Structural Changes in N-Glycans on Induced Pluripotent Stem Cells Differentiating Toward Cardiomyocytes.
Cell-surface glycans vary widely, depending on cell properties. Previously, we reported that the pattern of N-glycan expression on murine induced pluripotent stem cells (iPSCs) changed toward that of the cardiac tissue during cardiomyogenic differentiation. In this study, N-glycans were isolated from human iPSCs, iPSC-derived cardiomyocytes (iPSC-CMs), and human cardiomyocytes (hCMCs). Their structures were analyzed by a mapping technique based on high-performance liquid chromatography elution positions and matrix-assisted laser desorption/ionization time-of-flight mass-spectrometric data. Of 52 isolated N-glycans, the structures of 38 were clearly identified. In addition, 11 structures were partially identified because the binding style and fucose binding site at the nonreduced terminal could not be identified. Quantitation of each type of N-glycan, based on the terminal glycosylation process, revealed that the exposed N-acetylglucosamine (GlcNAc) and the nonreduced terminal fucose types decreased, whereas the exposed galactose or the α2-3 NeuAc types increased in the iPSCs during cardiomyogenic differentiation. However, the bisecting GlcNAc and the triantennary structures were found in relative abundance in the iPSC-CMs in comparison with hCMCs or iPSCs. Expression of MGAT3, a glycosyltransferase-encoding gene that produces the bisecting GlcNAc structures, was higher in iPSCs and iPSC-CMs than in hCMCs. These findings will prove useful in understanding the directional precision of cardiomyogenic differentiation in vitro. This study focused on N-glycans produced in human induced pluripotent stem cells (iPSCs) and iPSC-derived cardiomyocytes to investigate their change on cardiomyogenic differentiation in vitro. This shows that the expression pattern of N-glycans in human iPSCs changed toward the pattern observed in human cardiomyocytes upon cardiomyogenic differentiation. Structural differences were also observed in the bisecting N-acetylglucosamine and the triantennary structures upon cardiomyogenic differentiation. The findings of this study will help in understanding the directional precision of cardiomyogenic differentiation in vitro.


Concentration and composition of human serum lipoproteins at birth.
By ultracentrifugation of sera from 69 cord bloods very low (VLDL), low (LDL) and high density lipoproteins (HDL) were obtained and analysed for triglycerides (TG) and cholesterol (CHOL). Electrophoresis in agarose gel was performed on serum, VLDL and LDL + HDL. VLDL lipids were present in all newborns. VLDL contained 30 and 5% of serum TG and CHOL. The range of TG in VLDL was wide (0.02-0.62 mmol/l), but there was a constant ratio between TG and CHOL. The electrophoretic mobility of VLDL was slower than in adults. LDL contained 50% of both serum TG and CHOL, and HDL contained 15 and 50% of these serum lipids. A published formula for calculating CHOL in VLDL and LDL from serum CHOL and TG and CHOL in HDL gave values for CHOL in LDL which corresponded well with the determined values. For VLDL, however, the calculated values were too high.


Draft Genome Sequences of Lactococcus lactis Strains MS22314, MS22333, MS22336, and MS22337, Isolated from Fermented Camel Milk in Ethiopia.
The genome sequences of four Lactococcus lactis strains isolated from fermented camel milk were sequenced using paired-end Illumina MiSeq reads. The genome size of each strain was about 2.6 Mb, and three of the strains were annotated with tet(S) coding for tetracycline resistance.


Factors associated with intensive care unit delirium in patients with acute myocardial infarction.
Some patients admitted to intensive care units (ICU) would develop delirium, which is associated with poor prognosis. The purpose of this retrospective study was to identify factors associated with ICU delirium in patients with acute myocardial infarction (AMI). We included 753 AMI and divided those into the ICU-delirium group (n = 110) and the non-ICU-delirium group (n = 643) according to the presence of ICU delirium. The ICU delirium was evaluated by confusion assessment method for the intensive care unit. Patient characteristics and clinical outcomes were compared between the 2 groups, and factors associated with ICU delirium were sought by multivariate analysis. The prevalence of female sex was significantly higher in the ICU-delirium group (43.6%) than in the non-ICU-delirium group (20.2%) (p < 0.001). The incidence of in-hospital death was significantly higher in the ICU-delirium group (17.3%) than in the non-ICU-delirium group (0.5%) (p < 0.001). The multivariate logistic regression analysis revealed that age [every 10 years increase: odds ratio (OR) 1.439, 95% confidence interval (CI) 1.127-1.837, p = 0.004], female sex (OR 2.237, 95%CI 1.300-3.849, p = 0.004), triple vessel disease (OR 2.317, 95%CI 1.365-3.932, p = 0.002), body mass index < 18.5 kg/m2 (OR 2.910, 95%CI 1.410-6.008, p = 0.004), use of mechanical support (OR 2.812, 95%CI 1.500-5.270, p = 0.001), respiratory failure (OR 5.342, 95%CI 3.080-9.265, p < 0.001), and use of continuous renal replacement therapy (OR 5.901, 95%CI 2.520-13.819, p < 0.001) were significantly associated with ICU delirium. In conclusion, ICU delirium was associated with in-hospital death. Older age, female sex, triple vessel disease, leanness, use of mechanical support, respiratory failure, and continuous renal replacement therapy were significantly associated with the occurrence of ICU delirium.


Comparison of aflatoxin B1 and aflatoxin G1 binding to cellular macromolecules in vitro, in vivo and after peracid oxidation; characterisation of the major nucleic acid adducts.
A comparison between [14C]aflatoxin B1 (AFB1) and [14C]aflatoxin G1 (AFG1) binding to rat liver and kidney cellular macromolecules has shown AFG1-DNA and-ribosomal RNA binding to be lower in both organs. For both mycotoxins more was bound to nucleic acids than to protein. Two hours after intraperitoneal injection (60 microgram/100 g) of [14C] AFB1, 40 ng, 151 ng/mg. Loss of radioactivity bound to liver DNA for both [14C]AFB1 and protein respectively and for [14C]AFG1 the respective figures were 10, 7 and 1 ng/mg. Loss of liver bound radioactivity to DNA for both [14C]AFG1 and [14C]AFG1 appeared to be biphasic indicating that an enzymic DNA repair process may be operating. In vitro binding studies also showed less AFG1 was bound to exogenous DNA after microsomal activation than AFB1. This difference was not a result of differences in the chemical reactivity of the "ultimate" electrophilic species, the respective expoxides, since chemical activation studies using 3-chloroperbenzoic acid showed similar amounts of AFG1 and AFB1 to be converted to the epoxides and to bind to DNA. Studies on the distribution coefficients of the two mycotoxins showed AFB1 to be more lipophilic than AFG1 and this may be an important factor in determining the weaker carcinogenicity of the latter compound. Characterisation of the major AFG1-DNA adduct formed in vitro, in vivo and after peracid oxidation showed it to have the structure trans-9,10-dihydro-9-(7-guanyl)-10-hydroxy-aflatoxin G1. This adduct is similar to that obtained from AFB1 by activation in vivo, in vitro and after peracid oxidation.


[Disabled elderly people waiting for institutionalization to a hospital ward: prospective study in the administrative district of Strasbourg (France)].
Our aim was to estimate the number of non-satisfied instutionalization requests for inpatients and to describe the strategies elaborated to compensate for the waiting time. This prospective follow-up study concerning all requests for institution admission for inpatients aged 75 years or older hospitalized in acute care and rehabilitation wards. Descriptive data were gathered throughout the social support process conducted during the hospitalization. A three months follow-up was conducted. Among 5200 hospitalizations, a social support process was initiated for 270 patients aged 75 years and over. Two thirds of the sample were women (n=163). Mean age was 82 years. Fifty-two percent of the subjects met the criteria for iso-resource grades (IRG) 1 to 2 and 90% in IRG 1 to 4. The mean length of hospitalized stay (MLOS) was 56.8+/-10.2 days; the MLOS of unjustified stay of 23.5+/-5.6 (n=222). The average time before the social worker was informed of the patient's situation was 13.6+/-2.0 days; in addition, the time required to establish the administrative documents necessary for initiation of the social support progress was 15.0+/-1.8. The principal reasons for social support were physical dependence (77%), mental dependence (60%), insufficient family support (36%) and/or disease progression (21%). At three months, 104 patients were institutionalized, 128 were still on institution waiting list (in hospital: 48%; at home: 16%) and 38 had died (14%). The estimated annual institutional deficit for disabled elderly people was 512 beds. In light of demographical perspectives, an overall re-organization of the geriatric network is absolutely necessary. A simple increase in the capacity to fulfil the institutional beds deficit would be insufficient.


Arsenite and arsenate removal from wastewater using cationic polymer-modified waste tyre rubber.
Waste tyre rubber (WTR) granulate was modified with a cationic polymer, poly(3-acrylamidopropyl)trimethylammonium chloride (p(APTMACl)). The resulting WTR/p(APTMACl) was utilized for the adsorption of arsenite, As(III) and arsenate, As(V) from aqueous medium in both batch and column methods. The level of adsorption increased gradually with increasing monomer concentration and contact time. The adsorption behavior obeyed the Freundlich model, and the rate of adsorption could be predicted by employing the pseudo-second order model. In the column method, As(V) could be adsorbed onto the sorbent more effectively than As(III). Remarkable desorption of As(III) and As(V) (99 and 92%, respectively) from the adsorbent was achieved using 0.10 M HCl as eluent. An approach of evaluation of adsorption capacity uncertainty is proposed.


