Challenges of Accessing Care in Art Clinic during COVID-19 Lockdown in Lagos.
As the SARS-CoV-2 pandemic continues to ravage the world, its impact on the health systems and survival of people with chronic diseases especially People living with HIV [PLWH] could be undermined. It becomes relevant to assess the challenges PLWH face during this period to institute measures towards combating the negative effects of the pandemic. This study aims to investigate the challenges faced by PLWH in accessing care during the lockdown period in Lagos, Nigeria. The study was a cross-sectional one involving PLWH aged 18 years and above who presented for care. An interviewer-administered questionnaire was used to obtain information on demographic characteristics, their knowledge about COVID-19 disease, and challenges experienced in accessing care during the COVID-19-induced lockdown. Ethical approval was obtained from the Institution Research Ethics Board (IRB) of NIMR. Data generated from the survey was exported to Excel and analyzed using SPSS version 23.0. The mean age of PLWH who participated in the study was 42.2 (±12.2) years. The majority were female (74.3%), married (66.3%), employed (58.9%), and on less than $100 monthly income (80.5%). The commonest challenges experienced were psychological (78.5%), financial (68%) and food (40.7%). There were significant association among the income status, lack of food (OR: 2.5, CI: 1.4-4.5, P = 0.002), financial challenges (OR: 1.7, CI: 1.0-3.0, P = 0.048) and psychological challenges (OR; 1.8, CI: 1.0-3.5, P = 0.05). Ninety-five percent of participants believed SARS-COV-2 infection is a viral infection. PLWH faces a myriad of challenges that would have a significant impact on their overall well-being and the gains of HIV care.


Recent studies on lonidamine, the lead compound of the antispermatogenic indazol-carboxylic acids.
Lonidamine (LND) or [1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid] is an anticancer and an antispermatogenic drug whose mechanism of action is still incompletely understood. LND is effective against a number of tumors, including head, neck and breast cancers, probably because of the inhibition of mitochondrial electron transport and the enzyme hexokinase and to the induction of apoptosis. Instead, the antispermatogenic activity of LND appeared to be related not only to its energolytic activity but also to other effects activities such as the inhibition of specific chloride channels in the epididymis and the disruption of the inter-Sertoli-germ cell junctions, leading to premature release of germ cells. In addition, we recently reported that, in the rat, LND at the dose of 100 mg/Kg b.w. p.o., a fully active but well tolerated dose, caused specific changes of the testicular and epididymal macroglobulins (alpha(2)-macroglobulin, alpha(1) inhibitor-3 and alpha(1)-macroglobulin). Further studies are needed to elucidate the mechanism of action of LND, the lead compound of an interesting class of antispermatogenic drugs based on the core structure of 1-(2,4-dichlorobenzyl)-indazole-3-carboxylic acid.


The relationship between hepatic low-density lipoprotein receptor activity and serum cholesterol level in the human fetus.
We found that the binding of 125I-low-density lipoprotein to fetal liver low-density lipoprotein receptor rose progressively with the increase in fetal age. During this period, total cholesterol and low-density lipoprotein-cholesterol levels in fetal serum declined significantly. The correlation coefficients between fetal age and concentration of serum total cholesterol and low-density lipoprotein cholesterol were -0.80 (p less than 0.001) and -0.77 (p less than 0.001), respectively. A significant inverse correlation also existed between the liver low-density lipoprotein receptor activity and the serum total cholesterol (r = -0.96, p less than 0.001) and low-density lipoprotein cholesterol (r = -0.95, p less than 0.001) but not high-density lipoprotein cholesterol. It is suggested that the low-density lipoprotein receptors in human fetal liver may play a key role in the regulation of the serum cholesterol levels during gestation.


Oxoammonium Salt-Mediated Regioselective Vicinal Dioxidation of Alkenes: Relying on Transient and Persistent Nitroxides.
A novel, easy-to-handle, and regioselective vicinal dioxidation of alkenes under transition metal and organic peroxide free conditions has been developed. This approach uses N-hydroxyphthalimide and its analogues as the transient nitroxyl-radical precursors and 2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (TEMPO+BF4-) as the oxidant as well as the source of persistent nitroxide. By employing this method, multifarious structurally important dioxidation products were efficiently synthesized from simple alkenes and complex bioactive molecule derivatives.


Arachnoid cysts: does surgery improve epileptic seizures and headaches?
During the period from 1985 to 1992 we treated 43 patients with intracranial arachnoid cysts (ACs). In this retrospective study we assessed the outcome of these patients with regard to non-specific symptoms such as headaches and epileptic seizures. Twelve patients had headaches of obscure origin and a mostly temporal located AC. Six of these 12 underwent surgery. After the operation 4 patients (4/6) had no further headaches, two remained unchanged. The other 6 conservatively treated patients (6/12) had further headaches. Ten of the 43 patients had epileptic seizures. One patient dropped out of the survey. Six of the 9 remaining patients had a temporal AC. Four of these 6 underwent surgery; postoperatively the seizure disease of 3 patients (3/6) declined. One patient was unchanged. Two patients with epileptic seizures and a temporal AC did not undergo surgery and both improved. Three patients with seizures had a convex located AC. Two of these 3 underwent surgery. The first patient improved postoperatively, the second patient remained unchanged. There was a reduction in the seizures of the medically treated patient. It remains ambiguous, whether there is a relationship between epileptic seizures and intracranial ACs without obvious intracranial pressure signs. A review of the literature, however, showed mostly positive results concerning the surgical treatment of ACs under conditions of simultaneous epileptic seizures. However, the results largely depend upon the definition of the decline of the seizures with regard to the postoperative follow-up, therefore we must remain skeptical. Therapy guidelines in the future not only depend on the clarification of the pathophysiology of the ACs, but also on a resonable outcome examination.


Pharmacological and philosophical considerations for the around-the-clock use of scheduled melatonin to promote sedation and reduce aggression in individuals with serious mental illness: a case report.
Melatonin, the endogenous hormone that helps maintain circadian rhythm, has been used exogenously for both primary and secondary sleep disorders. While the effects of melatonin given prior to planned sleep and to restore normal circadian sleep phases have been well studied, there is little information on the use of melatonin as a pharmacotherapeutic intervention for around-the-clock sedation to prevent agitation and aggressive patient behaviors. This is the first case report to our knowledge of melatonin used throughout the day, as a scheduled dose for prolonged treatment duration, to reduce aggression in a patient with severe mental illness.


Lip and Oral Cavity Cancer Burden and Related Risk Factors in China: Estimates and Forecasts from 1990 to 2049.
Lip and oral cavity cancer is a common malignancy faced by many developing countries, and the disease burden is high in China. This study explored this cancer burden and its risk factors using data from China in the GBD 2019, along with predicting the incidence trends in 2020-2049. Data on age-standardized rates (ASR), incidence, death and disability-adjusted life years (DALY), by sex, age and risk factors were collected from the Institute for Health Metrics and Evaluation (IHME). Joinpoint regression and Age-Period-Cohort (APC) models were selected to analyze the epidemic trend of this cancer in China, and descriptive analysis was used for the time trend and age distribution of risk factors. The Bayesian APC model was selected to foresee the incidence trend in 2020-2049. This cancer burden was found to be in an upward trend in China in 1990-2019. The upward trend was more pronounced among men than among women. These cancer deaths and DALYs are overwhelmingly attributable to smoking and drinking. On APC analysis, the younger generation in China demonstrated a lower cancer risk. In 2049, the incidence of this cancer is projected to be 3.99/100,000, 6.07/100,000, 7.37/100,000, 10.49/100,000, 14.82/100,000, 19.19/100,000, 20.71/100,000, 23.64/100,000, 16.42/100,000 and 9.91/100,000 among those aged 50-54, 55-59, 60-64, 65-69, 70-74, 75-79, 80-84, 85-89, 85-89 and over 95 years, respectively. Disease control policies and early screening should focus on men and the elderly and target different risk factors.


Correlation between molecular charge densities and sensitivity of nitrogen-rich heterocyclic nitroazole derivative explosives.
Nitroazole derivatives are nitrogen-rich heterocyclic ring molecules with potential application as energetic materials. Thirty-three of them-nitroimidazoles, nitrotriazoles, and nitropyrazoles-were investigated. Computed density functional theory molecular charge densities were partitioned employing the accurate distributed multipole analysis (DMA) method. Based on the magnitude of the DMA atom-centered electric multipoles (monopole, dipole, and quadrupole values), mathematical models were developed to compute the impact sensitivity of the explosives composed of these molecules. Charge localization and delocalization of the ring nitrogen atoms as well as charges of the atoms of the nitro group affect the sensitivity of explosives composed of nitroazole derivatives. The sensitivity is strongly dependent on the ring position of the nitrogen atoms and the bonding site of the substituent groups. The N/C ratio and the repulsion of the non-bonding electron pairs of the vicinal nitrogen atoms of the ring also play an important role in the stability of nitroazoles. The influence of the withdrawing group (NO2) and the electron injector groups (NH2 and CH3) including their bonding position on the ring could be quantified.


Characterization of four Rhodococcus alcohol dehydrogenase genes responsible for the oxidation of aromatic alcohols.
Four genes were isolated and characterized for alcohol dehydrogenases (ADHs) catalyzing the oxidation of aromatic alcohols such as benzyl alcohol to their corresponding aldehydes, one from o-xylene-degrading Rhodococcus opacus TKN14 and the other three from n-alkane-degrading Rhodococcus erythropolis PR4. Various aromatic alcohols were bioconverted to their corresponding carboxylic acids using Escherichia coli cells expressing each of the four ADH genes together with an aromatic aldehyde dehydrogenase gene (phnN) from Sphingomonas sp. strain 14DN61. The ADH gene (designated adhA) from strain TKN14 had the ability to biotransform a wide variety of aromatic alcohols, i.e., 2-hydroxymethyl-6-methylnaphthalene, 2-hydroxymethylnaphthalene, xylene-alpha,alpha'-diol, 3-chlorobenzyl alcohol, and vanillyl alcohol, in addition to benzyl alcohol with or without a hydroxyl, methyl, or methoxy substitution. In contrast, the three ADH genes of strain PR4 (designated adhA, adhB, and adhC) exhibited lower ability to degrade these alcohols: these genes stimulated the conversion of the alcohol substrates by only threefold or less of the control value. One exception was the conversion of 3-methoxybenzyl alcohol, which was stimulated sevenfold by adhB. A phylogenetic analysis of the amino acid sequences of these four enzymes indicated that they differed from other Zn-dependent ADHs.


