [95% CI] 0.61-2.26) and 13 (5.4%) of 239 healthy controls (adjusted OR 0.76, 95% CI 0.28-2.05). Risks did not differ in women who were receiving an HCQ dose of ≥400 mg/day. No pattern of birth defects was identified. There were no differences in the rates of spontaneous abortion or preterm delivery between groups. Occurrence of infant growth deficiencies did not differ in the HCQ-exposed group compared to the disease-matched unexposed control group, except in the infant's head circumference at birth (adjusted OR 1.85, 95% CI 1.07-3.20). In this study, there was no evidence of an increased risk of structural birth defects or other adverse outcomes among women receiving HCQ during pregnancy, with the exception of infant head circumference at birth. For pregnant women being treated with HCQ, these findings are reassuring.


Positron emission tomography with fluorine-18-fluorodeoxyglucose for the evaluation of therapeutic isolated regional limb perfusion in a patient with soft-tissue sarcoma.
The treatment of a patient with soft-tissue sarcoma was evaluated with FDG-PET. A limb-saving complete remission of a locally advanced liposarcoma of the left thigh was achieved with isolated regional perfusion of the limb with tumor necrosis factor alpha, interferon gamma and melphalan. PET with 18F-FDG before perfusion showed high glucose consumption in the tumor. After perfusion, glucose metabolism in the tumor was absent. Subsequent excision confirmed complete necrosis of the tumor. FDG-PET may be useful in evaluating the results of isolateral regional limb perfusion for soft-tissue sarcomas.


Leishmania infection and neuroinflammation: Specific chemokine profile and absence of parasites in the brain of naturally-infected dogs.
Visceral leishmaniasis is a chronic disease caused by Leishmania infantum. We aimed to detect the parasite in the brain of fifteen naturally-infected dogs using in situ hybridization and immunohistochemistry, and the gene expression of selected chemokines by RT-qPCR. We detected no parasite in the brain, but perivascular deposition of parasite DNA and IgG in the choroid plexus. We noticed up-regulation of CCL-3, CCL-4 and CCL-5, coherent with T lymphocyte accumulation, stating the brain as a pro-inflammatory environment. Indeed, not necessarily the parasite itself, but rather its DNA seems to act as a trigger to promote brain inflammation during visceral leishmaniasis.


Applicability and effectiveness of ultrasound combined with nerve stimulator-guided lumbosacral plexus block in the supine versus lateral position during surgeries for lower limb fracture-a prospective randomized controlled trial.
Patients with lower limb fracture often have acute pain and discomfort from changes in position, and such pain affects early postoperative recovery. This study aimed to compare the applicability and effectiveness of ultrasound combined with nerve stimulator-guided lumbosacral plexus block (LSPB) in the supine versus lateral position during lower limb fracture surgery. We included 126 patients who underwent elective internal fixation for lower limb fracture who were divided into the S group and the L group by the random number table method and underwent LSPB guided by ultrasound combined with a nerve stimulator in the supine and lateral positions, respectively. The primary outcome was the dose of sufentanil used in surgery. The secondary outcomes were the maximum VAS (visual analogue scale) pain score at position placing for LSPB, the time of position placing, the time for nerve block,the number of puncture attempts,the haemodynamic indicators, the VAS score at 1, 12, and 24 h following surgery, postoperative satisfactory degree to analgesia and adverse events related to nerve block. There was no statistically significant difference in dose of sufentanil used between the two groups(P = 0.142). The maximum VAS pain score at position placing(P < 0.01), the time of position placement(P < 0.01), the time for lumbar plexus block and the time of puncture attempts were significantly lower in the S group than in the L group (P < 0.01). However, the time for sacral plexus block was higher in the S group than in the L group (P = 0.029). There was no significant difference in haemodynamic indicators,number of puncture attempts for the sacral plexus, postoperative VAS scores, postoperative satisfactory degree to analgesia or adverse events related to nerve block between the two groups (all P > 0.05). Our study provides a more comfortable and better accepted anaesthetic regimen for patients undergoing lower limb fracture surgery. LSPB in the supine position is simple to apply and has definite anaesthetic effects. Additionally, it has a high level of postoperative analgesia and therefore should be widely applied. The trial was registered prior to patient enrolment at the Chinese Clinical Trail Registry (Date:11/03/2021 Number: ChiCTR2100044117 ).