Quantitative bias analysis in practice: review of software for regression with unmeasured confounding.
Failure to appropriately account for unmeasured confounding may lead to erroneous conclusions. Quantitative bias analysis (QBA) can be used to quantify the potential impact of unmeasured confounding or how much unmeasured confounding would be needed to change a study's conclusions. Currently, QBA methods are not routinely implemented, partly due to a lack of knowledge about accessible software. Also, comparisons of QBA methods have focused on analyses with a binary outcome. We conducted a systematic review of the latest developments in QBA software published between 2011 and 2021. Our inclusion criteria were software that did not require adaption (i.e., code changes) before application, was still available in 2022, and accompanied by documentation. Key properties of each software tool were identified. We provide a detailed description of programs applicable for a linear regression analysis, illustrate their application using two data examples and provide code to assist researchers in future use of these programs. Our review identified 21 programs with [Formula: see text] created post 2016. All are implementations of a deterministic QBA with [Formula: see text] available in the free software R. There are programs applicable when the analysis of interest is a regression of binary, continuous or survival outcomes, and for matched and mediation analyses. We identified five programs implementing differing QBAs for a continuous outcome: treatSens, causalsens, sensemakr, EValue, and konfound. When applied to one of our illustrative examples, causalsens incorrectly indicated sensitivity to unmeasured confounding whereas the other four programs indicated robustness. sensemakr performs the most detailed QBA and includes a benchmarking feature for multiple unmeasured confounders. Software is now available to implement a QBA for a range of different analyses. However, the diversity of methods, even for the same analysis of interest, presents challenges to their widespread uptake. Provision of detailed QBA guidelines would be highly beneficial.


Biochemical analysis of Escherichia coli selenophosphate synthetase mutants. Lysine 20 is essential for catalytic activity and cysteine 17/19 for 8-azido-ATP derivatization.
A labile selenium donor compound, selenophosphate, is formed from selenide and ATP by selenophosphate synthetase. A cysteine residue (Cys-17) that is essential for catalytic activity of the enzyme (Kim, I.Y., Veres, Z., and Stadtman, T. C. (1992) J. Biol. Chem. 267, 19650-19654) is located in a glycine-rich segment near the N terminus of the protein. The possibility that this peptide sequence (HGAGCGCK) defines the ATP-binding site of the enzyme, as does a conserved ATP or GTP binding sequence (GXXXXGKS/T) found in several other proteins, was tested by site-specific mutagenesis. Thus His-13 and Gly-18 were changed to Asn and Val, respectively, and Lys-20 to Arg or Gln. Catalytic activity was markedly decreased by mutation of Lys-20 to Arg and abolished by mutation of Lys-20 to Gln. The mutation of Cys-19 and His-13 did not substantially alter the ATP Km and Vmax values, whereas the Gly-18 mutation resulted in a 4-fold increase in the ATP Km value compared with that of the wild type. ATP binding properties of the mutant enzymes were determined using Mn-[32P]ATP or Mn-[14C]ATP and gel filtration. Photoaffinity labeling of the proteins with [gamma-32P]8-azido-ATP showed that all mutant enzymes could be labeled with the ATP analog except those in which Cys-17 or Cys-19 were replaced with serine.


Comparison of short- and long-term outcomes after early versus late liver retransplantation: a single-center experience.
As the survival of patients after liver transplantation (LT) improves, the requirement of liver retransplantation (reLT) for late graft failure has grown. Although some have reported that the short-term outcome of late reLT was comparable with that of early reLT, it remains unknown whether long-term survival of late reLT is inferior to that of early reLT patients. We reviewed early (<6 mo after primary LT) and late (≥6 mo after primary LT) reLT cases performed between January 2000 and December 2010. Sixteen early and 32 late reLT cases were analyzed. There was no significant difference regarding the number of units of red blood cells transfused during the transplantation between the groups, whereas operative time was significantly longer in the late reLT cases. Graft loss within 3 mo after early and late reLT was 18.6% and 15.6%, respectively. Patient and graft survival rates after 1, 3, 5, and 10 y in the late reLT group were 80.6%, 73.3%, 73.3%, and 67.7% and 80.7%, 69.1%, 63.3%, and 54.3%, respectively, whereas those in the early reLT group were 75.0%, 75.0%, 64.3%, and 64.3% and 81.3%, 75.0%, 64.3%, and 32.1%, respectively. There was no significant difference in patient or graft survival rates between the groups (P = 0.91 and 0.91, respectively). Acceptable short- and long-term survival were provided in early and late reLT. The time between the primary LT and reLT does not seem to play significant role in the prognosis of reLT in the long term.


Cell cycle control in the terminally differentiated myocyte. A platform for myocardial repair?
Currently available pharmaceuticals exert beneficial effects on morbidity and mortality in heart failure. Only cardiac transplantation, however, provides a definitive solution to the irreversible loss of cardiomyocytes in the failing heart. The limited availability of donor hearts leaves the vast majority of afflicted patients in need. The need for innovative approaches to improve care for these patients is apparent.


Free-breathing myocardial T1 mapping using inversion-recovery radial FLASH and motion-resolved model-based reconstruction.
To develop a free-breathing myocardial T 1 $$ {\mathrm{T}}_1 $$ mapping technique using inversion-recovery (IR) radial fast low-angle shot (FLASH) and calibrationless motion-resolved model-based reconstruction. Free-running (free-breathing, retrospective cardiac gating) IR radial FLASH is used for data acquisition at 3T. First, to reduce the waiting time between inversions, an analytical formula is derived that takes the incomplete T 1 $$ {\mathrm{T}}_1 $$ recovery into account for an accurate T 1 $$ {\mathrm{T}}_1 $$ calculation. Second, the respiratory motion signal is estimated from the k-space center of the contrast varying acquisition using an adapted singular spectrum analysis (SSA-FARY) technique. Third, a motion-resolved model-based reconstruction is used to estimate both parameter and coil sensitivity maps directly from the sorted k-space data. Thus, spatiotemporal total variation, in addition to the spatial sparsity constraints, can be directly applied to the parameter maps. Validations are performed on an experimental phantom, 11 human subjects, and a young landrace pig with myocardial infarction. In comparison to an IR spin-echo reference, phantom results confirm good T 1 $$ {\mathrm{T}}_1 $$ accuracy, when reducing the waiting time from 5 s to 1 s using the new correction. The motion-resolved model-based reconstruction further improves T 1 $$ {\mathrm{T}}_1 $$ precision compared to the spatial regularization-only reconstruction. Aside from showing that a reliable respiratory motion signal can be estimated using modified SSA-FARY, in vivo studies demonstrate that dynamic myocardial T 1 $$ {\mathrm{T}}_1 $$ maps can be obtained within 2 min with good precision and repeatability. Motion-resolved myocardial T 1 $$ {\mathrm{T}}_1 $$ mapping during free-breathing with good accuracy, precision and repeatability can be achieved by combining inversion-recovery radial FLASH, self-gating and a calibrationless motion-resolved model-based reconstruction.


Outcomes in elderly patients undergoing hepatic resection compared to liver transplant for hepatocellular carcinoma.
Hepatic resection (HR) is an excellent option for patients with hepatocellular carcinoma (HCC). For patients meeting the Milan criteria, a liver transplant (LT) is also a viable option for patients with HCC, especially those with end-stage liver disease. With increasing rates of LTs amongst the elderly, we sought to determine long-term outcomes in patients who underwent HR compared to LTs in this patient population. We queried the national cancer database for elderly patients (≥70 years) diagnosed with HCC between 2004 and 2020. The primary outcome was overall survival (OS) computed using the Kaplan-Meier method and Cox proportional hazard regression. One-to-one propensity score matching was conducted on the basis of clinicodemographic features to account for baseline differences between patients undergoing each procedure. Of the 5090 patients included, 4674 (91.8%) and 416 (8.2%) patients underwent HR and LT, respectively. Compared with HR patients, patients receiving LT had better OS (p < 0.001) and greater median survival time (65.6 months HR vs. 97.9 months LT, p < 0.001). On multivariable analysis, a LT was independently associated with improved survival (adjusted hazard ratio: 0.61, 95% confidence interval: 0.50-0.76, p < 0.001). LT is associated with improved survival for well-selected elderly patients with HCC. Age alone should not be used as the sole parameter for the candidacy of LT in elderly patients.


Transcriptional Activation of the Zygotic Genome in Drosophila.
During the first stages of metazoan development, the genomes of the highly specified sperm and egg must unite and be reprogrammed to allow for the generation of a new organism. This process is controlled by maternally deposited products. Initially, the zygotic genome is largely transcriptionally quiescent, and it is not until hours later that the zygotic genome takes control of development. The transcriptional activation of the zygotic genome is tightly coordinated with the degradation of the maternal products. Here, we review the current understanding of the processes that mediate the reprogramming of the early embryonic genome and facilitate transcriptional activation during the early stages of Drosophila development.