The impact of graph construction scheme and community detection algorithm on the repeatability of community and hub identification in structural brain networks.
A critical question in network neuroscience is how nodes cluster together to form communities, to form the mesoscale organisation of the brain. Various algorithms have been proposed for identifying such communities, each identifying different communities within the same network. Here, (using test-retest data from the Human Connectome Project), the repeatability of thirty-three community detection algorithms, each paired with seven different graph construction schemes were assessed. Repeatability of community partition depended heavily on both the community detection algorithm and graph construction scheme. Hard community detection algorithms (in which each node is assigned to only one community) outperformed soft ones (in which each node can belong to more than one community). The highest repeatability was observed for the fast multi-scale community detection algorithm paired with a graph construction scheme that combines nine white matter metrics. This pair also gave the highest similarity between representative group community affiliation and individual community affiliation. Connector hubs had higher repeatability than provincial hubs. Our results provide a workflow for repeatable identification of structural brain networks communities, based on the optimal pairing of community detection algorithm and graph construction scheme.


Semantic processing of Arabic, Kanji, and Kana numbers: evidence from interference in physical and numerical size judgments.
Two experiments were conducted with the following objectives (1) to replicate the finding of similar semantic representation of Arabic and written-word (Kanji and Kana) numbers with a direct numerical task, (2) to investigate the automatic semantic processing of Arabic and written-word numbers, and (3) to verify whether the assumption of a common semantic representation is valid in an indirect numerical task. Subjects were asked to judge which of two numbers (e.g, 6-8) was larger either in its numerical size (Experiment 1) or in its physical size (Experiment 2) using the three notations. Effects of two factors were analyzed: the congruity between numerical and physical size and the numerical distance. The effects of these factors were very similar across the three notations in Experiment 1, but were drastically different in Experiment 2. The results of Experiment 2 demonstrated the nonsemantic processing of Kana numbers, and suggest that there may be separate semantic representations for Arabic and Kanji numbers.


On the way to reduce marine microplastics pollution. Research landscape of psychosocial drivers.
Current human lifestyle generates enormous amounts of plastics and microplastics that end in the ocean and threaten marine life. Exposure to microplastics seems to threaten human health too. Although the degree of damage is not clear yet, precautionary approach urgently requires a change of societal habits. The objective of this study was to discover emerging issues of priority for psychosocial investigation. For this we have compared the landscape research of Reviews with that of Perspectives articles of the last decade, to identify mismatches that unravel still understudied subjects. Results revealed that circular economy is a focus in Perspectives but is not main topic of current psychosocial research. Regarding the actors involved in the change towards circular economy, although companies are priority in Perspectives current research is focused on consumers. Results suggest the need for more efforts on the investigation of corporative responsibility in the way to stop microplastics pollution.


Estimating the burden of illness related to genital warts in the Philippines: a nationally representative cross-sectional study.
This study estimated genital warts prevalence, genital-warts-related healthcare resource use and costs, and self-reported human-papillomavirus-related psychosocial impact among male and female patients aged 18-60 years in the Philippines. Prevalence was estimated using daily logs numbering genital warts patients treated by participating physicians in 4 Philippine regions over a 5-week period (09JUL2011-24SEP2012). Physicians also completed a survey assessing patient referral patterns, healthcare resource use, treatment, and follow-up care. Psychosocial impact was estimated using the human papillomavirus impact profile and the EQ-5D questionnaires. HIP and EQ-5D scores were compared according to the presence of GW (males) and HPV disease (females). CECA scores were also compared by gender and age groups. Overall genital warts prevalence was estimated at 4.78% (95% confidence interval [CI]: 4.58-4.98%) for men and women aged 18-60 years. Genital warts prevalence was 3.39% (95% CI: 3.13-3.65%) and 8.0% (95% CI: 7.69-8.31%) among women and men, respectively. Prevalence estimates were highest in infectious disease specialist practices 18.67% (95% CI: 18.66-18.69%). Two thirds of the 233 (69.14%) male and 166 (67.20%) female patients were newly-diagnosed genital warts cases. Median costs for genital warts diagnosis and treatment reached 7121 and 7000 Philippine pesos among men and women, respectively. In the Cuestionario Específico para Condiloma Acuminado questionnaire, no statistically significant differences between patients were observed. In the EQ-5D questionnaire, male genital warts patients reported lower mean visual analogue scale scores than those without genital warts (78.20 vs 86.34, p < 0.0001). Mean visual analogue scale score values and utility values were lower for women with human-papillomavirus-related diseases than those without (77.98 vs 78.93, and 0.84 vs 0.88, respectively). Genital warts is prevalent in the Philippines; more than 60% of cases were newly diagnosed, contributing to high genital-warts-related healthcare resource costs. Diagnosis of genital warts and human papillomavirus negatively impacted psychosocial indices such as patient well-being and health-related quality of life.


Emory's Winship Earns Comprehensive Status.
Emory University's Winship Cancer Institute in Atlanta, GA, has been granted Comprehensive Cancer Center status, the NCI's highest designation. The center was particularly recognized for its population-based research and extensive clinical trials program.


Fine-root traits in the global spectrum of plant form and function.
Plant traits determine how individual plants cope with heterogeneous environments. Despite large variability in individual traits, trait coordination and trade-offs1,2 result in some trait combinations being much more widespread than others, as revealed in the global spectrum of plant form and function (GSPFF3) and the root economics space (RES4) for aboveground and fine-root traits, respectively. Here we combine the traits that define both functional spaces. Our analysis confirms the major trends of the GSPFF and shows that the RES captures additional information. The four dimensions needed to explain the non-redundant information in the dataset can be summarized in an aboveground and a fine-root plane, corresponding to the GSPFF and the RES, respectively. Both planes display high levels of species aggregation, but the differentiation among growth forms, families and biomes is lower on the fine-root plane, which does not include any size-related trait, than on the aboveground plane. As a result, many species with similar fine-root syndromes display contrasting aboveground traits. This highlights the importance of including belowground organs to the GSPFF when exploring the interplay between different natural selection pressures and whole-plant trait integration.


Evaluating Factors Contributing to Dropout in a Large Peritoneal Dialysis Program.
The low prevalence of peritoneal dialysis (PD) (9%) vs. hemodialysis (HD) (88.2%) is partly due to patient dropout from therapy. This retrospective study identified patients who withdrew from PD between 2016 and 2018 in our program. We evaluated all other factors as controllable losses. Analysis included time on therapy at dropout (very early, early or late) and method of initiation (HD to PD conversion, unplanned PD, or planned start). Eighty-three patients enrolled into our PD program. 27 dropped out; 24 were due to controllable factors, 3 due to death, with a median age at dropout of 52 years old. We determined psychosocial factors (PF) to be the largest controllable factor influencing dropout; contributing a 63% rate among all controllable factors. When considering time until dropout, 100% of very early dropout patients and 50% of late dropout patients did so due to PF. Among early dropout patients 67% dropped out due to other medical reasons. The mean time to dropout for PF, other, and infection (INF) were 13, 26, and 33 months, respectively. When considering type of initiation, we found PF to be the largest attributable factor with 50% of unplanned, 100% of planned, and 50% of conversions stopping therapy. Our study indicates that the primary reason for controllable loss from therapy was secondary to PF regardless of the time on therapy or the method of initiation to therapy.


Syntheses of bioactive bisabolane-type Cryptomeria japonica sesquiterpenes.
The first diastereoselective synthesis of (1S,6R)-1-hydroxy-2,7(14),10-bisabolatrien-4-one, an antifeedant against Acusta despesta and Locusta migratoria, was produced from Cryptomeria japonica (commonly known as Japanese cedar), starting from (R)-(-)-carvone via (R)-(-)-cryptomerione. The enantiomer was transformed into (1S,3R,6R)-1-hydroxy-7(14),10-bisaboladien-4-one, a novel antifeedant against L. migratoria from the same tree, by 1,4-selective reduction of the enone moiety.


The MVQOLI successfully captured quality of life in African palliative care: a factor analysis.
To examine the factor structure of the Missoula Vitas Quality of Life Index (MVQOLI) in palliative care patients in South Africa and Uganda and to assess the tool's appropriateness for measuring quality of life (QOL) in this context. Cross-sectional survey using the MVQOLI, a 26-item QOL measure containing five subscales (Function, Symptoms, Interpersonal, Well being, and Transcendent), in five palliative care services in South Africa and Uganda. Two hundred eighty-five patients were recruited; mean age was 40.1 years; 197 (69.1%) were female; primary diagnoses were human immunodeficiency virus infection (80.7%) and cancer (17.9%). A five-factor solution, accounting for 55% of variance, presented the best model of fit. The factors corresponded relatively closely to the original subscales, with only 4 of the 20 items not loading on the factor corresponding to the appropriate subscale. Internal consistency was high (α=0.83). We found evidence of five factors underpinning the MVQOLI in a large sample of South African and Ugandan palliative care patients. The five factors corresponded reasonably well to the original subscales, suggesting that it is a promising measure for use in this population. However, further testing of its psychometric properties, comprehensibility, and scoring require further research in sub-Saharan Africa.


Trisomy 18 and 18p- features in a case of isochromosome 18q [46,XY,i(18q)]: prenatal diagnosis and autopsy report.
This paper reports the prenatal diagnosis and autopsy findings of a case of true isochromosome 18q [46,XY,i(18q)] with severe cephalic malformations. Comparison is made with other cases of i(18q).


Vaccination of different strains of mice against cutaneous leishmaniosis: usefulness of membrane antigens encapsulated into liposomes by intraperitoneal and subcutaneous administration.
The objective of this study was to assess the usefulness of parasite-surface molecules reconstituted into liposomes to vaccinate four different strains of mice (C57BL/10, CBA/ca, C57BL/6 and NZB) with different levels of susceptibility to L. m. mexicana infection and to find out possible increases in specific antibody response after vaccination, but before infection with virulent promastigotes. Mice were vaccinated with parasite membrane antigens incorporated into liposomes and antibody levels were recorded. Vaccination was effective to protect CBA/ca and C57BL/6 but not C57BL/10 mice and NZB animals were naturally resistant. Intraperitoneal (ip) was more effective than the subcutaneous (sc) route of inoculation, and the induction of disease-resistance correlated with the production of IgG anti-Leishmania in CBA/ca, C57BL/6 and C57BL/10 mice.