Fatal Mucormycosis and Aspergillosis in an Atypical Host: What Do We Know about Mixed Invasive Mold Infections?
Mixed invasive mold infections (MIMIs) are considered rare. We present a case of fatal aspergillosis and mucormycosis in an elderly host with history of chronic lymphocytic leukemia (CLL) and potential mold exposures. Notably, he had no classic risk factors for IMI other than high-dose corticosteroids, which may be an important risk factor for (M)IMI, based on the current and previous reports. There is an urgent need for studies on the "net state of immunosuppression," environmental exposure as risk factors for (M)IMIs, and noninvasive fungal diagnostics.


Distinguishing allozymes and isozymes of phosphoglucoisomerases by electrophoretic comparisons of pollen and somatic tissues.
The different electrophoretic patterns of dimeric phosphoglucoisomerases extracted from haploid pollen and diploid somatic tissues of plants may be used to distinguish allozymes and isozymes. The analysis depends on the presence of two alleles at each locus in somatic tissues but only one or the other allele in pollen grains. Consequently, in heterozygotes, heterodimeric allozymes can be identified because they are formed in stems and leaves but not in pollen. The procedure is described in enzymes extracted from the diploid annual plant Clarkia dudleyana, which possesses three gene loci for PGI subunits. Comparison of the electrophoretic patterns of stem and pollen extracts makes it possible in many cases to identify allelic state without breeding tests. The technique also is likely to be useful in the interpretation of zymograms of other multimeric enzymes coded by more than one gene locus.


Exploiting natural antiviral immunity for the control of pandemics: Lessons from Covid-19.
The outbreak of coronavirus disease 2019 (COVID-19), triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the disruptive global consequences in terms of mortality and social and economic crises, have taught lessons that may help define strategies to better face future pandemics. Innate and intrinsic immunity form the front-line natural antiviral defense. They involve both tissue-resident and circulating cells, which can produce anti-viral molecules shortly after viral infection. Prototypes of these factors are type I interferons (IFN), antiviral cytokines with a long record of clinical use. During the last two years, there has been an impressive progress in understanding the mechanisms of both SARS-CoV-2 infection and the cellular and soluble antiviral responses occurring early after viral exposure. However, this information was not sufficiently translated into therapeutic approaches. Insufficient type I IFN activity probably accounts for disease progression in many patients. This results from both the multiple interfering mechanisms developed by SARS-CoV-2 to decrease type I IFN response and various pre-existing human deficits of type I IFN activity, inherited or auto-immune. Emerging data suggest that IFN-I-mediated boosting of patients' immunity, achieved directly through the exogenous administration of IFN-β early post viral infection, or indirectly following inoculation of heterologous vaccines (e.g., Bacillus Calmette Guerin), might play a role against SARS-CoV-2. We review how recent insights on the viral and human determinants of critical COVID-19 pneumonia can foster clinical studies of IFN therapy. We also discuss how early therapeutic use of IFN-β and prophylactic campaigns with live attenuated vaccines might prevent a first wave of new pandemic viruses.


Mutations of complement lectin pathway genes MBL2 and MASP2 associated with placental malaria.
Innate immunity plays a crucial role in the host defense against malaria including Plasmodium falciparum malaria in pregnancy, but the roles of the various underlying genes and mechanisms predisposing to the disease are poorly understood. 98 single-nucletoide polymorphisms were genotyped in a set of 17 functionally related genes of the complement system in 145 primiparous Ghanaian women with placental malaria, defined by placental parasitaemia or malaria pigment, and as a control, in 124 non-affected primiparae. Placental malaria was significantly associated with SNPs in the lectin pathway genes MBL2, MASP2, FCN2 and in properdin. In particular, the main African mannose-binding lectin deficiency variant (MBL2*G57E, rs1800451) increased the odds of placental malaria (OR 1.6; permuted p-value 0.014). In contrast, a common MASP2 mutation (R439H, rs12085877), which reduces the activity of MBL-MASP2 complexes occurred in 33% of non-affected women and in 22% primiparae with placental malaria (OR 0.55, permuted p-value 0.020). Excessive complement activation is of importance in the pathogenesis of placental malaria by mediating inflammation, coagulation, and endothelial dysfunction. Mutated MBL and MASP2 proteins could have direct intrinsic effects on the susceptibility to placental malaria, in addition to their roles in regulation of downstream complement activation.