Comparative Assessment of Different Ultrasound Technologies in the Detection of Prostate Cancer: A Systematic Review and Meta-Analysis.
The present study aimed to assess the diagnostic test accuracy of different ultrasound scanning technologies in the detection of prostate cancer. A systematic search was conducted using the Cochrane Guidelines for Screening and Diagnostic Tests. We performed a systematic search in the international databases PubMed, Medline, Ovid, Embase and Cochrane Library. Searches were designed to find all studies that evaluated Micro-US, mpUS, SWE and CEUS as the main detection modalities for prostate cancer. This study was registered with Research Registry of systematic review and meta-analysis. The QUADAS-2 tool was utilized to perform quality assessment and bias analysis. The literature search generated 1376 studies. Of these, 320 studies were screened for eligibility, with 1056 studies being excluded. Overall, 26 studies with a total of 6370 patients met the inclusion criteria. The pooled sensitivity for grayscale, CEUS, SWE, Micro-US and mpUS modalities were 0.66 (95% CI 0.54-0.73) 0.73 (95% CI 0.58-0.88), 0.82 (95% CI 0.75-0.90), 0.85 (95% CI 0.76-0.94) and 0.87 (95% CI 0.71-1.03), respectively. Moreover, the pooled specificity for grayscale, CEUS, SWE, Micro-US and mpUS modalities were 0.56 (95% CI 0.21-0.90), 0.78 (95% CI 0.67-0.88), 0.76 (95% CI 0.65-0.88), 0.43 (95% CI 0.28-0.59) and 0.68 (95% CI 0.54-0.81), respectively. In terms of sensitivity, substantial heterogeneity between studies was detected (I2 = 72%, p = 0.000 < 0.05). In relation to specificity, extreme heterogeneity was detected (I2 = 93%, p = 0.000 < 0.05). Some studies proved that advanced ultrasound modalities such as mpUS, Micro-US, shear-wave elastography, contrast enhanced and micro-ultrasound are promising methods for the detection of prostate cancer.


Selection of the type of urinary diversion in conjunction with radical cystectomy.
Several different methods of urinary diversion currently are available for use in conjunction with radical cystectomy. The method of urinary diversion performed at the time of radical cystectomy was reviewed for patients undergoing surgery from April 1984 through March 1986. A total of 91 urinary diversions was performed. Of the patients 74 per cent had a diversion with an external appliance (including 68 per cent with an ileal conduit), 14 per cent had a continent urinary reservoir (Kock pouch) and 11 per cent had an internal reservoir anastomosed to the urethra and, thus, avoided any stoma. There are inherent disadvantages to each form of urinary diversion and patient selection will be important to identify the most appropriate method of diversion for an individual.


Systematical identification of splicing regulatory cis-elements and cognate trans-factors.
The majority of human genes undergo alternative splicing to generate multiple isoforms with distinct functions. This process is generally controlled by cis-acting splicing regulatory elements (SREs) that recruit trans-acting factors to promote or inhibit the use of nearby splice sites. The growing interest in understanding the regulatory rules of splicing necessitates the systematic identification of these SREs and their cognate protein factors using experimental and computational approaches. Here we describe a strategy to identify and analyze both cis-acting SREs and trans-acting splicing factors. This strategy involves a cell-based screen to identify SREs from a random sequences library and a modified RNA affinity purification approach to unbiasedly identify the splicing factors. These methods can be adopted to identify splicing enhancers or silencers in both exons and introns, and can be extended to different cultured cells. The resulting SREs and splicing factors can be further analyzed with a series of computational and experimental approaches. This approach will help us to collect a molecular part-list for splicing regulation, providing a rich data source that enables a better understanding of the "splicing code".


Chicken liver amidophosphoribosyltransferase. Ligand-induced alterations in molecular properties.
A homogeneous amidophosphoribosyltransferase (EC 22.214.171.124) preparation, which was sensitive to purine nucleotide inhibitors, was obtained from chicken liver. From the result of sodium dodecyl sulfate polyacrylamide gel electrophoresis, the subunit weight was estimated to be approximately 58 000. In Tris-HCl buffer, the predominant form of the enzyme had an S20,w of 6.5, Strokes radius of 40 A, and estimated molecular weight of 110 000. Incubation with 5-phosphoribosyl 1-pyrophosphate or Pi resulted in an increase in the S20,w to 9.1--9.5, Strokes radius 50 A, and estimated molecular weight to 200 000. Incubation of the large form with AMP led to a decrease in the molecular wight of the enzyme. It is concluded that chicken liver amidophosphoribosyltransferase is an allosteric protein whose activity is regulated by a series of conformational changes induced by a number of ligands.


Hypothermia therapy for newborns with hypoxic ischemic encephalopathy.
Therapeutic hypothermia reduces cerebral injury and improves the neurological outcome secondary to hypoxic ischemic encephalopathy in newborns. It has been indicated for asphyxiated full-term or near-term newborn infants with clinical signs of hypoxic-ischemic encephalopathy (HIE). A search was performed for articles on therapeutic hypothermia in newborns with perinatal asphyxia in PubMed; the authors chose those considered most significant. There are two therapeutic hypothermia methods: selective head cooling and total body cooling. The target body temperature is 34.5 °C for selective head cooling and 33.5 °C for total body cooling. Temperatures lower than 32 °C are less neuroprotective, and temperatures below 30 °C are very dangerous, with severe complications. Therapeutic hypothermia must start within the first 6h after birth, as studies have shown that this represents the therapeutic window for the hypoxic-ischemic event. Therapy must be maintained for 72 h, with very strict control of the newborn's body temperature. It has been shown that therapeutic hypothermia is effective in reducing neurologic impairment, especially in full-term or near-term newborns with moderate hypoxic-ischemic encephalopathy. Therapeutic hypothermia is a neuroprotective technique indicated for newborn infants with perinatal asphyxia and hypoxic-ischemic encephalopathy.


Prevalence of genotoxic chemicals among animal and human carcinogens evaluated in the IARC Monograph Series.
To determine whether genotoxic and non-genotoxic carcinogens contribute similarly to the cancer burden in humans, an analysis was performed on agents that were evaluated in Supplements 6 and 7 to the IARC Monographs for their carcinogenic effects in humans and animals and for the activity in short-term genotoxicity tests. The prevalence of genotoxic carcinogens on four groups of agents, consisting of established human carcinogens (group 1, n = 30), probable human carcinogens (group 2A, n = 37), possible human carcinogens (group 2B, n = 113) and on agents with limited evidence of carcinogenicity in animals (a subset of group 3, n = 149) was determined. A high prevalence in the order of 80 to 90% of genotoxic carcinogens was found in each of the groups 1, 2A and 2B, which were also shown to be multi-species/multi-tissues carcinogens. The distribution of carcinogenic potency in rodents did not reveal any specific characteristic of the human carcinogens in group 1 that would differentiate them from agents in groups 2A, 2B and 3. The results of this analysis indicate that (a) an agent with unknown carcinogenic potential showing sufficient evidence of activity in in vitro/in vivo genotoxicity assays (involving as endpoints DNA damage and chromosomal/mutational damage) may represent a hazard to humans; and b) an agent showing lack of activity in this spectrum of genotoxicity assays should undergo evaluation for carcinogenicity by rodent bioassay, in view of the present lack of validated short-term tests for non-genotoxic carcinogens. Overall, this analysis implies that genotoxic carcinogens add more to the cancer burden in man than non-genotoxic carcinogens. Thus, identification of such genotoxic carcinogens and subsequent lowering of exposure will remain the main goal for primary cancer prevention in man.


The Preoperative Evaluation of Drug-Resistant Epilepsy.
Antiepileptic drugs afford good seizure control for approximately 70% of individuals with epilepsy. Epilepsy surgery is extremely helpful for appropriate individuals with drug resistance. Since antiquity, trephination was a crude and invasive technique to manage epilepsy. The late 1800s saw the advent of a more evidence-based approach with attempts to define seizure foci and determine areas of function. Seizure localization initially required direct brain stimulation during surgery before resection. Fortunately, improved knowledge of seizure semiology and advancements in preoperative investigations have enabled epilepsy specialists to better analyze the benefit of seizure reduction versus risk of functional harm. This preoperative phase and the investigative techniques used to analyze surgical candidacy will be discussed in this article.


Role of central and peripheral signals in force sensation during fatigue.
Five subjects matched the force of a sustained isometric contraction with a contraction of the contralateral muscle. Estimates of the sustained constant forces increased with time despite the direction to disregard the increased effort associated with the fatiguing contraction. These instructions did not produce a noticeable dissociation between effort and achieved force during fatigue as had previously been reported during paresis and tendon vibration.