Overcoming Barriers to Drug Development in Children with CKD.
Like all sick children, children with CKD need access to safe and effective medicines that have been formulated and examined specifically for them. Despite legislation in the United States and the European Union that either mandates or incentivizes programs for children, conducting trials to advance the treatment of children continues to prove to be a challenge for drug developers. This is also the case for drug development in children with CKD, where trials face challenges in recruitment and completion and where there remains a substantial time lag between initial approval of a medicinal product for use in adults and completion of studies that result in the addition of pediatric-specific labeling for the same indication. The Kidney Health Initiative commissioned a workgroup of diverse stakeholders ( https://khi.asn-online.org/projects/project.aspx?ID=61 ), including participants from the Food and Drug Administration and the European Medicines Agency, to think carefully through the challenges in drug development for children with CKD and how to overcome them. This article provides an overview of the regulatory frameworks in the United States and the European Union that govern pediatric drug development, the current landscape of drug development and approval for children with CKD, the challenges in conduct and execution of these drug trials, and the progress that has been made to facilitate drug development for children with CKD.


Quality of life meta-analysis following coloanal anastomosis versus abdominoperineal resection for low rectal cancer.
In low rectal cancers without sphincter involvement a permanent stoma can be avoided without compromising oncological safety. Functional outcomes following coloanal anastomosis (CAA) compared to abdominoperineal excision (APR) may be significantly different. This study examines all available comparative quality of life (QoL) data for patients undergoing CAA versus APR for low rectal cancer. Published studies with comparative data on QoL outcomes following CAA versus APR for low rectal cancer were extracted from electronic databases. The study was registered with PROSPERO and adhered to PRISMA (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Data was combined using random-effects models. Seven comparative series examined QoL in 527 patients. There was no difference in the numbers receiving neoadjuvant radiotherapy in the APR and CAA groups (OR: 1.19, 95% CI: 0.78-1.81, p = 0.43). CAA was associated with higher mean scores for physical functioning(std mean diff -7.08, 95% CI: -11.92 to -2.25, p = 0.004) and body image (std. mean diff 11.11, 95% CI: 6.04-16.18, p < 0.0001). Male sexual problems were significantly increased in patients who had undergone APR compared to CAA (std. mean diff -16.20, 95% CI: -25.76 to -6.64, p = 0.0009). Patients who had an APR reported more fatigue, dyspnoea and appetite loss. Those who had a CAA reported higher scores for both constipation and diarrhoea. It is reasonable to offer a CAA to motivated patients where oncological outcomes will not be threatened. QoL outcomes appear to be superior when intestinal continuity is maintained, and permanent stoma avoided.


Human annulus fibrosus material properties from biaxial testing and constitutive modeling are altered with degeneration.
The annulus fibrosus (AF) of the intervertebral disk undergoes large and multidirectional stresses and strains. Uniaxial tensile tests are limited for measuring AF material properties, because freely contracting edges can prevent fiber stretch and are not representative of in situ boundary conditions. The objectives of this study were to measure human AF biaxial tensile mechanics and to apply and validate a constitutive model to determine material properties. Biaxial tensile tests were performed on samples oriented along the circumferential-axial and the radial-axial directions. Data were fit to a structurally motivated anisotropic hyperelastic model composed of isotropic extra-fibrillar matrix, nonlinear fibers, and fiber-matrix interactions (FMI) normal to the fibers. The validated model was used to simulate shear and uniaxial tensile behavior, to investigate AF structure-function, and to quantify the effect of degeneration. The biaxial stress-strain response was described well by the model (R (2) > 0.9). The model showed that the parameters for fiber nonlinearity and the normal FMI correlated with degeneration, resulting in an elongated toe-region and lower stiffness with degeneration. The model simulations in shear and uniaxial tension successfully matched previously published circumferential direction Young's modulus, provided an explanation for the low values in previously published axial direction Young's modulus, and was able to simulate shear mechanics. The normal FMI were important contributors to stress and changed with degeneration, therefore, their microstructural and compositional source should be investigated. Finally, the biaxial mechanical data and constitutive model can be incorporated into a disk finite element model to provide improved quantification of disk mechanics.


A monoclonal antibody against a hepatitis B e antigen epitope borne by six amino acids encoded by the precore region.
Hepatitis B e antigen (HBeAg) polypeptide in the circulation (p17e) is composed of ten amino acids (aa) coded for by the precore region and 149 aa by the core gene of hepatitis B virus. A monoclonal antibody (Y0583A) was raised against the N-terminal ten amino acids (SKLCLGWLWG) encoded by the precore region. The binding of Y0583A with a panel of 203 decapeptides on multipins, which covered the precursor of HBeAg polypeptide made of 212 aa shifting by one aa, recognized an epitope sequenced LGWLWG representing the C-terminal six aa coded for by the precore region. This HBeAg epitope was not readily accessible on HBeAg in serum, but it became exposed and bound with Y0583A by treatment with 0.2 N NaOH. Using Y0583A, an enzyme-linked immunosorbent assay was developed for specific determination of HBeAg. The test sample was incubated with the monoclonal antibody to an HBeAg determinant encoded by the core gene (904) that had been immobilized on a solid support. Captured HBeAg was treated with 0.2 N NaOH, neutralized and released into the fluid phase. The reactant was then tested for a sandwich between monoclonal antibody (C33) to the C-terminus of the HBeAg polypeptide immobilized on a solid support and Y0583A labeled with horseradish peroxidase.


The early history of anaesthesia in Newfoundland.
The early history of anaesthesia in Newfoundland is described by reference to newspapers and other writings of the time. News of ether first reached Newfoundland in February 1847 with a report from England of Robert Liston's amputation of a leg on December 21, 1846. Ether was first used in St. John's some days before July 30, 1847, for an operation to amputate both legs, the surgeon being Edward Keilley. Chloroform was used in St. John's a few days before May 4, 1848 by Samuel Carson in an obstetrical case, and on May 10, 1848 it was used during the amputation of a leg by Edward Keilley. Also discussed are some other items of anaesthetic interest which occurred during the years following until the appointment of the first (albeit part-time) anaesthetist in St. John's in 1912.


Risk Factors Related to the Presence of Meniscal Injury and Irreparable Meniscal Tear at Primary Anterior Cruciate Ligament Reconstruction.
Few studies have attempted to identify risk factors associated with irreparable meniscal tears at anterior cruciate ligament reconstruction (ACLR) and to describe follow-up data, such as the failure rate, after meniscal repair. To investigate the associations of age, sex, body mass index (BMI), time to surgery (TTS), and preinjury Tegner score with the presence of meniscal injuries and irreparable meniscal tears at primary ACLR. Cross-sectional study; Level of evidence, 3. A retrospective review was performed on 784 patients who underwent primary ACLR by a single surgeon between 2005 and 2017 (406 men and 378 women; mean age, 25.8 years; mean BMI, 23.1; median TTS, 3 months; median preinjury Tegner score, 7). All patients had a minimum follow-up of 12 months (mean postoperative follow-up, 33.0 months). Multivariate logistic regression analysis was conducted to determine the association of patient variables with the presence of meniscal injuries and irreparable meniscal tears during primary ACLR. The risk factor for medial meniscal injuries was TTS ≥3 months (odds ratio [OR], 4.213; 95% CI, 3.104-5.719; P < .001). The presence of irreparable medial meniscal tears increased with older age (OR, 1.053; 95% CI, 1.024-1.084; P < .001), higher BMI (OR, 1.077; 95% CI, 1.003-1.156; P = .042), and TTS ≥3 months (OR, 1.794; 95% CI, 1.046-3.078; P = .034). On multivariate analysis, none of the variables were significantly associated with lateral meniscal injuries and irreparable meniscal tears. The failure rate, defined as patients who needed additional medial meniscal surgery after medial meniscal repair, was 4.6%. Time from ACL injury to reconstruction of ≥3 months was strongly associated with medial meniscal injuries and irreparable medial meniscal tears at primary ACLR. Older age and increased BMI were also risk factors for the presence of irreparable medial meniscal tears at ACLR.


Construction of energy-conserving sucrose utilization pathways for improving poly-γ-glutamic acid production in Bacillus amyloliquefaciens.
Sucrose is an naturally abundant and easily fermentable feedstock for various biochemical production processes. By now, several sucrose utilization pathways have been identified and characterized. Among them, the pathway consists of sucrose permease and sucrose phosphorylase is an energy-conserving sucrose utilization pathway because it consumes less ATP when comparing to other known pathways. Bacillus amyloliquefaciens NK-1 strain can use sucrose as the feedstock to produce poly-γ-glutamic acid (γ-PGA), a highly valuable biopolymer. The native sucrose utilization pathway in NK-1 strain consists of phosphoenolpyruvate-dependent phosphotransferase system and sucrose-6-P hydrolase and consumes more ATP than the energy-conserving sucrose utilization pathway. In this study, the native sucrose utilization pathway in NK-1 was firstly deleted and generated the B. amyloliquefaciens 3Δ strain. Then four combination of heterologous energy-conserving sucrose utilization pathways were constructed and introduced into the 3Δ strain. Results demonstrated that the combination of cscB (encodes sucrose permease) from Escherichia coli and sucP (encodes sucrose phosphorylase) from Bifidobacterium adolescentis showed the highest sucrose metabolic efficiency. The corresponding mutant consumed 49.4% more sucrose and produced 38.5% more γ-PGA than the NK-1 strain under the same fermentation conditions. To our best knowledge, this is the first report concerning the enhancement of the target product production by introducing the heterologous energy-conserving sucrose utilization pathways. Such a strategy can be easily extended to other microorganism hosts for reinforced biochemical production using sucrose as substrate.