Purification and characterisation of two extremely halotolerant xylanases from a novel halophilic bacterium.
The present work reports for the first time the purification and characterisation of two extremely halotolerant endo-xylanases from a novel halophilic bacterium, strain CL8. Purification of the two xylanases, Xyl 1 and 2, was achieved by anion exchange and hydrophobic interaction chromatography. The enzymes had relative molecular masses of 43 kDa and 62 kDa and pI of 5.0 and 3.4 respectively. Stimulation of activity by Ca(2+), Mn(2+), Mg(2+), Ba(2+), Li(2+), NaN(3) and isopropanol was observed. The K(m) and V(max) values determined for Xyl 1 with 4- O-methyl- d-glucuronoxylan are 5 mg/ml and 125,000 nkat/mg respectively. The corresponding values for Xyl 2 were 1 mg/ml and 143,000 nkat/mg protein. Xylobiose and xylotriose were the major end products for both endoxylanases. The xylanases were stable at pH 4-11 showing pH optima around pH 6. Xyl 1 shows maximal activity at 60 degrees C, Xyl 2 at 65 degrees C (at 4 M NaCl). The xylanases showed high temperature stability with half-lives at 60 degrees C of 97 min and 192 min respectively. Both xylanases showed optimal activity at 1 M NaCl, but substantial activity remained for both enzymes at 5 M NaCl.


Biomass-derived carbon dots with light conversion and nutrient provisioning capabilities facilitate plant photosynthesis.
Carbon dots (CDs)-enabled agriculture has been developing rapidly, but small-scale synthesis and high costs hinder the agricultural application of CDs. Herein, biomass-derived carbon dots (B-CDs) were prepared on a gram-level with low cost, and these B-CDs significantly improved crop photosynthesis. The B-CDs, exhibiting small size and blue fluorescence, were absorbed by crops and enhanced photosynthesis via light-harvesting. Foliar application of B-CDs (10 mg·kg-1) could promote chlorophyll synthesis (30-100 %), Ferredoxin (Fd, 40-80 %), Rubisco enzyme (20-110 %) and upregulated gene expression (20-70 %), resulting in higher net photosynthetic rates (130-300 %), dry biomass (160-300 %) and fresh biomass (80-150 %). Further, the B-CDs could increase crop photosynthesis under nutrient deficient conditions, which was attributed to the release of nutrients from B-CDs. Therefore, the B-CDs enhanced the photosynthesis via enhancing light conversion and nutrient supply. This study provides a promising material capable of enhancing photosynthesis for sustainable agriculture production.


Angiogenesis inhibitor TNP-470 (AGM-1470) suppresses vascular smooth muscle cell proliferation after balloon injury in rats.
Although TNP-470, a synthetic analog of fumagillin, may inhibit vascular intimal hyperplasia, the effects of TNP-470 on smooth muscle cell (SMC) proliferation have not been demonstrated in vivo. The aim of this study was to confirm the effect of TNP-470 on vascular SMC proliferation using a rat carotid artery balloon injury model. Rats were treated with vehicle or with TNP-470 at low dosage (10 mg/kg), medium dosage (20 mg/kg), or high dosage (40 mg/kg). The animals received subcutaneous injections of materials three times a week from the day following balloon injury. All rats were sacrificed at 2 weeks after injury. The ratio of intimal-to-medial cross-sectional areas (I/M ratio) and the PCNA labeling index was calculated for each group. The DNA synthesis of cultured SMCs was also evaluated using [3H]thymidine incorporation assays. Smooth muscle cells were stimulated with basic fibroblast growth factor and TNP-470 (0.01-100 ng/ml) were added. The inhibition of intimal hyperplasia increased in a dose-dependent manner. TNP-470 also decreased PCNA expression in the neointima and inhibited DNA synthesis of cultured SMCs. TNP-470 may be useful in the prevention of vascular intimal hyperplasia.


Hepatic granulomas in Whipple's disease.
Hepatic epithelioid cell granulomas that were negative for periodic acid-Schiff stain after diastase digestion were found in a 32-yr-old man who presented with painless hepatomegaly and slight fever. The patient never complained of intestinal symptoms, which in part explains why the diagnosis of Whipple's disease was made only 3 mo later, at a time when severe neurologic manifestations had appeared. The definitive diagnosis was made on the basis of the characteristic histologic findings in biopsy material obtained from jejunum and abdominal lymph nodes at laparotomy. The patient's condition, especially neurologic manifestations, rapidly improved after antibiotic therapy. It is noteworthy that Whipple's disease is generally not included among the causes of hepatic epithelioid cell granulomas. It is suggested that its possibility should be considered in patients with hepatic granulomas without obvious etiology, even in the absence of intestinal symptoms.