Preliminary Outcomes of Different Tactics of Ureteral Stent Placement in Patients with Ureteral Stricture Undergoing Balloon Dilatation: Experience from a Large-Scale Center.
Our aim is to demonstrate the optimal number of ureteral stent placements in patients with a ureteral stricture (US) after balloon dilatation (BD). A retrospective analysis of 213 patients who underwent BD from 2011 to 2019 was conducted. All statistical analyses were completed by software SPSS 25.0. Of the patients enrolled, 119 were males and 94 were females. The average age was 44.71 years. One month after stent removal, the overall success rate of ureteral stent placement was 76.99%, and the success rates of single, double, and triple stent groups were 81.7%, 70.3%, and 79.3%, respectively. Six months after stent removal, the overall success rate was 61.9%, and the success rates of the three groups were 61.7%, 52.7%, and 74.1%, respectively. Twelve months after stent removal, the overall success rate was 55.9%, and the success rates of the three groups were 51.9%, 48.6%, and 70.7%, respectively. During indwelling of the stents, the proportions of severe bladder irritation symptoms in the three groups were 13.6%, 16.2%, and 20.7%, respectively. Multivariate analysis indicated the length of US and the time and number of ureteral stent placements were independent risk factors of the treatment effect at 6 months and 12 months after stent removal. Patients in the triple stent group had a better prognosis when compared to those in the single or double stent group. The long-term effect of three stents was better than that of single and double stents, but the success rate of treatment reduced gradually over time.


Effect of Substrate Surface Roughening on the Capacitance and Cycling Stability of Ni(OH)2 Nanoarray Films.
The effect of substrate surface roughening on the capacitance of Ni(OH)2/NiOOH nanowall array samples produced via chemical bath deposition for 2, 4, 6, 24 and 48 h on an as-received stainless steel substrate and the same substrate after sandblasting has been investigated. Symmetric cells were subjected to 120,000 charge-discharge cycles to access changes in their capacitance. Specific capacitances were derived from cyclic voltammetry and charge-discharge cycling under a three electrode setup. Substrate roughening significantly increases the capacitance of symmetric cells and film stability since film exfoliation does not occur to the same degree as on the as-received substrate. Interestingly, films deposited on a roughened substrate for 6, 24 and 48 h also exhibit self-recovery of capacitance, which could be related to an electrodissolution-electrodeposition effect. With the use of a roughened substrate, the thinnest film gives the highest specific capacitance, 1456 F g-1, whilst the thickest one shows the highest areal capacitance, 235 mF cm-2, after 20,000 cycles. These results reveal the promise of surface roughening toward increasing the capacitance and stability of Ni(OH)2/NiOOH films.


Patent foramen ovale closure using a bioabsorbable closure device: safety and efficacy at 6-month follow-up.
The aim of this study was to assess the mid-term safety and efficacy of percutaneous patent foramen ovale (PFO) closure using a bioabsorbable device (BioSTAR, NMT Medical, Boston, Massachusetts). Closure of PFO in patients with cryptogenic stroke has proven to be safe and effective using different types of permanent devices. All consecutive patients who underwent percutaneous PFO closure with the bioabsorbable closure device between November 2007 and January 2009 were included. Residual shunt was assessed using contrast transthoracic echocardiography. Sixty-two patients (55% women, mean age 47.7 ± 11.8 years) underwent PFO closure. The in-hospital complications were a surgical device retrieval in 2 patients (3.2%), device reposition in 1 (1.6%), and a minimal groin hematoma in 6 patients (9.7%). The short-term complications at 1-month follow-up (n = 60) were a transient ischemic attack in the presence of a residual shunt in 1 patient and new supraventricular tachycardia in 7 patients (11.3%). At 6-month follow-up (n = 60), 1 patient without residual shunt developed a transient ischemic attack and 1 developed atrial fibrillation. A mild or moderate residual shunt was noted in 51.7%, 33.9%, and 23.7% after 1-day, 1-month, and 6-month follow-up, respectively. A large shunt was present in 8.3%, 3.4%, and 0% after 1-day, 1-month, and 6-month follow-up. Closure of PFO using the bioabsorbable device is associated with a low complication rate and a low recurrence rate of embolic events. However, a relatively high percentage of mild or moderate residual shunting is still present at 6-month follow-up.


Promoter variations in a homeobox gene, BnA10.LMI1, determine lobed leaves in rapeseed (Brassica napus L.).
BnA10.LMI1 positively regulates the development of leaf lobes in Brassica napus, and cis-regulatory divergences cause the different allele effects. Leaf shape is an important agronomic trait, and large variations in this trait exist within the Brassica germplasm. The lobed leaf is a unique morphological characteristic for Brassica improvement. Nevertheless, the molecular basis of leaf lobing in Brassica is poorly understood. Here, we show that an incompletely dominant locus, BnLLA10, is responsible for the lobed-leaf shape in rapeseed. A LATE MERISTEM IDENTITY1 (LMI1)-like gene (BnA10.LMI1) encoding an HD-Zip I transcription factor is the causal gene underlying the BnLLA10 locus. Sequence analysis of parental alleles revealed no sequence variations in the coding sequences, whereas abundant variations were identified in the regulatory region. Consistent with this finding, the expression levels of BnLMI1 were substantially elevated in the lobed-leaf parent compared with its near-isogenic line. The knockout mutations of BnA10.LMI1 gene were induced using the CRISPR/Cas9 system in both HY (the lobed-leaf parent) and J9707 (serrated leaf) genetic backgrounds. BnA10.LMI1 null mutations in the HY background were sufficient to produce unlobed leaves, whereas null mutations in the J9707 background showed no obvious changes in leaf shape compared with the control. Collectively, our results indicate that BnA10.LMI1 positively regulates the development of leaf lobes in B. napus, with cis-regulatory divergences causing the different allelic effects, providing new insights into the molecular mechanism of leaf lobe formation in Brassica crops.


Retrospective angiographic study to determine the effect of atherosclerotic stenoses of upstream arteries on the degree of atherosclerosis in distal vascular territories.
Experimental coarctation of the aorta prevents the development of downstream atherosclerosis. The aim of this study was to find out whether or not atherosclerotic stenoses protect distal vascular territories from developing atherosclerosis in humans. A total of 2125 vascular segments from angiographies of 101 patients were evaluated by calculating the maximum degree of stenosis (NASCET criteria), the degree of calcification, the degree of collaterals and the Friesinger score. Stenosis ≥30-49% was found in 685 vascular segments (32.2%), ≥50-69% in 490 (23.1%), ≥70-89% in 373 (17.6%) and ≥90% in 265 (12.5%). If a stenosis of at least ≥70-89% was present in the common iliac, the external iliac or the common femoral artery, the degrees of stenosis distal to it were lower than those on the contralateral side (19.8±22.3% (CI 11.7 to 28.0) vs 25.2±20.7% (CI 21.2 to 29.1); Friesinger scores 1.1±1.2 (CI 0.6 to 1.5) vs 1.4±1.1 (CI 1.2 to 1.6); degrees of calcification 0.8±1.0 (CI 0.4 to 1.1) vs 1.2±1.1 (CI 1.2 to 1.6); p<0.05 each). This effect depended on the degree of proximal stenosis, but not on collaterals, and was most pronounced distal to stenoses of the common iliac, the superficial femoral and the popliteal artery. In regression models, stenoses of the pelvic arteries were shown to be an independent protective factor for the distal vascular territories. Atherosclerotic stenoses seem to protect distal vascular territories from developing atherosclerosis. The underlying pathophysiological mechanism of this phenomenon remains to be determined. It could be based on pulse pressure reduction.


Emotional availability in psychotherapy: the usefulness and validity of the emotional availability scales for analyzing the psychotherapeutic relationship.
The aim of this study was to assess whether a modified version of the Emotional Availability Scales (EAS), created to assess interaction quality between parents and children, could be applied to psychotherapy sessions and whether emotional availability (EA), as assessed by the modified EAS-T, was associated with client- and therapist-rated working alliance. EAS-T was used to assess 42 sessions from 16 therapies. The therapies came from the LURIPP project, comparing IPT with BRT for depressed clients. The results showed that sessions could be reliably rated with EAS-T. Most rating scales had acceptable variance. The client's perception of task alliance was associated with several of the EA subscales (sensitivity, nonhostility, responsiveness) assessed over therapies, whereas the perception of bond was associated with Structure on EAS.


Women with Cirrhosis: Prevalence, Natural History, and Management.
Cirrhosis is less frequent in women than in men, in large part due to the lower prevalence of hepatitis B, hepatitis C, and alcohol use in women. The most common causes of cirrhosis among women are hepatitis C, autoimmune etiologies, nonalcoholic steatohepatitis, and alcoholic liver disease. For most chronic liver diseases, the risk of progression to cirrhosis and rates of liver failure and hepatocellular carcinoma are lower in women than in men. Pregnancy is very infrequent in women with cirrhosis due to reduced fertility, but when it occurs, requires specialized management.