Smart spectrophotometric methods for stability assessment of two co-formulated antigout drugs.
Simple, sensitive and accurate stability indicating spectrophotometric methods have been developed for the simultaneous determination of probenecid, colchicine as well as colchicine degradation product in their ternary mixture. Probenecid was firstly assayed using the double divisor ratio spectra derivative method. On the other hand, three spectrophotometric methods, namely: ratio difference, derivative ratio and mean centering of ratio spectra, have been suggested for the simultaneous quantification of colchicine and its degradation product. The obtained calibration curves were linear at 2.5-30.0 μg/mL, 0.5-25.0 μg/mL and 1.0-13.0 μg/mL for probenecid, colchicine and colchicine degradation product, respectively. The investigated methods were validated in accordance with the International Council for Harmonisation guidelines and were effectively used for quantification of probenecid and colchicine in their bulk powders and combined pharmaceutical dosage form.


Reproductive history, infertility treatment, and the risk of acute leukemia in children with down syndrome: a report from the Children's Oncology Group.
Children with Down syndrome (DS) have from 10 to 20 times the risk of developing acute leukemia than the general pediatric population. There is mixed evidence for associations between reproductive history or infertility and acute leukemia among children without DS. The authors conducted a case-control study of acute leukemia among children with DS to investigate possible risk factors in this population. From 1997 to 2002, 158 children aged <20 years with DS who had a diagnosis of acute leukemia (97 children with acute lymphoblastic leukemia [ALL] and 61 children with acute myeloid leukemia [AML]) were enrolled at Children's Oncology Group (COG) institutions. Controls with DS (n = 173) were selected from the cases' primary care clinic and frequency matched to cases on age. Telephone interviews were conducted with mothers of cases and controls assessing reproductive history, infertility, and infertility treatment. Null results were observed overall and by subtype for reproductive factors, including previous pregnancy outcomes and contraceptive use, and for most infertility outcomes. There was an increased risk of AML among children with DS whose parents had ever tried for >/=1 year to become pregnant (odds ratio [OR], 2.22; 95% confidence interval [95% CI], 1.14-4.33). A 1-year increase in maternal age also was associated with AML (OR, 1.06; 95% CI, 1.01-1.12). Although the questionnaire was limited in this area, the results suggested that the risk for AML may be raised in children with DS because of infertility. In that the risk of infertility, along with having a child with DS, increase with age, these results warrant more research.


A correlation of pregnancy term, disease activity, serum female hormones, and cytokines in uveitis.
Pregnancy and the postpartum period are associated with the activity of autoimmune diseases including uveitis. Although the exact mechanism is unknown, hormones are reported to alter inflammatory cytokines and influence disease activity. The authors studied ocular inflammation, female hormones, and serum cytokine levels during and after pregnancy. A prospective, observational case study was conducted. Four pregnant women in their first trimester with chronic non-infectious uveitis were followed monthly until 6 months after delivery. Serum female hormones (oestrogen, progesterone, prolactin) and various cytokines (IL-2, IL-4, IL-5, IL-6, IL-10, IFN-gamma, and TGF-beta) were measured by ELISA. The four patients had five full term pregnancies. Uveitis activity decreased after the first trimester but flared in the early postpartum period. Serum female hormones, highly elevated during pregnancy, drastically dropped post partum. Cytokine levels except TGF-beta were mostly undetectable. Female hormones and TGF-beta may contribute to the activity of uveitis during pregnancy and the postpartum period.


The "liver-first approach" for patients with locally advanced rectal cancer and synchronous liver metastases.
This study was designed to investigate the outcome of "the liver-first" approach in patients with locally advanced rectal cancer and synchronous liver metastases. Patients with locally advanced rectal cancer and synchronous liver metastases were primarily treated for their liver metastases. If successful, patients underwent treatment for the rectal tumor. Twenty-three patients were included. One patient had liver resection without neoadjuvant chemotherapy followed by chemoradiotherapy. All remaining 22 patients underwent laparotomy after chemotherapy. Eighteen patients underwent partial liver resection and subsequent chemoradiotherapy for the rectal cancer. One patient underwent in one session a partial liver resection and a low anterior resection. Six patients were not treated according to protocol because of extensive disease. Sixteen patients (73 percent) completed the full treatment protocol and all are alive after a median period of 19 (range, 7-56) months. This is the first sizable report on the "liver-first approach" demonstrating that it may be considered the preferred treatment schedule for patients with locally advanced rectal cancer and synchronous liver metastases. It allows most patients to undergo curative resections of both metastatic and primary disease and can avoid useless rectal surgery in patients with incurable metastatic disease.


Strategies for block-design fMRI experiments during task-related motion of structures of the oral cavity.
Functional MRI (fMRI) studies of jaw motion, speech, and swallowing disorders have been hampered by motion artifacts. Tissue motion perturbs the static magnetic field, creating geometric distortions in echo-planar images that lead to many false positives in activation maps. These problems have restricted blood oxygenation level-dependent (BOLD) fMRI studies involving orofacial muscles to event-related designs, which offer weak contrast-to-noise ratios when compared to block designs. Two new approaches are described that greatly reduce false positives in the activation maps created by the distortions in block-design fMRI studies involving jaw and tongue motion during chewing. First, an appropriate task duration of 10-14 s was found to maximize functional contrast while minimizing motion artifacts. Second, three motion-sensitive postprocessing methods were applied successively to examine the temporal and spatial characteristics of responses and identify and remove false positives caused by motion artifacts. These techniques are shown to allow the use of block design in an fMRI study of a jaw motion task. Extension to speech and swallowing tasks is discussed.


Radiolucent Lesions of the Jaws: An Attempted Demonstration of the Use of Co-Word Analysis to List Main Similar Pathologies.
(1) Background: Many radiolucent jaw lesions exist, and they often show a radiographic resemblance, rendering diagnosis a challenging act. Closely related lesions should be frequently mentioned together in the academic literature, which might be helpful for junior practitioners in determining their differential diagnosis. The usefulness of bibliometric analysis in this respect has yet to be demonstrated. (2) Methods: This study evaluated academic publications on radiolucent jaw lesions, as indexed by the Web of Science Core Collection database. The mentions of radiolucent jaw lesions were extracted from the complete bibliographic records of the publications, and co-word analyses were conducted with the aid of VOSviewer. (3) Results: Based on 1897 papers, visualization maps were synthesized to evaluate co-occurrences of the radiolucent jaw lesions. Ameloblastoma was frequently mentioned together with odontogenic keratocyst, dentigerous cyst, and radicular cyst. Osseous dysplasia was co-mentioned with osteomyelitis, ossifying fibroma, odontoma, fibrous dysplasia, and apical periodontitis. (4) Conclusions: The co-word analysis, a form of bibliometric analysis, could demonstrate a relatedness of radiolucent jaw lesions that could be considered at differential diagnosis.


Cochlear implantation in children with cochlear malformations.
To address the surgical and habilitative issues raised by cochlear implantation in children with cochlear dysplasia. The English-language literature is reviewed and the New York University Medical Center experience with three patients is detailed. Two hundred institutions performing cochlear implants were queried by questionnaire. Hospitals performing cochlear implantation. Pediatric patients with a cochlear implant in an ear with a dysplastic cochlea. Preoperative computed tomography analysis of cochlear anatomy was compared with operative findings, complications, and postoperative device use. Facial nerve anatomy was anomalous in 16% of patients, and there were two surgical injuries. There were no cases of meningitis. All patients who received multichannel implants derive benefit and wear their devices. All degrees of cochlear dysplasia, ranging from incomplete partition to common cavity, can be safely implanted and auditory responses expected.


Molecular masses and sedimentation coefficients of extracellular hemoglobin of Glossoscolex paulistus: alkaline oligomeric dissociation.
The giant extracellular hemoglobin of Glossoscolex paulistus (HbGp) has a molecular mass (M) of 3600±100 kDa and a standard sedimentation coefficient (s20,w0) of 58 S, estimated by analytical ultracentrifugation (AUC). In the present work, further AUC studies were developed for HbGp, at pH 10.0, which favors oligomeric dissociation into lower M species. The HbGp oligomer is formed by globin chains a, b, c and d plus the linker chains. The pure monomeric fraction, subunit d, and HbGp at pH 10.0, in the presence of β-mercaptoethanol, were also studied. Our results indicate that for samples of pure subunit d, besides the monomeric species with s20,w0 of 2.0 S, formation of dimer of subunit d is observed with s20,w0 of around 2.9 S. For the whole HbGp at pH 10.0 contributions from monomers, trimers and linkers are observed. No contribution from 58 S species was observed for the sample of oxy-HbGp at pH 10.0, showing its complete dissociation. For cyanomet-HbGp form a contribution of 17% is observed for the un-dissociated oligomer, consistent with data from other techniques that show the cyanomet-form is more stable as compared to oxy-HbGp. Masses of HbGp subunits, especially trimer abc and monomeric chains a, b, c and d, were also estimated from sedimentation equilibrium data, and are in agreement with the results from MALDI-TOF-MS.


Nanogels for regenerative medicine.
Nanogels have been widely explored for drug delivery, but their applications in the tissue engineering field are still quite recent. Regenerative medicine also demands controlled delivery of growth factors and other active substances able to promote cell adhesion and guide cell differentiation and tissue formation. Moreover, nanogels could be added to tissue scaffolds for modifying their inner architecture, texture and mechanical properties, which are critical for regulating cell behavior. This review aims to provide an insight into the different roles that nanogels may play for improving tissue regeneration. Last decade literature has been carefully analyzed with a focus on in vivo outcomes. After an introductory section to nanogels, relevant examples of their performance for skin and bone tissue regeneration applications are discussed. Healing of chronic wounds and critical size bone fractures may significantly improve thanks to the use of nanogels solely or in combination with scaffolds. Nanogel roles in regenerating vessels, cardiac tissue, urothelium and urethral muscle tissue are also presented. Overall, the information gathered in the review clearly highlights the relevance of multidisciplinary approaches to design nanogels that can face up to the needs of the regenerative medicine. Nanogels may help bring together researchers working in active ingredient formulation, controlled release, nanomechanics, tissue engineering and scaffolding with the common purpose of developing clinically relevant tools for the complete regeneration of complex tissues.