The contact angle induced by DPL at pulmonary epithelial surfaces.
A contact angle has been measured at the surface of dog tracheal epithelium by means of two surface balances simultaneously monitoring the apparent surface tension of the same film in a Langmuir trough - one method dependent upon contact angle and the other independent of contact angle. This was confirmed by direct observation. The contact angle was absent for Ringer's solution alone but was induced by DPL deposited on the fluid surface in physiological concentrations. The contact angle varied from 9 degrees to 67 degrees for compression of the DPL film from 100% to 27.5% of its original area and displayed hysteresis with respect to area. These findings show that DPL has unusual surface properties in reducing surface tension yet decreasing wettability, i.e. acting as an anti-wetting agent. The physiological advantages of this unusual combination of properties are discussed in relation to maintaining pulmonary homeostasis and the forward propulsion of mucus which could be facilitated by the differential wettability of cilia induced by DPL. One possible disadvantage of DPL is indicated where fluid plugs might seal an airway - such as in the newborn.


Micropore filling fabrication of high resolution patterned PQDs with a pixel size less than 5 μm.
PQDs are promising color converters for micro-LED applications. Here we report the micropore filling fabrication of high resolution patterned PQDs with a pixel size of 2 μm using a template with SU8 micropores.


Preventive strategies, exercises and rehabilitation of hand neuropathy in cyclists: A systematic review.
Recreation, transportation and sport are the most common uses of bicycles. Unfortunately, repetitive bicycle use can also cause injuries, such as osteoarticular direct and undirect traumatisms and sometimes compression nerve entrapment caused by an extrinsic compressive force. The aim of the study is to define diagnostic process, preventive strategies, and treatment of ulnar and median neuropathies in cyclists. Systematic review. A search was conducted on PubMed, EMBASE, the Cochrane Library, and Web of Science. Two reviewers independently reviewed articles and came to a consensus about which ones to include. The authors excluded all duplicates, articles involving individuals with other sport-related injuries than cycling, and articles unrelated to peripheral neuropathies. Articles were included if hand palsy was due to peripheral compression of ulnar or median nerve in cyclists. The search identified 15,371 articles with the keywords "Peripheral Nervous System Diseases" OR "neuropathy" OR "ulnar palsy" OR "median palsy" AND "bicycling" OR "bike" OR "bicycle" OR "cyclist". The reviewers analyzed 48 full texts. There were 20 publications that met the criteria and were included in the systematic review. These articles were used to describe the main methods used for diagnosis, prevention and treatment of hand neuropathy of cyclists. Despite the range of treatment available for peripheral neuropathies, a unique and common protocol is lacking on this specific topic. For this reason, we delineate a definitive recovery protocol to show the best therapeutic methodologies present in the current literature. Preventive strategies, period of rest since the beginning of the symptomatology, rehabilitation training with muscle strengthening, orthoses at night are the first strategies, but if the symptoms persist, pharmacologic treatment and eventual surgical decompression are sometimes the unique solution.


Hereditary nasal parakeratosis in Labrador retrievers: 11 new cases and a retrospective study on the presence of accumulations of serum ('serum lakes') in the epidermis of parakeratotic dermatoses and inflamed nasal plana of dogs.
We report 11 new cases of hereditary nasal parakeratosis in Labrador retrievers. The disease was first observed when the dogs were 6 months to 2 years of age, and affected dogs of either sex and all coat colours. Hyperkeratosis and depigmentation were confined to the nasal planum, and affected dogs were otherwise healthy. The principal histological findings in biopsy specimens were marked diffuse parakeratotic hyperkeratosis, multiple intracorneal serum lakes and superficial interstitial-to-interface lymphoplasmacytic dermatitis. Topical applications of propylene glycol in water or white petrolatum were often effective for treatment of the dermatosis. However, continued applications were required to maintain a beneficial response. A retrospective histological study of parakeratotic inflammatory diseases of canine haired skin and inflammatory diseases of the canine nasal planum was performed. The degree of parakeratotic hyperkeratosis and the number and size of intracorneal serum lakes were evaluated. The degree of parakeratotic hyperkeratosis was greater in hereditary nasal parakeratosis specimens than that seen in discoid lupus erythematosus and Malassezia dermatitis. There were more serum lakes in hereditary nasal parakeratosis specimens than in specimens from dogs with discoid lupus erythematosus, Malassezia dermatitis, primary seborrheic dermatitis or zinc-responsive dermatosis. Significant differences in sizes of serum lakes (if present) were not seen.