Inositol phospholipid-induced suppression of F-actin-gelating activity of smooth muscle filamin.
Filamin, a high molecular weight actin-binding protein, cross-links actin filaments and produces a gel composed of F-actin. The effects of polyphosphoinositides on the gelating activity of smooth muscle filamin were examined by measuring the low shear viscosity of the F-actin solutions containing filamin incubated with phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PIP), or phosphatidylinositol 4,5-bisphosphate (PIP2). Micelles of these inositol phospholipids bound to filamin inhibited the ability to form a gel of F-actin. The inhibiting activity of each phospholipid was in the following order, PIP2 greater than PIP greater than PI. The F-actin binding assay of filamin revealed that the inhibition of F-actin-gelation resulted in the loss of the F-actin-binding activity of filamin. Thus, polyphosphoinositides may play important roles in regulating the gelating activity of filamin.


Genomic evolution of Vibrio cholerae.
Vibrio cholera, the causal agent of cholera, also occupies an autochthonous aquatic inhabitant. The current, seventh cholera pandemic is linked to O1 El Tor biotype and O139 serogroups. In the last decades, we have witnessed a shift involving genetically and phenotypically varied pandemic clones in Asia and Africa. Recent comparative genomic studies have identified a large 'mobilome', or composed of mobile genomic islands in V. cholerae. All seventh pandemic isolates have highly related genome sequences, but they can be differentiated by set of these genomic islands. A consequence of the extensive lateral gene transfer is that classically important diagnostic markers, such as serotype and biotype, are not reliable and new methods based on genomic sequences are required.


Susceptibility of human lymphoblastoid B-cell line CE to HIV1 infection.
In this preliminary report, we provide evidence that the human B-lymphoblastoid cell line (LCL) CE, bone-marrow-derived, previously reported to be permissive to hepatitis C virus, is also permissive to HIV1 infection. HIV1 genomes were detectable in cell supernatants, virus RNA transcripts and proviral DNAs in cell extracts at different times post-infection. Therefore, we propose this LCL cell line as a tool for exploring the mutual interactions of the two viruses in double-infected cells.


A multivariate phenetic approach to neuronal nuclei resemblances across species, with examples from three regions of cerebral cortex of a mammal, a bird and a reptile.
In order to test the assumed homology between three examples of cortical cerebral architecture corresponding to three species of mammals, birds and reptiles respectively, a method arising from the quantitative standpoint of the concept of homology has been utilized. For this purpose, data corresponding to randomly selected neurons were analysed by means of multivariate techniques such as principal component, principal co-ordinates and hierarchical cluster analyses since on each neuron a set of nineteen variables, chosen as a definition of its dendritic morphology, was measured. This method has made it possible both to discern the neuron forms which are responsible for the discrimination between the three cortical nuclei studied and to show by setting up a discriminant index, the degree of overall similarity between such nuclei. These two findings provide evidence against both the fibrous connection criterion with which some modern neurobiologists ascertain homologs and the categorical concept of homology.


Interaction of new anthracycline antibiotics with DNA. Effects on nucleic acid synthesis and binding to DNA.
The effects of various new anthracycline antibiotics on DNA and RNA synthesis were studied using DNA polymerase I (EC 18.104.22.168), RNA polymerase (EC 126.96.36.199) obtained from Escherichia coli and reverse transcriptase obtained from avian myeloblastosis virus. Aclacinomycin A, its analogues, baumycins A1 and A2, adriamycin and daunomycin showed potent inhibitory effects on these polymerases, with calf thymus DNA as template, with IC50 values of 10-30 microM. With poly(rA) x d(pT)10 as template for reverse transcriptase, aclacinomycin A and daunomycin showed IC50 values higher than 500 microM. Baumycins B1, B2, C1, and C2 showed high IC50 values on three polymerases. Addition of excess template DNA to the reaction mixture reversed the inhibitory effect of anthracyclines. Addition of calf thymus DNA to anthracyclines caused a bathochromic and hypochromic change in the visible spectrum. Apparent binding constant for aclacinomycin A, its analogues, and adriamycin were in the range of (1-2) X 10(6) M-1. Aclacinomycin A and adriamycin also bind to heat denatured DNA, but not strongly to yeast RNA. From these results, the structure-activity relationships of new anthracyclines on DNA binding and polymerase reactions are discussed.


Low anterior resection with anastomosis by endorectal pull-through. Another look at Black's operation.
The type of endorectal pull-through described by Black was evaluated as an alternative method of anastomosis in 11 anterior resections in which anastomosis from above was impossible. The method is attractive from the standpoint of function because it preserves the distal rectum and leaves the anus intact. Technical points important to success are complete mobilization of the descending colon to allow the distal descending colon to be used for the pull-through and prophylactic dilatation of the early stenosis, which is characteristic of this type of anastomosis.


'That might be a bit sexy for somebody your age': Older adult sexual health conversations in primary care.
Many older adults are sexually active, and STIs are rising amongst this cohort. In primary care, sexual health discussions are limited as health-care practitioners commonly assume older patients aged 60+ are not sexually active or are unwilling to discuss sex. Studies have either examined patient or clinician views, but not both. This study investigates sexual health discussions in general practice. It is unique in that it sought perspectives of different groups: older patients, health-care professionals and key informants. Qualitative interviews revealed that older patients expect clinicians to bring up sexual concerns, whereas clinicians prefer older patients to do so. A simple electronic solution to circumvent this impasse was suggested and discussed. Older adults would like to discuss sexual concerns with their health-care providers. Given the rising rates of STIs in later life, sexual health discussions with older patients must become part of routine care.


The extensor carpi radialis intermedius tendon.
I examined 312 arms from 156 cadavers in the anatomy laboratory of Loma Linda University to find the incidence of the extensor carpi radialis intermedius tendon. I found 29 bodies (12%) that had a good extensor carpi radialis intermedius. In 17 of these 29 bodies, an extra tendon was found bilaterally. Thirty-two extensor carpi radialis intermedius tendons were suitable for transfer operations, and seven were unacceptable. One must be careful to differentiate between a true extensor carpi radialis intermedius tendon and accessory tendinous bands. The relatively high incidence rate and percentage of tendons suitable for transfer operations make this tendon potentially valuable in treating severe quadriplegia with tendon transfers. It can be used successfully for thumb opposition, to motor the flexor pollicis longus, or as a motor for the extensor pollicis longus of the thumb.


Soluble fiber intake at a dose approved by the US Food and Drug Administration for a claim of health benefits: serum lipid risk factors for cardiovascular disease assessed in a randomized controlled crossover trial.
The US Food and Drug Administration (FDA) approved health claims for 2 dietary fibers, beta-glucan (0.75 g/serving) and psyllium (1.78 g/serving), on the assumption that 4 servings/d would reduce cardiovascular disease risk. We assessed the efficacy of this dose of fibers in reducing serum lipid risk factors for cardiovascular disease. Sixty-eight hyperlipidemic adults consumed a test (high-fiber) and a control low-fat (25% of energy), low-cholesterol (<150 mg/d) diet for 1 mo each in a randomized crossover study. The high-fiber diet included 4 servings/d of foods containing beta-glucan or psyllium that delivered 8 g/d more soluble fiber than did similar, unsupplemented foods in the control diet. Fasting blood samples and blood pressure readings were obtained at baseline and weeks 2 and 4, and the subjects' weight was monitored weekly. Compared with the control diet, the high-fiber diet reduced total cholesterol (2.1 +/- 0.7%; P = 0.003), total:HDL cholesterol (2.9 +/- 0.8%; P = 0.001), LDL:HDL cholesterol (2.4 +/- 1.0%; P = 0.015), and apolipoprotein B:A-I (1.4 +/- 0.8%; P = 0.076). Applying the Framingham cardiovascular disease risk equation to the data confirmed a reduction in risk of 4.2 +/- 1.4% (P = 0.003). Small reductions in blood pressure were found after both diets. The subjects reported no significant differences in palatability or gastrointestinal symptoms between the diets. The reduction in serum lipid risk factors for cardiovascular disease supports the FDA's approval of a health claim for a dietary fiber intake of 4 servings/d. Although relatively small in terms of patient treatment, the reduction in cardiovascular disease risk is likely to be significant on a population basis.


Free erythrocyte porphyrins in cord blood.
Red cell free erythrocyte porphyrin determinations were performed on cord blood specimens from 236 term infants and on capillary blood specimens from 63 preterm infants weighing less than 1,500 gm, during the first week of life. These results were contrasted with those obtained from 398 normal infants and children ages 1 to 6 years. The mean FEP value for the infants was significantly higher than that observed in the normal control subjects. In 10.5% of the term infants and 15.9% of the preterm infants, values in excess of 120 microgram/dl RBCs, the highest value recorded in the normal subjects, were observed. Elevations in FEP values were not related to either blood lead concentration or hematocrit levels in the infants. Infants with elevated FEP values were found to have lower serum iron and transferrin saturation values than did infants with low FEP values. These findings suggest that elevations in cord blood FEP values may indicate a state of relative iron deficiency present at birth.


Diffuse cerebrospinal gliomatosis: clinical and radiological findings.
Diffuse cerebrospinal gliomatosis is extremely rare. We report the case of a 47-year-old man who presented with clinical features of intracranial hypertension. He developed ascending paraplegia and died. This latter clinical feature has not previously been reported. Clinical features and diagnostic difficulties are discussed.