Timeline of Intestinal Adaptation After Malabsortive Surgery: Effect of Luminal Nutrients, Biliopancreatic Secretion, and Glutamine Supplementation.
The aim of this study was to study the process of intestinal adaptation in the three limbs of the small intestine after malabsorptive bariatric surgery: the biliopancreatic limb, the alimentary limb, and the common channel. These limbs are exposed to different stimuli, namely, gastrointestinal transit and nutrients in the alimentary limb, biliopancreatic secretions in the biliopancreatic limb, and a mix of both in the common channel. We also wished to investigate the effect of glutamine supplementation on the adaptation process. Three types of surgery were performed using a porcine model: biliopancreatic bypass (BPBP), massive (75%) short bowel resection as the positive control, and a sham operation (transection) as the negative control. We measured the height and width of intestinal villi, histidine decarboxylase (HDC) activity, and amount of HDC messenger RNA (mRNA) (standard diet or a diet supplemented with glutamine). An increase in HDC activity and mRNA expression was observed in the BPBP group. This increase coincided with an increase in the height and width of the intestinal villi. The increase in villus height was observed immediately after surgery and peaked at 2 weeks. Levels remained higher than those observed in sham-operated pigs for a further 4 weeks. The intestinal adaptation process in animals that underwent BPBP was less intense than in those that underwent massive short bowel resection and more intense than in those that underwent transection only. Supplementation with glutamine did not improve any of the parameters studied, although it did appear to accelerate the adaptive process.


Influence of low corrected seminal fructose levels on sperm chromatin stability in semen from men attending an infertility service.
To determine any correlation between sperm chromatin stability under sodium dodecyl sulfate (SDS), and SDS-ethylendiamine tetraacetic acid (SDS and EDTA) conditions with levels of corrected seminal fructose, obtained multiplying logarithm of sperm count by seminal fructose concentration, in men attending an infertility service. Cross sectional study to compare semen parameters of two groups (control and experimental), one with normal levels of corrected fructose (control) and the second with low levels of corrected fructose (experimental). Subjects were also grouped according to number, motility and morphology of sperm, and according to results of hypo-osmotic test. Andrology laboratory at the Instituto de Investigaciones de la Altura, Lima, Perú. Two hundred and twenty five male partners in infertile couples attending the Andrology Laboratory. None semen analysis, hypo-osmotic swelling test, sperm chromatin stability after SDS, and SDS and EDTA, and seminal fructose. Seminal volume, sperm motility, and seminal fructose were significantly lower in samples from subjects with low levels of corrected fructose. Subjects with low levels of corrected fructose had also high sperm chromatin stability under SDS, and SDS and EDTA treatment. After SDS treatment, sperm chromatin stability was similar in normal samples and in those with oligozoospermia, asthenozoospermia, teratozoospermia, or abnormal hypo-osmotic swelling test. After SDS and EDTA treatment, a high sperm stability was observed in samples with asthenozoospermia. This hyper-stability is observed in asthenozoospermic samples with low corrected fructose levels, but not in asthenozoospermic samples with normal corrected fructose levels. The logistic regression analysis applied to asthenozoospermic data showed that chronological age, seminal volume, acid phosphatase per ejaculate and percent of stable sperm after SDS and EDTA treatment were significantly associated to levels of corrected fructose. Low levels of corrected fructose were associated to low seminal volume, low sperm motility, and high sperm chromatin stability under SDS and EDTA treatment.


Hospital-based prevalence of high-risk cervical HPV types infecting the general population and female sex workers in Huzhou, China.
To evaluate the prevalence of high-risk HPV types among female sex workers and the general population in Huzhou, China. Cervical samples from the general population (n=292) and female sex workers (n=288) in Huzhou, China, were collected between April, 2008, and October, 2009. Demographic, behavioral, and clinical data were obtained by interview. Genotyping of the HPV L1 gene was done via a PGMY09/PGMY11 PCR-based assay, and the cervical samples were subjected to cytology analysis. The prevalence of HPV was higher among female sex workers (66.7%) than among the general population (19.2%). Among female sex workers, HPV-16 (28.8%) was the most prevalent, followed by HPV-58 (24.0%) and HPV-52 (20.8%). The percentage of cervical abnormalities was higher among female sex workers (20.8%) than among the general population (4.8%). Multivariate analysis showed that education level and condom use during coitus were significantly associated with HPV infection (P<0.05). HPV-16, HPV-58 and HPV-52 were the dominant types, and were significantly associated with abnormal cervical cytology (P<0.05). Female sex workers in Huzhou, China, were found to have a greater probability of being infected with high-risk HPV, and novel vaccines against HPV-58 and HPV-52 should be developed. Using condoms could reduce the risk of infection.


Breastfeeding practices in women with type 1 diabetes: a discussion of the psychosocial factors and policies in Sweden and Australia.
Women with type 1 diabetes (T1DM) face many challenges during their pregnancy, birth and in the postnatal period, including breastfeeding initiation and continuation while maintaining stable glycaemic control. In both Sweden and Australia the rates of breastfeeding initiation are high. However, overall there is limited information about the breastfeeding practices of women with T1DM and the factors affecting them. Similarities in demographics, birth rates and health systems create bases for discussion. The aim of this paper is to discuss psychosocial factors, policies and practices that impact on the breastfeeding practices of women with T1DM. Swedish research indicates that the overall breastfeeding rate in women with T1DM remains significantly lower than in women without diabetes in the first 2 and 6 months after childbirth with no differences in exclusive breastfeeding. Breastfeeding initiation and continuation among women with T1DM in Sweden has been shown to be influenced by health services delivery, supportive breastfeeding policies and socio-economic factors, particular perceived support from social networks and health professionals. There is limited research on the impact of attitudes towards breastfeeding, emotional and social well-being and diabetes-related stress on the decision of women with T1DM to initiate and continue to breastfeed for at least 6 months. A more comprehensive understanding of the breastfeeding practices and psychosocial factors operating during the first 6 months after birth for women with T1DM will be instrumental in the future design of interventions promoting initiation and continuation of breastfeeding in Sweden, Australia and elsewhere.


Depressive symptoms and health-related quality of life in a heterogeneous psychiatric sample: conditional indirect effects of pain severity and interference.
Few studies have examined clinically relevant mechanisms that underlie the association between two important indices of recovery- depression severity and health-related quality of life (HRQOL) in psychiatric outpatients. This study aimed to explicate the roles of pain interference and pain severity as mediating and moderating mechanisms in the relationship between depressive symptoms and HRQOL. Data from 290 outpatients diagnosed with schizophrenia (n = 102), depressive (n = 98), and anxiety (n = 90) disorders were examined. Participants completed a set of questionnaires that queried their sociodemographic statuses, current pain severity and interference levels, depression severity levels, and HRQOL. Subsequently, mediation and moderation analyses were conducted. Analyses revealed that pain interference fully mediated the relationship between depressive symptoms and physical (34% of the total effect) but not mental HRQOL. At high pain levels (+ 1 SD from mean), depressive symptoms may interfere with physical quality of life through pain interference, but this was not present at low pain levels (- 1 SD from mean). Prolonged pain symptoms could negatively influence psychiatric recovery beyond the physical aspect of HRQOL. These results thus imply a need to detect and manage severe physical pain complaints at the acute stage in psychiatric outpatients.


Corrigendum: Populus trichocarpa PtNF-YA9, a Multifunctional Transcription Factor, Regulates Seed Germination, Abiotic Stress, Plant Growth and Development in Arabidopsis.
[This corrects the article DOI: 10.3389/fpls.2018.00954.].


Building coalitions: A statewide nursing organization's role in changing nursing education regulation during the COVID-19 pandemic.
The California Association of Colleges of Nursing (CACN), representing California's baccalaureate and higher degree nursing education programs, has raised concerns for over two-years about the number, relevance, and legitimacy of nursing education regulations. Formal CACN letters to state regulators did not affect change. While California nursing education regulations require 75% direct patient contact for all clinical courses, meeting this requirement became impossible as clinical agencies closed to nursing students during the beginning of the COVID-19 pandemic. Nursing regulatory change was urgently needed to provide greater flexibility in meeting clinical course objectives using simulation and other online learning modalities. At stake was the graduation of over 14,971 RN students from public and private nursing programs. While state regulators opposed a legislative approach, CACN collaborated with stakeholders to support legislation that led to a reduction in direct patient care hours, allowing nursing students to progress and graduate. This longstanding advocacy work was accelerated by the pandemic and required leadership and knowledge about the legislative process for nurse educators to succeed. The ultimate goal for CACN is to forge a more respectful relationship and greater collaboration between educators and regulators to enhance quality, reduce costs, and redundancies in nursing education in this state.


Combined approach of perioperative 18F-FDG PET/CT imaging and intraoperative 18F-FDG handheld gamma probe detection for tumor localization and verification of complete tumor resection in breast cancer.
18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has become an established method for detecting hypermetabolic sites of known and occult disease and is widely used in oncology surgical planning. Intraoperatively, it is often difficult to localize tumors and verify complete resection of tumors that have been previously detected on diagnostic PET/CT at the time of the original evaluation of the cancer patient. Therefore, we propose an innovative approach for intraoperative tumor localization and verification of complete tumor resection utilizing 18F-FDG for perioperative PET/CT imaging and intraoperative gamma probe detection. Two breast cancer patients were evaluated. 18F-FDG was administered and PET/CT was acquired immediately prior to surgery. Intraoperatively, tumors were localized and resected with the assistance of a handheld gamma probe. Resected tumors were scanned with specimen PET/CT prior to pathologic processing. Shortly after the surgical procedure, patients were re-imaged with PET/CT utilizing the same preoperatively administered 18F-FDG dose. One patient had primary carcinoma of breast and a metastatic axillary lymph node. The second patient had a solitary metastatic liver lesion. In both cases, preoperative PET/CT verified these findings and demonstrated no additional suspicious hypermetabolic lesions. Furthermore, intraoperative gamma probe detection, specimen PET/CT, and postoperative PET/CT verified complete resection of the hypermetabolic lesions. Immediate preoperative and postoperative PET/CT imaging, utilizing the same 18F-FDG injection dose, is feasible and image quality is acceptable. Such perioperative PET/CT imaging, along with intraoperative gamma probe detection and specimen PET/CT, can be used to verify complete tumor resection. This innovative approach demonstrates promise for assisting the oncologic surgeon in localizing and verifying resection of 18F-FDG positive tumors and may ultimately positively impact upon long-term patient outcomes.