[Genetic Differentiation of Balkhash Perch Perca schrenki Kessler, 1874 from Lake Balkhash and Alakol Lake System of Kazakhstan].
The genetic differentiation of two populations of Balkhash perch Perca schrenki Kessler, 1874 was examined. The study included (1) the population of Lake Balkhash and the Ili River delta, where this species is protected and it is prohibited to catch them and (2) the population of Alakol Lake system, where it is the main commercial species and forms two morphotypes--pelagic and coastal. Analysis of the mitochondrial DNA COI gene and. six microsatellite loci revealed genetic differentiation at the population level, while no statistically significant differences were found at the morphotype level. The results of this study make it possible with high probability to determine the belonging of caught fish to either the commercial (Alakol Lake system) or protected (Lake Balkhash) population.


Risk Prediction Model Versus United States Preventive Services Task Force Lung Cancer Screening Eligibility Criteria: Reducing Race Disparities.
Disparities exist in lung cancer outcomes between African American and white people. The current United States Preventive Services Task Force (USPSTF) lung cancer screening eligibility criteria, which is based solely on age and smoking history, may exacerbate racial disparities. We evaluated whether the PLCOm2012 risk prediction model more effectively selects African American ever-smokers for screening. Lung cancer cases diagnosed between 2010 and 2019 at an urban medical center serving a racially and ethnically diverse population were retrospectively reviewed for lung cancer screening eligibility based on the USPSTF criteria versus the PLCOm2012 model. This cohort of 883 ever-smokers comprised the following racial and ethnic makeup: 258 white (29.2%), 497 African American (56.3%), 69 Hispanic (7.8%), 24 Asian (2.7%), and 35 other (4.0%). Compared with the USPSTF criteria, the PLCOm2012 model increased the sensitivity for the African American cohort at lung cancer risk thresholds of 1.51%, 1.70%, and 2.00% per 6 years (p < 0.0001). For example, at the 1.70% risk threshold, the PLCOm2012 model identified 71.3% African American cases, whereas the USPSTF criteria only identified 50.3% (p < 0.0001). In contrast, in case of whites there was no difference (66.0% versus 62.4%, respectively [p = 0.203]). Of the African American ever-smokers who were PLCO1.7%-positive and USPSTF-negative, the criteria missed from the USPSTF were those with pack-years less than 30 (67.7%), quit time of greater than 15 years (22.5%), and age less than 55 years (13.0%). The PLCOm2012 model was found to be preferable over the USPSTF criteria at identifying African American ever-smokers for lung cancer screening. The broader use of this model in racially diverse populations may help overcome disparities in lung cancer screening and outcomes.


Hydrothermal synthesis of needle-shaped manganese oxide nanoparticle for superior adsorption of thallium(I): characterization, performance, and mechanism study.
Thallium as a highly toxic metal element has been listed as one of priority drinking water contaminants. In this study, manganese oxide nanoparticles were synthesized through a simple hydrothermal method and applied for the removal of thallium(I). The adsorbent was composed of numerous needle-like nanorods and had an average volume diameter of 230 nm after heat-drying procedure. The crystal form of adsorbent was determined as α-MnO2. The adsorbent exhibited a much faster adsorption rate than most of previously reported adsorbent, achieving over 66.4% of equilibrium adsorption capacity in the first 10 min. The adsorption process was found to be highly affected by solution pH and higher than 100 mg/g of adsorption capacity could be obtained in a wide pH range of 6.0-10.0. The isotherm study indicated that the adsorption of Tl(I) on the adsorbent was favorable and governed by a chemisorption process, with the maximum adsorption capacity of 505.5 mg/g at pH 7.0. The adsorption process was confirmed to be thermodynamically spontaneous and endothermic. The presence of Na+, K+, Mg2+, Ca2+, and Cu2+ cations had certain negative effects on the uptake of Tl(I). Based on the batch experiments and XPS analysis, the deprotonated hydroxyl groups that bonded to manganese atoms worked as the binding sites for the effective removal of Tl(I) ions and no redox reaction occurred during the adsorption process.