A preliminary trial of an online dissonance-based eating disorder intervention.
We conducted a controlled randomized preliminary trial of an expanded online version of the Body Project (n = 46) compared to an assessment-only control condition (n = 36) via a longitudinal design (baseline, postintervention, 2-month follow-up) in a community sample of women (N = 82) with clinical (n = 53) and subclinical (n = 29) eating disorder symptoms. The traditional content of the Body Project was modified to include verbal, written, and behavioral exercises designed to dissuade objectification and maladaptive social comparison and adapted to an online format. Body dissatisfaction, self-esteem, self-objectification, thin-ideal internalization, maladaptive social comparison, trait anxiety, positive affect, negative affect, and eating disorder symptomatology were evaluated in the control and the online expanded Body Project condition at baseline, postintervention, and 2-month follow-up. A 2 (condition: online expanded Body Project, control) × 3 (time: baseline, postintervention, 2-month follow-up) mixed factorial multivariate analysis of variance (MANOVA) was conducted to examine statistically significant group differences. As predicted, results indicated a statistically significant condition × time interaction. Participants in the expanded online Body Project condition showed significant reductions in eating disorder symptoms and several associated psychological risk correlates from baseline to postintervention and follow-up; contrary to predictions, eating disorder symptoms and risk correlates were not significantly lower in the online expanded Body Project condition compared to the waitlist control condition at postintervention or 2-month follow-up.


Retraction: Botulinum Toxin for the Treatment of Hyperfunctional Lines of the Forehead.
[This retracts the article on p. 276 in vol. 5, PMID: 26312226.].


The JNK, ERK and p53 pathways play distinct roles in apoptosis mediated by the antitumor agents vinblastine, doxorubicin, and etoposide.
Assessment of specific apoptosis and survival pathways implicated in anticancer drug action is important for understanding drug mechanisms and modes of resistance in order to improve the benefits of chemotherapy. In order to better examine the role of mitogen-activated protein kinases, including JNK and ERK, as well as the tumor suppressor p53, in the response of tumor cells to chemotherapy, we compared the effects on these pathways of three structurally and functionally distinct antitumor agents. Drug concentrations equal to 50 times the concentration required to reduce cell proliferation by 50% were used. Vinblastine, doxorubicin, or etoposide (VP-16) induced apoptotic cell death in KB-3 carcinoma cells, with similar kinetic profiles of PARP cleavage, caspase 3 activation, and mitochondrial cytochrome c release. All three drugs strongly activated JNK, but only vinblastine induced c-Jun phosphorylation and AP-1 activation. Inhibition of JNK by SP600125 protected cells from drug-induced cytotoxicity. Vinblastine caused inactivation of ERK whereas ERK was unaffected in cells exposed to doxorubicin or VP-16. Inhibition of ERK signaling by the MEK inhibitor, U0126, potentiated the cytotoxic effects of vinblastine and doxorubicin, but not that of VP-16. Vinblastine induced p53 downregulation, and chemical inhibition of p53 potentiated vinblastine-induced cell death, suggesting a protective effect of p53. In contrast, doxorubicin and VP-16 induced p53, and inhibition of p53 decreased drug-induced cell death, suggesting a pro-apoptotic role for p53. These results highlight the differential roles played by several key signal transduction pathways in the mechanisms of action of key antitumor agents, and suggest ways to specifically potentiate their effects in a context-dependent manner. In addition, the novel finding that JNK activation can occur without c-Jun phosphorylation or AP-1 activation has important implications for our understanding of JNK function.


Delineating implicit and explicit processes in neurofeedback learning.
Neurofeedback allows humans to self-regulate neural activity in specific brain regions and is considered a promising tool for psychiatric interventions. Recently, methods have been developed to use neurofeedback implicitly, prompting a theoretical debate on the role of awareness in neurofeedback learning. We offer a critical review of the role of awareness in neurofeedback learning, with a special focus on recently developed neurofeedback paradigms. We detail differences in instructions and propose a fine-grained categorization of tasks based on the degree of involvement of explicit and implicit processes. Finally, we review the methods used to measure awareness in neurofeedback and propose new candidate measures. We conclude that explicit processes cannot be eschewed in most current implicit tasks that have explicit goals, and suggest ways in which awareness could be better measured in the future. Investigating awareness during learning will help understand the learning mechanisms underlying neurofeedback learning and will help shape future tasks.


Enhanced TCR footprint by a novel glycolipid increases NKT-dependent tumor protection.
NKT cells, a unique type of regulatory T cells, respond to structurally diverse glycolipids presented by CD1d. Although it was previously thought that recognition of glycolipids such as α-galactosylceramide (α-GalCer) by the NKT cell TCR (NKTCR) obeys a key-lock principle, it is now clear this interaction is much more flexible. In this article, we report the structure-function analysis of a series of novel 6''-OH analogs of α-GalCer with more potent antitumor characteristics. Surprisingly, one of the novel carbamate analogs, α-GalCer-6''-(pyridin-4-yl)carbamate, formed novel interactions with the NKTCR. This interaction was associated with an extremely high level of Th1 polarization and superior antitumor responses. These data highlight the in vivo relevance of adding aromatic moieties to the 6''-OH position of the sugar and additionally show that judiciously chosen linkers are a promising strategy to generate strong Th1-polarizing glycolipids through increased binding either to CD1d or to NKTCR.


A phase I-II trial of multimodality management of bulky gynecologic malignancy. Combined chemoradiosensitization and radiotherapy.
Between December 1983 and December 1987, there were 44 patients with bulky, nonresectable squamous cell carcinomas of the gynecologic tract (cervix, 36; vagina, eight) who were treated with concomitant chemotherapy and radiotherapy. Chemotherapy consisted of 5-fluorouracil (5-FU) 1g/m2 given by continuous intravenous infusion on days 1 through 4 and mitomycin C 10 mg/m2 given intravenously on day 1. External-beam irradiation was started on day 1 with a total calculated dose of 5000 cGy in 25 fractions employed. This was followed by brachytherapy. With a mean follow-up of 30.3 months and a median of 28 months, local control has been achieved in 32 of 44 patients (73%). The overall response rate was 88% (3-month partial response, 43%; 3-month complete response, 45%; 8-month partial response, 15%; 8-month complete response, 73%). Analysis of complications by Radiation Therapy Oncology Group (RTOG) criteria did not demonstrate an increase in acute or late complications.


Are Primary Trauma Care (PTC) courses beneficial in low- and middle-income countries - A systematic review.
Injuries remain an important public health concern, resulting in considerable annual morbidity and mortality. In low- and middle-income countries (LMICs), the lack of appropriate infrastructure, equipment and skilled personnel compound the burden of injury, leading to higher mortality rates. As Advanced Trauma Life Support (ATLS) courses remain uneconomical and inappropriate in LMICs, the Primary Trauma Care (PTC) course was introduced to provide an alternative that is both sustainable and appropriate to local resources. A systematic review was performed in May 2019, utilising MEDLINE, EMBASE, Cochrane Library and Google Scholar. All studies reporting patient related outcomes (mortality and morbidity rates) and course participant related outcomes (knowledge, confidence and skills) in LMICs were included. PRISMA guidelines were adhered to throughout. Nine observational studies were identified (Level 3 evidence). Six studies reported improved knowledge in injury management post-PTC course (p < 0.05). Two studies reported improvements in confidence (p < 0.05) and one on skill attainment (p < 0.0001). One study reported a reduction in mortality rates post-PTC course (p < 0.01). Departmental, institutional and personal improvements may occur in clinical practice as a result of formal PTC training of trauma team members in LMICs. Further high-quality research is needed to evaluate this course's effects on observed change in clinical practice and patient outcomes. This may require long-term observational and epidemiological studies to assess improvements in morbidity and mortality. PROSPERO Registration Number: CRD42019133986.


Nonsurgical treatment of incipient and hidden caries.
Traditionally, dentists have been trained in the surgical model for caries management whereby detection is akin to diagnosis. This model unfortunately has been translated to patient expectations. Nevertheless, a growing body of clinical evidence suggests that noncavitated lesions, even those extending into dentin, can be managed by nonsurgical means with an expectation for remineralization.


α-Haloacetophenone and analogues as potential antibacterial agents and nematicides.
A series of α-haloacetophenones and analogues were synthesized. The bioassays show that some target compounds have good antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac) and Meloidogyne incognita (M. incognita). Especially, the compound 24 has good in vitro and in vivo antibacterial activities against Xoo, the EC50 value, curative and protection activities are 0.09 mg/L, 48.9%, and 52.3%, respectively, which are better than the thiodiazole copper and bismerthiazol. Meanwhile, the compound 24 has good in vitro antibacterial activity against Xac, and has an EC50 value of 1.6 mg/L. Moreover, the compound 19 exhibits good nematicidal activity M. incognita, with the LC50 value of 1.0 mg/L, which is better than the positive control avermectin. In addition, the compound 24 can inhibit the formation of extracellular polysaccharide and biofilm of Xoo, and change the permeability of cell membrane. α-haloacetophenone and analogues have the advantages of simple structure, high efficiency, broad spectrum of biological activity, and can be used as antibacterial agents and nematicides or lead compounds in the future.