Mutations in matrix protein 1 and nucleoprotein caused human-specific defects in nuclear exportation and viral assembly of an avian influenza H7N1 virus.
Nuclear exportation of influenza ribonucleoprotein is a vital step in viral replication cycle. In this study a particular H7N1 (A/ostrich/Zimbabwe/222-E3/1996) virus showed exclusively nuclear localization of the viral nucleoprotein (NP) only in human cell lines but not in cell lines of other species suggesting a human-specific nuclear exportation defect. After 10 passages in human lung cells, an adapted strain (H7N1:P10) could efficiently replicate and export viral NP in human cells. Mutations in the NP and matrix M1 gene at position 297 and 227, respectively, were found to rescue the defect. While the NP mutant showed a comparable ratio of total to NP-associated negative-sense RNA in the cytoplasm as compared to the wild type, the M1 mutant showed an increase in free negative-sense RNA in the cytoplasm. These indicated that the NP mutation might cause a nuclear export defect, whereas the M1 mutation might cause a defect in ribonucleoprotein assembly step.


Voltage-dependent lipid flip-flop induced by alamethicin.
Alamethicin appears to allow voltage-dependent lipid exchange ("flip-flop") between leaflets of a planar bilayer. In membranes with one leaflet of phosphatidyl serine and one of phosphatidyl ethanolamine, the shape of the nonactin current-voltage curve accurately reports the difference in surface potential between the two sides of the membrane. The surface potential is itself a good measure of membrane asymmetry. Alamethicin added to the bathing solutions of an asymmetric membrane does not per se reduce the membrane asymmetry, but turning on the alamethicin conductance by application of a voltage pulse does. Immediately after application of a voltage pulse, large enough to turn on the alamethicin conductance, the asymmetry of the nonactin-K+ current voltage curve decreases, in some cases, nearly to zero. During the pulse, the alamethicin conductance activates if a decrease in surface potential favors turn-on of the alamethicin conductance or inactivates if a decrease in surface potential favors turn-off of the alamethicin conductance. After the pulse, the nonactin-K+ asymmetry returns to its original value if the alamethicin conductance is not turned on. The time-course of this return allows an estimate of the diffusion constant of lipid in the planar bilayer. The value obtained is 5.1 x 10(-8) cm2/s.


(3-Aminopropyl)triethoxysilane and iron rice straw biochar composites for the sorption of Cr (VI) and Zn (II) using the extract of heavy metals contaminated soil.
Heavy metals like Cr (VI), when released into the environment, pose a serious threat to animal and human health. In this study, iron and (3-Aminopropyl)triethoxysilane (APTES) biochar composites were prepared from the biochar, which was produced through the pyrolysis of rice straw at 400 and 600 °C, using the chemical processes with an aim that the doping of pristine biochar structure with the Fe and NH2 radicals would enhance the removal of Cr (VI) and Zn (II) adsorption in both aqueous solution and soil. Both biochar composites were mixed at a rate of 3% (w/w) with the mine soil for the soil incubation test, and after completion of the test, a soil fertility index (SFI) was calculated. Results showed that both iron and APTES biochar composites followed the Langmuir-Freundlich isotherm showing the maximum removal capacity of 100.59 mg/g for Cr (VI) by APTES/SiBC 600 and maximum adsorption capacity of 83.92 mg/g for Zn2+ by Fe/BC 400. The SFI of the mine-soil amended with both Fe and APTES biochar composites were 16.67 and 13.04%, respectively higher than the controlled study. The mitotic index of the A. cepa cells that grew up in the soil amended with Fe/BC and APTES/SiBC were 40.47 and 44.45%, respectively, higher than the controlled study. The results indicated that the incorporation of the Fe and APTES biochar composites in the soil effectively reduced the metal toxicity and improved the soil physicochemical properties. This study opens up the prospects of using biochar composites in contaminated soil and water treatments.


Modulating sarco(endo)plasmic reticulum Ca2+ ATPase 2 (SERCA2) activity: cell biological implications.
Of the three mammalian members belonging to the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) family, SERCA2 is evolutionary the oldest and shows the most wide tissue-expression pattern. Two major SERCA2 splice variants are well-characterized: the muscle-specific isoform SERCA2a and the housekeeping isoform SERCA2b. Recently, several interacting proteins and post-translational modifications of SERCA2 were identified which may modulate the activity of the Ca2+ pump. This review aims to give an overview of the vast literature concerning the cell biological implications of the SERCA2 isoform diversity and the factors regulating SERCA2. Proteins reported to interact with SERCA2 from the cytosolic domain involve the anti-apoptotic Bcl-2, the insulin receptor substrates IRS1/2, the EF-hand Ca2+-binding protein S100A1 and acylphosphatase. We will focus on the very particular position of SERCA2 as an enzyme functioning in a thin, highly fluid, leaky and cholesterol-poor membrane. Possible differential interactions of SERCA2b and SERCA2a with calreticulin, calnexin and ERp57, which could occur within the lumen of the endoplasmic reticulum will be discussed. Reported post-translational modifications possibly affecting pump activity involve N-glycosylation, glutathionylation and Ca2+/calmodulin kinase II-dependent phosphorylation. Finally, the pronounced vulnerability to oxidative damage of SERCA2 appears to be pivotal in the etiology of various pathologies.


The role of bacterial biofilm in persistent infections and control strategies.
Bacterial biofilms can be viewed as a specific type of persistent bacterial infection. After initial invasion, microbes can attach to living and non-living surfaces, such as prosthetics and indwelling medical devices, and form a biofilm composed of extracellular polysaccharides, proteins, and other components. In hosts, biofilm formation may trigger drug resistance and inflammation, resulting in persistent infections. The clinical aspects of biofilm formation and leading strategies for biofilm inhibitors will be discussed in this mini-review.


What is the onset mechanism of internal hernia after vertebral body fracture? A case of internal hernia secondary to traumatic vertebral fracture.
A 67-year-old man who had been pinned between a basket crane and a tree complained of severe pain in his lower back and a decreased appetite. Laparotomy after decompressing the gastrointestinal tract revealed incarceration of an ileal loop within a fractured third lumbar vertebra. The damaged bowel was resected, and an end-to-end anastomosis was performed. Once the patient's condition had stabilised, posterior lumbar fixation was performed. There were no abdominal complications or lower limb neurological deficits during the follow-up period. Enhanced CT and MRI had been helpful in making the diagnoses. Histopathological examination revealed the aetiology of the traumatic incarceration: the intestine had been pinched as the disc space closed, and the body attempted to return to its original state by exerting countertraction.


Use of a Locking Plate and Drill Sleeves to Guide Dome-Shaped Supramalleolar Osteotomy: Technique Tip.
Level of Evidence: Level V, expert opinion.


Nuts: anti-atherogenic food?
The prevalence of cardiovascular disease as the leading cause of morbidity and mortality is increasing worldwide. This fact is mainly attributed to the modern lifestyle with predominant characteristics the change of dietary habits and the reduced physical activity which lead to metabolic disorders such as obesity and diabetes. Therefore, drastic dietary interventions are considered necessary in order to reduce cardiovascular risk. Nuts, as a nutritional component have drawn particular attention, due to their beneficial cardiovascular properties derived from their nutrient composition. This is a comprehensive review concerning the potential general effects of nuts. It includes data from older large epidemiologic studies as well as recent significant information from clinical trials regarding this topic. All studies conclude that nuts can play an important role as part of a healthy diet in order to minimize cardiovascular risk and obtain multiple health benefits.


Serum substance P and calcitonin gene-related peptide levels in Behçet's disease and their association with disease activity.
Substance P (SP) and calcitonin gene-related peptide (CGRP) are neuropeptides that have a role in several cutaneous diseases and inflammations. Aim. To evaluate SP, CGRP and serum interleukin (IL)-8 levels in Behçet's disease (BD) and to explore the relationship of these peptides with BD activity. The study group comprised 30 patients with BD, and 30 healthy individuals acted as controls. Serum levels of SP, CGRP and IL-8 were determined by micro-ELISA test during the active and inactive disease periods of patients with BD. These data were compared with each other and controls. Active and inactive periods of BD were established. The mean +/- SD serum CGRP (ng/ml) and IL-8 levels (pg/ml) in inactive BD (5.87 +/- 2.49 and 0.62 +/- 0.24, respectively) were significantly higher than the control group (4.74 +/- 1.17 and 0.46 +/- 0.11) (P < 0.05 for both). The difference between serum CGRP and IL-8 levels in active BD were also significantly higher than in inactive BD (P < 0.05 for both). Serum SP values (ng/ml) in active BD (18.27 +/- 5.38) were significantly higher than in inactive BD (15.26 +/- 5.74) and controls (12.6 +/- 4.45) (P < 0.05 for all), whereas the difference between the serum SP values in inactive BD and the control group was not statistically significant (P > 0.05). Serum SP and CGRP may have a role in the pathogenesis of BD. In addition, serum IL-8, SP and CGRP levels can be used as laboratory parameters indicating activity in BD.


Ciliated protozoan occurrence and association in the pathogenesis of coral disease.
Various microbial infections have significantly contributed to disease progression leading to the mortality of corals. However, the holobiont and the external surfaces of coral, including the secreted mucus, provide a varied microenvironment that attracts ciliates based on their feeding preferences. Besides, some ciliates (e.g., Philasterine scuticociliate) may enter through the injuries or lesions on corals or through their indirect interactions with other types of microbes that influence coral health. Thus, ciliates occurrence and association are described with 12 different diseases worldwide. White syndrome disease lesions have diverse ciliate associations, and higher ciliate diversity was observed with diseased genera Acropora. Also, it was described, about sixteen ciliate species ingest coral Symbiodiniaceae and histophagous ciliates for coral tissue loss as secondary invaders. However, the ciliates nature of association with the coral disease remains unclear for primary or opportunistic secondary pathogenicity. Herein, we explore the urgent need to understand the complex interactions of ciliates in coral health.