The significance of serum S100 calcium-binding protein A4 in silicosis.
Silicosis is a chronic occupational pulmonary disease characterized by persistent inflammation and irreversible fibrosis. Considerable evidences now indicate that S100 calcium-binding protein A4 (S100A4) has been associated with fibrotic diseases. However, the role of S100A4 in silicosis is still unclear. In this study, serum levels of S100A4, transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in patients with silicosis (n = 42) and control group (CG, n = 12) were measured by ELISA. S100A4 expression in lung tissues and primary alveolar macrophages (AMs) of mice with and without silicosis was detected by immunohistochemistry (IHC)/real-time PCR. The correlations between S100A4 and cytokines or lung function were assessed by Spearman's rank correlation analyses. Compared with CG, the levels of S100A4 were significantly increased in silicosis patients (70.84 (46.22, 102.46) ng/ml vs (49.84 (42.86, 60.02) ng/ml). The secretions of TGF-β1, CTGF, IL-6 and TNF-α in silicosis group were significantly higher than that in control group (p < 0.05). Serum S100A4 levels were positively correlated with TGF-β1 and IL-6, while were negatively correlated with lung function parameters including percentage of predicted forced vital capacity (FVC%pre), maximum vital capacity (Vcmax), deep inspiratory capacity (IC) and peak expiratory flow at 75% of vital capacity (PEF75). In receiver operating characteristic (ROC) analyses, S100A4 > 61.7 ng/ml had 63.4% sensitivity and 83.3% specificity for silicosis, and the area under the curve (AUC) was 0.707. Furthermore, immunostaining of lung tissues showed the accumulation of S100A4-positive cells in the areas of nodules of silicotic mice. The mRNA expression of S100A4 in the lung tissues and AMs of silicotic mice were significantly higher than controls. These data suggested that increased S100A4 might contribute to the pathogenesis of silicosis.


A sensitive spectrofluorometric method for detection of berberine hydrochloride using Ag nanoclusters directed by natural fish sperm DNA.
A novel DNA-directed AgNCs (DNA-AgNCs) was synthesized with economical raw material (natural fish sperm DNA) through a simple and rapid approach, and it first showed high and stable fluorescence emission as a AgNCs stabilized by natural DNA at about 635nm. Moreover, its emission intensity could be enhanced tremendously in acetic acid (HAc) medium. Whereas, when berberine hydrochloride (BRH) entered the solution system, it would interact and combine efficiently with DNA on the surface of AgNCs, which could lead to subtle change of charge distribution on its surface, and make it more lyophobic, inducing aggregation of DNA-AgNCs. As a result, fluorescence of the system was quenched visually; the process represented a color variance from yellow to hot pink under HAc medium, then back to yellowish-brown when BRH worked. Based on above phenomenon, a selective and accurate spectrofluorometric method for BRH detection was established. It can be applied to detect trace amounts of BRH in aqueous solution in the linear range from 1.0nM to 2000.0nM; and the detection limit (3σ/k) was 0.3nM, which is pretty lower compared to most reported spectral methods. Simultaneously, a semi-quantitative determination by visual evaluation from 5.0nM to 2000.0nM was also achieved. This method provided excellent selectivity for the detection of BRH in the presence of ten kinds of common natural amino acids and nine kinds of common mental ions. Furthermore, the BRH content in compound berberine tablets from drugstore was successfully investigated by this method and the results showed high accuracy.


Short-step syntheses of naturally occurring polyoxygenated aromatics based on site-selective transformation.
Wogonin and astringin were synthesized from inexpensive chrysin and piceid in short steps. The key feature of these syntheses is site-selective transformation. The target molecules were obtained in 27 and 62% yields from the starting materials, respectively.


Donor platelets stored for at least 3 days can elicit activation marker expression by the recipient's blood mononuclear cells: an in vitro study.
Recent studies have demonstrated that infused platelets (PLTs) can promote inflammation. The objective of this study was to evaluate the impact of storage of transfusion-grade PLTs on the peripheral blood mononuclear cells (PBMNCs) of the recipient. An in vitro cell model system was established to measure the degree of activation of donor PLTs during 5 days of their storage and then to measure immune cell activation by detecting marker expression in coculture experiments. The level of soluble CD62p increased significantly by Day 3, and membrane expression of CD62p increased significantly from Day 2, indicating some degree of PLT activation over time during storage (p < 0.05). Donor PLTs and PBMNC subsets (monocytes, B cells, and T cells) from recipients were cocultured for 48 hours. The number of PLT-PBMNC subset doublets detected by flow cytometry was correlated with the PLT storage time after Day 3 (p < 0.05), indicating consistent binding of PLTs to PBMNCs. The results of these experiments showed that there was a consistent and significant increase in expression of conventional activation markers of T cells, B cells, and monocytes compared with appropriate controls (p < 0.05 to <0.01). The results of this study indicate that, from Day 3 onward, activation markers are consistently expressed on PLTs. From these results, we conclude that activated PLTs may affect PBMNC interactions in recipients.