Heat stability of lyophilized C1 inactivator concentrates.
Heat stability of lyophilized C1 inactivator (C1-INA) concentrates of intermediate and high purity has been investigated under several heat treatment protocols that include heating for 96 and 192 h at 68 degrees C and for 10 h at 80, 90 and 100 degrees C. Both types of concentrate showed high stability in functional activity, with not more than 5% loss in any of the time-temperature combinations evaluated. However, the C1-INA antigen from both concentrates showed small but progressive changes in crossed immunoelectrophoretic pattern, in proportion to the intensity of heat treatment. High-pressure size-exclusion chromatography revealed only minimal signs of aggregation in the high-purity concentrate, but a significant and progressive aggregation of nonspecific protein contaminants present in the intermediate-purity concentrate, making the high-purity concentrate preferable for heat treatment.


School factors associated with the provision of physical education and levels of physical activity among elementary school students in Ontario.
To explore school and student characteristics associated with the number of physical education (PE) classes that elementary students received and to determine whether these characteristics and amount of PE were associated with the physical activity (PA) levels of elementary students. Multi-level modeling with school-level (n = 30) and student-level (n = 2,447) questionnaire data from the PLAY-ON study was used to explore the school factors associated with the number of PE classes that students in grades 5 to 8 report receiving, and how these factors were associated with their PA. The Theories of Organizational Change served to operationalize the main school factors measured in this study and included assessments of: organizational climate (school practices related to PE or PA), organizational capacity (school ability to provide students with more PE or PA), and school PA/PE policies. The number of PE classes reported per week was higher in schools that had two PA facilities in addition to a gymnasium (β = 1.13, p = 0.048) and in schools with greater levels of parental involvement in school-based PA decisions and programs (β = 2.06, p = 0.001). However, students in schools that provided more intramural programs reported fewer PE classes than those without (β = -1.97, p < 0.001). The number of PE classes provided in the previous week was associated with greater odds of students being highly active compared to minimally active (OR = 1.14, p = 0.003). Organizational and structural factors within the school environment are related to the amount of PE that students receive at school. Strategies are required to resolve the resulting inequities.


Emotional support (giving or receiving) and risk of incident dementia: The Ohsaki Cohort 2006 Study.
Previous studies have suggested that emotional support may promote cognition; however, the effects of giving or receiving emotional support on incident dementia remain unclear. Therefore, we sought to investigate the relationship between emotional support (giving or receiving) and incident dementia. In December 2006, we conducted a prospective cohort study of 31,694 Japanese individuals aged ≥65 years who lived in Ohsaki City, Miyagi Prefecture, Japan. A self-reported questionnaire including items on emotional support and lifestyle factors was distributed. After excluding those who did not provide consent or responses to all items, 13,636 eligible responses were analyzed for this study. According to responses of "yes" or "no" for emotional support, we made two categories for both giving (gave or did not give) and receiving (received or did not receive) emotional support. Furthermore, we combined giving and receiving emotional support into four categories ("giving = no & receiving = no", "giving = no & receiving = yes", "giving = yes & receiving = no", "giving = yes & receiving = yes"). Data on incident dementia were retrieved from the Long-term Care Insurance Database in which participants were followed up for 5.7 years. Using multivariate Cox proportional hazards models, we found that compared with participants who did not give emotional support to others, those who did give had a lower risk of dementia (multivariate-adjusted hazard ratio [HR]: 0.61 (95% confidence interval [CI]: 0.52, 0.71)). However, a nonsignificant relationship was observed for receiving emotional support. Additionally, compared to "giving = no & receiving = no" for emotional support, "giving = no & receiving = yes" showed a higher risk of dementia (multivariate-adjusted HR: 1.51 [95% CI: 1.07, 2.14]).


Microbial characterization and hydrocarbon biodegradation potential of natural bilge waste microflora.
Shipping operations produce oily wastes that must be managed properly to avoid environmental pollution. The aim of this study was to characterize microorganisms occurring in ship bilge wastes placed in open lagoons and, particularly, to assess their potential to degrade polycyclic aromatic hydrocarbons (PAHs). A first-order kinetic was suitable for describing hydrocarbon biodegradation after 17 days of treatment. The calculated rate constants were 0.0668 and 0.0513 day(-1) with a corresponding half-life of 10.3 and 13.5 days for the aliphatic and aromatic hydrocarbon fractions, respectively. At day 17, PAH removal percentages were: acenaphtylene 100, fluorene 95.2, phenanthrene 93.6, anthracene 70.3, and pyrene 71.5. Methyl phenanthrene removals were lower than that of their parent compound (3-methyl phenanthrene 83.6, 2-methyl phenanthrene 80.8, 1-methyl phenanthrene 77.3, 9-methyl phenanthrene 75.1, and 2,7-dimethyl phenanthrene 76.6). Neither pure cultures nor the microbial community from these wastes showed extracellular biosurfactant production suggesting that the addition of an exogenously produced biosurfactant may be important in enhancing hydrocarbon bioavailability and biodegradation. DNA analysis of bilge waste samples revealed a ubiquitous distribution of the nahAc genotype in the dump pools. Although almost all of the isolates grew on naphthalene as sole carbon source, only some of them yielded nahAc amplification under the experimental conditions used. The variety of PAHs in bilge wastes could support bacteria with multiple degradation pathways and a diversity of catabolic genes divergent from the classical nah-like type.


The respiratory cytotoxicity of typical organophosphorus flame retardants on five different respiratory tract cells: Which are the most sensitive one?
Triphenyl phosphate (TPHP) is a frequently used flame retardant and indoor semi-volatile pollutant exposing humans with endocrinal disrupting effects. However, its respiratory tract toxicity remains unclear. Herein, we mainly focused on exploring the cytotoxicity of TPHP to the cells from five different parts of the human respiratory tract (from top to bottom): human nasal epithelial (HNEpC) cells, human bronchial epithelial (16HBE) cells, normal nasopharyngeal epithelial (NP69) cells, human lung epithelial cells (Beas-2B) cells, and human lung fibrocells (HFL1 cells) cells. The cell viability, micronucleus induction, endoplasmic reticulum stress gene, intracellular Ca2+ concentration, mitochondrial membrane potential (MMP) were investigated in short-term as well as extended exposure of TPHP. HFL1 and HNEpC cells were found to be irreversible damage, while other three type cells achieved homeostasis through self-rescue. Moreover, expression of downstream genes of Nrf2 signaling pathway were upregulated for 1.3-7.0 times and glutathione detoxification enzyme activity changed for 2-10 (U/mg protein) in HNEpC cells. Furthermore, the vascular endothelial growth factor (VEGF), a disease-related factor, increased 1.0-3.5-fold in HNEpC cells. RNA-sequencing results suggested that protein linkage recombination, molecular function regulation and metabolic processes signal pathway were all affected by TPHP exposure in HNEpC. This is a first report to compare respiratory cytotoxicity in whole human respiratory tract under OPFR exposure and found HNEpC cells were the most sensitive target of TPHP. Molecular biological mechanisms uncovered that TPHP exposure in HNEpC can induce the activation of MAPK signal pathway and demonstrate potential respiratory growth differentiation and stress disorder in human nasal cells upon TPHP exposure.


Regional heterogeneity of substance P-induced endothelium-dependent contraction, relaxation, and -independent contraction in rabbit pulmonary arteries.
The present study examined whether substance P (SP)-induced endothelium-dependent TXA(2)-mediated contraction (EDC), nitric oxide (NO)-mediated relaxation (EDR), and endothelium-independent contraction (EIC) are different between the rabbit proximal and distal intrapulmonary arteries. The helically cut strips of isolated proximal and distal arteries were fixed vertically between hooks in organ bath, and changes in isometric tension were measured. SP-induced EDC was greater in the distal than proximal arteries, and EDR was greater in the proximal than distal arteries. However, under the complete blockade of NK(2) receptors and NO production, SP (10(-9)-3x10(-7) M)-induced EDC did not differ between proximal and distal arteries. Under the complete blockade of NK(2) receptors and TXA(2) production, SP (3x10(-10)-3x10(-8) M)-induced EDR was greater in the proximal than distal arteries. Neither contraction induced by U-46619, a TXA(2) agonist, nor relaxation by sodium nitroprusside, an NO donor, was different between both portions of the arteries. Both ionomycin (10(-8) M)- and l-arginine (1 mM)-induced EDRs were also significantly greater in the proximal than distal arteries. Under the blockade of NK(1) receptors and NO and TXA(2) production, SP (10(-7) M)-induced EIC was greater in the distal than proximal arteries. In summary, the capacity for NO production is higher in the proximal than distal arteries, resulting in SP-induced higher EDR and lower EDC in the proximal arteries. These regional differences in responses to SP may play important roles in maintaining the homogenous distribution of blood flow in the lung.