Soil management enhancing hydrocarbon biodegradation in the polluted Kuwaiti desert.
Oil-polluted Kuwaiti desert samples, exposed to the open air, were subjected to specific types of management, once every 2 weeks, throughout a year; control samples were not treated. The total amounts of extractable alkanes from the control samples remained fairly constant during the dry hot months, but decreased during the rainy months reaching, after 1 year, slightly more than one-half of the amount at zero time. This result demonstrates the self-cleaning of the Kuwaiti desert and the essential role of moisture in this process. Out of the eight types of management studied, the repeated fertilization of the polluted sample with 3% KNO3 solution was most efficient, reducing the extractable alkanes after 1 year to about one-third of zero reading. Repeated fertilization with treated sewage effluent was inhibitory to alkane biodegradation, probably because of increasing soil acidity. The latter inhibitory effect was annulled by liming. Repeated irrigation with 3% NaCl solution was inhibitory, but 1% NaCl solution slightly promoted alkane biodegradation. The various samples contained 10(10)-10(11) oil-utilizing bacteria/g soil, predominantly Bacillus, Pseudomonas, Rhodococcus and Streptomyces. Oil-utilizing fungi were much less frequent and were predominantly Aspergillus and Penicillium species. The microbial numbers varied not only according to the type of soil management but also to the season.


Low-dose aspirin therapy and placental pathology in women with poor prior pregnancy outcomes.
To determine if low dose aspirin therapy improves placental histology in women with a prior complicated pregnancy demonstrating uterine vascular pathology. A retrospective chart review identified patients with a prior complicated pregnancy with placental changes showing uterine vascular pathology (control pregnancy, CP). In the treated pregnancy (TP), 81 mg/day of ASA was started prior to 10 weeks. Placental reports from the CP and TP were reviewed. Pregnancy outcomes and placental histology from the CP were compared to the TP for each patient. Thirteen patients were enrolled. The majority of patients (8/13, 61.5%) exhibited recurrent, histologic evidence of uterine vascular pathology in the TP. The TP was more likely to be uncomplicated (P < 0.05), delivered after 36 weeks (P < 0.05), and result in the delivery of a viable infant (P < 0.05) compared to the CP. Despite an improvement in outcomes in the aspirin treated pregnancy, histologic evidence of uterine vascular pathology persisted in the majority of women with a prior complicated pregnancy demonstrating similar placental lesions. Abnormal placental histology may be useful in identifying a group of women with poor obstetrical histories who could benefit from low-dose aspirin therapy.


An optimized derivative of an endogenous CXCR4 antagonist prevents atopic dermatitis and airway inflammation.
Aberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes such as cancer and inflammatory diseases. A natural fragment of serum albumin, named EPI-X4, has previously been identified as endogenous peptide antagonist and inverse agonist of CXCR4 and is a promising compound for the development of improved analogues for the therapy of CXCR4-associated diseases. To generate optimized EPI-X4 derivatives we here performed molecular docking analysis to identify key interaction motifs of EPI-X4/CXCR4. Subsequent rational drug design allowed to increase the anti-CXCR4 activity of EPI-X4. The EPI-X4 derivative JM#21 bound CXCR4 and suppressed CXCR4-tropic HIV-1 infection more efficiently than the clinically approved small molecule CXCR4 antagonist AMD3100. EPI-X4 JM#21 did not exert toxic effects in zebrafish embryos and suppressed allergen-induced infiltration of eosinophils and other immune cells into the airways of animals in an asthma mouse model. Moreover, topical administration of the optimized EPI-X4 derivative efficiently prevented inflammation of the skin in a mouse model of atopic dermatitis. Thus, rationally designed EPI-X4 JM#21 is a novel potent antagonist of CXCR4 and the first CXCR4 inhibitor with therapeutic efficacy in atopic dermatitis. Further clinical development of this new class of CXCR4 antagonists for the therapy of atopic dermatitis, asthma and other CXCR4-associated diseases is highly warranted.


The antibacterial activity of fluoroquinolone derivatives: An update (2018-2021).
Bacterial infection is amongst the most common diseases in community and hospital settings. Fluoroquinolones, exerting the antibacterial activity through binding to type II bacterial topoisomerase enzymes, DNA gyrase and topoisomerase IV, are mainstays of chemotherapy. At present, fluoroquinolones are the most valuable antibacterial agents used popularly. However, the emergence of more virulent and resistant pathogens by the development of either mutated DNA-binding proteins or efflux pump mechanism for fluoroquinolones results in an urgent demand to develop new fluoroquinolones to withstand the drug resistance and to obtain a broader spectrum of activity. This review aims to outline the recent advances of fluoroquinolone derivatives with antibacterial potential and to summarize the structure-activity relationship (SAR) so as to provide an insight for rational design of more active candidates, covering articles published between January 2018 and June 2021.


Poorer survival outcomes for male breast cancer compared with female breast cancer may be attributable to in-stage migration.
Male breast cancer accounts for less than 1% of all breast cancers, yet males have a worse prognosis than females with breast cancer. Using the 1988-2003 Surveillance, Epidemiology, and End Results Program data, we conducted a retrospective, population-based cohort study to investigate stage-specific differences in breast cancer-specific and all-cause mortality between males and females. We calculated adjusted hazard ratios (aHR) and 95% confidence intervals (CI) using Cox regression models to compare breast cancer-specific and all-cause mortality by stage between males and females, controlling for potential confounding variables. There were 246,059 patients with a first, single, primary breast cancer [1,541 (0.6%) male; 244,518 (99.4%) female]. Compared with females, males were more likely to be older, Black, married, diagnosed at more advanced stages, and treated with mastectomy (each P < 0.001). Males also were more likely to have lower grade and estrogen/progesterone receptor-positive tumors (each P < 0.001). After controlling for confounders, males were more likely to die from their breast cancer when compared with females, only if diagnosed with stage I disease (aHR 1.72, CI 1.15-2.61). For all-cause mortality, males were more likely than females to die at each stage of disease except stage IV. Although all-cause mortality was higher for men than women at all stages of nonmetastatic breast cancer, higher male breast cancer-specific mortality was attributed to poorer survival in stage I disease. However, this statistical difference is unlikely to be clinically relevant and attributable to in-stage migration.


Retinofugal and retinopetal connections in the upside-down catfish (synodontis nigriventris).
The retinofugal and retinopetal connections in the upside-down catfish Synodontis nigriventris were studied by use of the horseradish-peroxidase (HRP) techniques, autoradiography, and degeneration-silver methods. An unusual retinal projection to the torus semicircularis as well as projections to the retina from three different sources in the brain are described. After intra-ocular injections of HRP, labeled cells were found in the optic tectum, the dorsomedial optic nucleus and one of the pretectal nuclei. These new findings support the basic hypothesis (i) that neuronal connections are more extensive in primitive brains, and (ii) that the evolutionary development of more complex brains involves the loss of some selected connections.


A Bayesian spatio-temporal analysis of mortality rates in Spain: application to the COVID-19 2020 outbreak.
The number of deaths attributable to COVID-19 in Spain has been highly controversial since it is problematic to tell apart deaths having COVID as the main cause from those provoked by the aggravation by the viral infection of other underlying health problems. In addition, overburdening of health system led to an increase in mortality due to the scarcity of adequate medical care, at the same time confinement measures could have contributed to the decrease in mortality from certain causes. Our aim is to compare the number of deaths observed in 2020 with the projection for the same period obtained from a sequence of previous years. Thus, this computed mortality excess could be considered as the real impact of the COVID-19 on the mortality rates. The population was split into four age groups, namely: (< 50; 50-64; 65-74; 75 and over). For each one, a projection of the death numbers for the year 2020, based on the interval 2008-2020, was estimated using a Bayesian spatio-temporal model. In each one, spatial, sex, and year effects were included. In addition, a specific effect of the year 2020 was added ("outbreak"). Finally, the excess deaths in year 2020 were estimated as the count of observed deaths minus those projected. The projected death number for 2020 was 426,970 people, the actual count being 499,104; thus, the total excess of deaths was 72,134. However, this increase was very unequally distributed over the Spanish regions. Bayesian spatio-temporal models have proved to be a useful tool for estimating the impact of COVID-19 on mortality in Spain in 2020, making it possible to assess how the disease has affected different age groups accounting for effects of sex, spatial variation between regions and time trend over the last few years.


Saikosaponins induced hepatotoxicity in mice via lipid metabolism dysregulation and oxidative stress: a proteomic study.
Radix Bupleuri (RB) has been popularly used for treating many liver diseases such as chronic hepatic inflammation and viral Hepatitis in China. Increasing clinical and experimental evidence indicates the potential hepatotoxicity of RB or prescriptions containing RB. Recently, Saikosaponins (SS) have been identified as major bioactive compounds isolated from RB, which may be also responsible for RB-induced liver injury. Serum AST, ALT and LDH levels were determined to evaluate SS-induced liver injury in mice. Serum and liver total triglyceride and cholesterol were used to indicate lipid metabolism homeostasis. Liver ROS, GSH, MDA and iNOS were used to examine the oxidative stress level after SS administration. Western blot was used to detect CYP2E1 expression. A 8-Plex iTRAQ Labeling Coupled with 2D LC - MS/MS technique was applied to analyze the protein expression profiles in livers of mice administered with different doses of SS for different time periods. Gene ontology analysis, cluster and enrichment analysis were employed to elucidate potential mechanism involved. HepG2 cells were used to identify our findings in vitro. SS dose- and time-dependently induced liver injury in mice, indicated by increased serum AST, ALT and LDH levels. According to proteomic analysis, 487 differentially expressed proteins were identified in mice administrated with different dose of SS for different time periods. Altered proteins were enriched in pathways such as lipid metabolism, protein metabolism, macro molecular transportation, cytoskeleton structure and response to stress. SS enhanced CYP2E1 expression in a time and dose dependent manner, and induced oxidative stress both in vivo and in vitro. Our results identified hepatotoxicity and established dose-time course-liver toxicity relationship in mice model of SS administration and suggested potential mechanisms, including impaired lipid and protein metabolism and oxidative stress. The current study provides experimental evidence for clinical safe use of RB, and also new insights into understanding the mechanism by which SS and RB induced liver injury.


Neo-vascularization-based therapeutic perspectives in advanced ovarian cancer.
The process of angiogenesis is well described for its potential role in the development of normal ovaries, and physiological functions as well as in the initiation, progression, and metastasis of ovarian cancer (OC). In advanced stages of OC, cancer cells spread outside the ovary to the pelvic, abdomen, lung, or multiple secondary sites. This seriously limits the efficacy of therapeutic options contributing to fatal clinical outcomes. Notably, a variety of angiogenic effectors are produced by the tumor cells to initiate angiogenic processes leading to the development of new blood vessels, which provide essential resources for tumor survival, dissemination, and dormant micro-metastasis of tumor cells. Multiple proangiogenic effectors and their signaling axis have been discovered and functionally characterized for potential clinical utility in OC. In this review, we have provided the current updates on classical and emerging proangiogenic effectors, their signaling axis, and the immune microenvironment contributing to the pathogenesis of OC. Moreover, we have comprehensively reviewed and discussed the significance of the preclinical strategies, drug repurposing, and clinical trials targeting the angiogenic processes that hold promising perspectives for the better management of patients with OC.


Chronic occupational exposure to toluene.
Chronic occupational exposure to toluene was studied in a factory preparing tarpaulins. Seventy-eight workers were studied; 46 were exposed to various concentrations of toluene in air (20--200 ppm), 32 were unexposed workers in the same factory. In many cases the exposure had lasted for 10--20 years. The urinary hippuric acid excretion at the end of work shift showed good correlations to toluene concentrations in air, and it seems to be a good measure of exposure. The hippuric acid in urine samples collected overnight showed that elimination of toluene still occurs several hours after exposure. Most of the biological parameters measured showed no correlation to toluene exposure. The blood leukocyte count did not show slight positive correlations to toluene exposure, but even this parameter stayed inside the range of normal values. The occurrence of chronic diseases, drug using habits, and drinking and smoking habits did not show any correlations to toluene exposure.


Fused filament fabrication (FFF): influence of layer height on forces and moments delivered by aligners-an in vitro study.
To investigate the effect of layer height of FFF-printed models on aligner force transmission to a second maxillary premolar during buccal torquing, distalization, extrusion, and rotation using differing foil thicknesses. Utilizing OnyxCeph3™ Lab (Image Instruments GmbH, Chemnitz, Germany, Release Version 3.2.185), the following movements were programmed for the second premolar: buccal torque (0.1-0.5 mm), distalization (0.1-0.4 mm), extrusion (0.1-0.4 mm), rotation (0.1-0.5 mm), and staging 0.1 mm. Via FFF, 91 maxillary models were printed for each staging at different layer heights (100 µm, 150 µm, 200 µm, 250 µm, 300 µm). Hence, 182 aligners, made of polyethylene terephthalate glycol (PET-G) with two thicknesses (0.5 mm and 0.75 mm), were prepared. The test setup comprised an acrylic maxillary model with the second premolar separated and mounted on a sensor, measuring initial forces and moments exerted by the aligners. A generalized linear model for the gamma distribution was applied, evaluating the significance of the factors layer height, type of movement, aligner thickness, and staging on aligner force transmission. Foil thickness and staging were found to have a significant influence on forces delivered by aligners, whereas no significance was determined for layer height and type of movement. Nevertheless, at a layer height of 150 µm, the most appropriate force transmission was observed. Printing aligner models at particularly low layer heights leads to uneconomically high print time without perceptible better force delivery properties, whereas higher layer heights provoke higher unpredictability of forces due to scattering. A z-resolution of 150 µm appears ideal for in-office aligner production combining advantages of economic print time and optimal force transmission.


One-pot synthesis of dual carbon dots using only an N and S co-existed dopant for fluorescence detection of Ag.
Luminescent carbon-based nanoparticles, named often as carbon dots (CDs), were synthesized from citric acid (CA) and guanidine thiocyanate (GITC) via an N and S co-doped hydrothermal procedure. In the present structure characterization, N and S elements could be sufficiently doped by means of the heteroatom or the functional groups bonded on the surface of CDs. The as-prepared CDs solution showed blue color fluorescence under ultraviolet excitation, yet the PL spectra exhibited a repetitive emission process from excitation-independent to excitation-dependent. In view of the triexponential feature of fluorescence lifetimes of CDs, one possibility was proposed to be co-existence of two types of CDs with different surface states. Additionally, the as-prepared CDs were used as a sensing probe for the detection of Ag+ taking into consideration of the possible interactions between Ag+ and various fluorophores attached to the CD surface. As expected, the changes of fluorescence intensities were linearly proportional to the different concentration ranges of Ag+, which suggests the complex nature of the quenching mechanism. And for the first time, the SCN group was found to accelerate the quenching of CDs towards Ag+, promising a new approach for efficient detection of Ag+ for the application in industrial pollutants.


Sphingolipids in pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by alveolar epithelial cell injury, accumulation of fibroblasts/myofibroblasts and deposition of extracellular matrix proteins. Levels of sphingosine-1-phosphate (S1P), a naturally occurring bioactive lipid, are elevated in bronchoalveolar fluids and lung tissues from IPF patients and animal models of pulmonary fibrosis. However, the in vivo contribution of S1P, regulated by its synthesis catalyzed by Sphingosine kinases (SphKs) 1 & 2 and catabolism by S1P phosphatases and S1P lyase (S1PL), in the pathogenesis of pulmonary fibrosis is not well defined. Microarray analysis of blood mononuclear cells from patients with IPF and SphK1-, SphK2- or S1PL-knockout mice and SphK inhibitor were used to assess the role of S1P in fibrogenesis. The expression of SphK1 negatively correlated with lung function and survival of patients with IPF. Further, the expressions of SphK1 and S1PL were increased in lung tissues from patients with IPF and bleomycin-challenged mice. Genetic knockdown of SphK1, but not SphK2, ameliorated bleomycin-induced pulmonary fibrosis in mice while deletion of S1PL (SGPL1(+/-)) in mice potentiated fibrosis post-bleomycin challenge. TGF-β increased the expression of SphK1 and S1PL in human lung fibroblasts and knockdown of SphK1 or treatment with SphK inhibitor attenuated S1P generation and TGF-β mediated signal transduction. Over-expression of S1PL attenuated bleomycin-induced TGF-β secretion and S1P mediated differentiation of human lung fibroblasts through regulation of autophagy. Administration of SphK1 inhibitor 8 days post-bleomycin challenge reduced bleomycin-induced mortality and pulmonary fibrosis. Our results suggest that SphK1 and S1PL play critical roles in the pathology of lung fibrosis and may be novel therapeutic targets.


Age-related changes in B and T lymphocytes and decline of humoral immune responsiveness in aged mice.
The activity of the immune system declines in an age-related fashion, after reaching a peak in young-adult animals. Although this pattern has been well documented, the mechanisms responsible for the decline of immune potential in senescence have not been fully elucidated. At the same time, it has become apparent that the immune response depends on complex interactions among different cell types. We review the results of the analyses of B- and T-lymphocyte function and activity in the humoral responsiveness of aged mice that have been performed in a number of laboratories, with a variety of experimental techniques. We conclude that an increase in T-cell suppressor function is the first immunologic lesion of aging in mice. This is followed by a decrease in T-cell helper function and finally by a loss of B-cell function.


Chemical cross-linking and protein-protein interactions-a review with illustrative protocols.
The general term "protein-protein" interactions refers to the effects of proteins upon each other. The interactions can arise from co-existence in organized structural arrangements or in transient encounters. The latter are difficult to detect and define. Introduction of specific, stable chemical linkages can establish permanent relationships between what would normally be transiently associated species. The review covers the types and purposes of various linkers, including the comparative advantages of various approaches. The emphasis is on practical applications and thus includes methodology in the form of practical protocols for introducing the linkages and interpreting the outcomes.


Evaluation of Domestication Loci Associated with Awnlessness in Cultivated Rice, Oryza sativa.
Awns are bristle-like organs at the tips of the glumes. Wild rice has maintained long awns for successful seed propagation through seed dispersal. Seed awning is an interesting trait in rice domestication. Long awns might have been beneficial for seed gatherers in the initial phase of domestication; however, awnless phenotypes were preferably selected in a later phase with non-seed-shattering plants. Investigation of domestication loci associated with awnlessness in cultivated rice will be useful in clarifying the process and history of rice domestication. Quantitative trait locus (QTL) analysis for seed awning was carried out using a BC3F2 population between Oryza sativa IR36 (a cultivated donor parent with awnless phenotype) and O. rufipogon W630 (a wild recurrent parent with awns). As a result, two QTLs on chromosome 4 (corresponding to An-1 and LABA1) and one on chromosome 2 (designated as qAWNL2) were detected. Gene interaction among three seed-awning QTLs were further examined with the plants having eight different combinations of homozygous genotypes. Their awn length variation indicated that the IR36 alleles at these loci had the additive awnlessness effects in the genetic background of wild rice. The shortest awn length was observed for the plants having IR36 homozygous alleles at all loci, giving about 75% reduction in awn length. By the fine mapping, the candidate region of the novel qAWNL2 locus was delimited in a 157.4-kb region containing 22 predicted genes in Nipponbare genome. QTL analysis revealed that three loci, An-1, LABA1 and qAWNL2, were mainly responsible for the awnlessness of O. sativa IR36. In the wild genetic background, loss-of-function alleles at three awning loci showed additive effects on length reduction. In rice domestication, awnless forms may be gradually generated through the accumulation of mutations at awning loci.


Highly Similar Sequence and Structure Yet Different Biophysical Behavior: A Computational Study of Two Triosephosphate Isomerases.
Homodimeric triosephosphate isomerases (TIMs) from Trypanosoma cruzi (TcTIM) and Trypanosoma brucei (TbTIM) have markedly similar amino-acid sequences and three-dimensional structures. However, several of their biophysical parameters, such as their susceptibility to sulfhydryl agents and their reactivation speed after being denatured, have significant differences. The causes of these differences were explored with microsecond-scale molecular dynamics (MD) simulations of three different TIM proteins: TcTIM, TbTIM, and a chimeric protein, Mut1. We examined their electrostatic interactions and explored the impact of simulation length on them. The same salt bridge between catalytic residues Lys 14 and Glu 98 was observed in all three proteins, but key differences were found in other interactions that the catalytic amino acids form. In particular, a cation-π interaction between catalytic amino acids Lys 14 and His 96 and both a salt bridge and a hydrogen bond between catalytic Glu 168 and residue Arg 100 were only observed in TcTIM. Furthermore, although TcTIM forms less hydrogen bonds than TbTIM and Mut1, its hydrogen bond network spans almost the entire protein, connecting the residues in both monomers. This work provides new insight into the mechanisms that give rise to the different behavior of these proteins. The results also show the importance of long simulations.