Mixed Purpuric and Maculopapular Lesions in a Patient with COVID-19: A Case Report.
The coronavirus disease of 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 is a global pandemic that expresses itself with a wide variety of presenting symptoms in patients. There is a paucity of literature describing the dermatologic manifestations of the virus, particularly in the United States. Here we present a case of COVID-19 that manifested with a purpuric rash on the lower extremities and a maculopapular eruption on the abdomen in a patient in acute diabetic ketoacidosis and normal platelet count. The reported presenting symptoms of patients with COVID-19 vary greatly. This is the first documented case of COVID-19 presenting with mixed cutaneous manifestations of a purpuric as well as maculopapular rash. The cutaneous lesions associated with the COVID-19 infection may mimic or appear similar to other well-known conditions. We illustrate a case of COVID-19 infection presenting with purpuric rash on the lower extremities and a maculopapular rash on the abdomen.


Operationalizing an open-source dashboard for communicating results of wastewater-based surveillance.
COVID-19 saw the expansion of public health tools to manage the pandemic. One tool that saw extensive use was the public health dashboard, web-based visualization tools that communicate information to users in easy-to-read graphics. Dashboards were widely used prior to the pandemic, but COVID-19 saw expanded use and development. To date, dashboards have become an important part of public health surveillance programs around the world helping decisionmakers use data to evaluate different public health metrics including caseloads, hospitalizations, and environmental surveillance results from testing wastewater. Wastewater surveillance provides community-based, spatially relevant data on disease trends within communities to assess the scale of infection in a region, which makes it an excellent candidate for dashboard development to improve public health. We developed a dashboard for New York State's wastewater surveillance program using open-source, reproducible web programming. The dashboard we developed has been used for the COVID-19 response in New York, and our methods can be adapted to other programs and pathogens. We provide:•descriptions of how the dashboard was developed and maintained•specific guidance for reproducing our dashboard in other areas and for other pathogens•fully reproducible code with step-by-step instructions for researchers and professionals to make their own data dashboards.


Defining optimal thresholds for digital Brix refractometry to determine IgG concentration in ewe colostrum and lamb serum in Scottish lowland sheep flocks.
This research aimed to define thresholds for ewe colostrum and lamb serum Brix refractometer measurements in lowland Scottish sheep. This would facilitate the use of this convenient, sheep-side test, enabling quick and accurate identification of poor quality colostrum and prevention of failure of transfer of passive immunity (FTPI) in lambs. Secondary aims were to identify risk factors for poor colostrum quality and FTPI in lambs. Serum samples (n = 233) were collected from lambs between 24 and 48hrs after birth, from four lowland Scottish meat sheep farms. Pre-suckle colostrum samples (n = 112) were also collected from ewes on two of these farms. Farmers provided information on litter size, ewe body condition score, ewe breed and dystocia. Duplicate digital Brix refractometer measurements were compared with immunoglobulin G (IgG) radial immunodiffusion (RID) testing for all colostrum and serum samples. Receiver operating characteristic (ROC) curves were used to redefine thresholds for Brix testing in colostrum and serum. Linear regression models were constructed with colostrum and serum IgG concentration as the outcomes of interest. Colostrum and serum IgG concentrations were highly variable. The prevalence of inadequate colostrum quality (using <50 g/L IgG on RID) was 4.5% (95% CI = 1.5 - 10.1) and the prevalence of FTPI (using <15 g/L IgG in serum on RID) was 7.73% (95% CI = 4.64-11.93). A ewe's colostrum IgG concentration was significantly and positively associated with the serum IgG concentration of her lamb(s) (p = 0.02). ROC analysis defined a Brix threshold for adequate colostrum quality of > 22.10% (sensitivity 80% (95%CI=28.4-99.5), specificity 90% (95%CI=82.3-94.8)). ROC analysis defined a Brix threshold for serum of > 8.65% for adequate passive transfer of immunity in Scottish lambs (sensitivity 94% (95%CI=72.7-99.8), specificity 82% (95%CI=76.6-87.2)). To optimise passive transfer of immunity in lambs, we suggest that ewe colostrum Brix measurements be defined as 'poor' (<22%); 'fair' (22-26%) and 'good' (>26%); and lamb serum as 'poor' (<8%); 'fair' (8-9%) and 'good' (>9%). It is recommended that these tests are used as for flock screening, using samples from multiple animals.


ProbIDtree: an automated software program capable of identifying multiple peptides from a single collision-induced dissociation spectrum collected by a tandem mass spectrometer.
In MS/MS experiments with automated precursor ion, selection only a fraction of sequencing attempts lead to the successful identification of a peptide. A number of reasons may contribute to this situation. They include poor fragmentation of the selected precursor ion, the presence of modified residues in the peptide, mismatches with sequence databases, and frequently, the concurrent fragmentation of multiple precursors in the same CID attempt. Current database search engines are incapable of correctly assigning the sequences of multiple precursors to such spectra. We have developed a search engine, ProbIDtree, which can identify multiple peptides from a CID spectrum generated by the concurrent fragmentation of multiple precursor ions. This is achieved by iterative database searching in which the submitted spectra are generated by subtracting the fragment ions assigned to a tentatively matched peptide from the acquired spectrum and in which each match is assigned a tentative probability score. Tentatively matched peptides are organized in a tree structure from which their adjusted probability scores are calculated and used to determine the correct identifications. The results using MALDI-TOF-TOF MS/MS data demonstrate that multiple peptides can be effectively identified simultaneously with high confidence using ProbIDtree.


Automated regular boluses for epidural analgesia: a comparison with continuous infusion.
Intermittent epidural bolus dosing is a method of drug delivery that can prolong the duration of labour analgesia induced by a combined spinal epidural (CSE). In this randomized, double-blinded study, we compared the analgesic efficacy of two drug delivery systems: regular intermittent epidural boluses and continuous epidural infusion and assessed the incidence of breakthrough pain after CSE. With the approval of the Hospital Ethics Committee, we recruited 60 parturients into this randomized controlled trial. A CSE was performed with intrathecal fentanyl 25 mug in all patients. The parturients were then randomly allocated into two groups. The infusion group received a continuous epidural infusion of levobupivacaine 0.1% with fentanyl 2 microg/mL at a rate of 10 mL/h. The bolus group received 5-mL epidural boluses every half hour. The sample size was computed to detect a 40% reduction in the rate of breakthrough pain. The bolus group had a lower incidence of breakthrough pain than the infusion group (10% vs. 37%, P < 0.05). The bolus group also had significantly higher satisfaction scores for labour analgesia: 97+/-8 (mean+/-SD) vs. 89+/-7 (P < 0.05). Automated regular bolus delivery of epidural analgesia when compared with continuous infusion decreased the incidence of breakthrough pain and increased maternal satisfaction. In a busy obstetric unit, this may also serve to decrease the anesthetists' workload.


The serological responses to acute exercise in humans reduce cancer cell growth in vitro: A systematic review and meta-analysis.
We systematically reviewed and meta-analyzed the effects of acute exercise-conditioned serum on cancer cell growth in vitro. Five literature databases were systematically searched for studies that measured cancer cell growth after exposure to human sera obtained before and immediately after an acute bout of exercise. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were pooled using a three-level random-effects model. Meta-regressions were also performed with participant age and disease status, exercise type, cell line TP53 status, and serum incubation time entered as covariates. Seven studies met the inclusion criteria encompassing a total of 21 effect estimates and 98 participants. Exercise-conditioned serum significantly reduced cancer cell growth compared with preexercise serum (SMD = -1.23, 95% CI: -1.96 to -0.50; p = .002; I2 = 75.1%). The weighted mean reduction as a percentage of preexercise values was 8.6%. The overall treatment effect and magnitude of heterogeneity were not statistically influenced by any covariate. There were concerns regarding the risk of bias within individual studies and Egger's test of the intercept showed evidence of small study effects (β = -3.6, p = .004). These findings provide in vitro evidence that the transient serological responses to acute exercises reduce cancer cell growth, although many questions remain regarding the underlying mechanistic pathways and potential effect modifiers. To strengthen this evidence-base, future studies should seek to reduce the risk of bias by using more rigorous experimental designs, and consider using 3D cell culture models to better replicate in vivo tumor conditions. PROSPERO registration: CRD42020161333.


[Isolation and identification of oral spirochaetes and Fusobacterium in juvenile periodontitis].
Periodontal pocket specimens of 40 juveniles periodontitis (JP) and specimens from gingival sulcus in 40 normal juveniles (NP) were examined. 25 strains of anaerobic oral spirochaete (62.5%) (17 strains were Treponema microdentium, 3 strains macrodentium, 2 strains T orale, 3 strains Borrelia) and 21 strains of fusobacterium were isolated in 40 JP. In 40 NP, 2 strains of spirochaetes (5%) and 3 strains fusobacterium (7.5%) were found. This study shows that there is a relationship between the infection of spirochaeta, fusobacterium and JP.


Modulation of the stress response in wild fish is associated with variation in dissolved nitrate and nitrite.
Disruption of non-reproductive endocrine systems in wildlife by chemicals has received little attention but represents a potentially significant problem. Nitrate is a major anthropogenic contaminant in the freshwater aquatic environment and has been identified as a potential disrupter of endocrine function in aquatic animals. This study was conducted to investigate the relationship between the function of the neuroendocrine stress axis in fish and inorganic N loading along reaches of rivers receiving cumulative point source and diffuse chemical inputs. To accomplish this, the responsiveness of the stress axis, quantified as the rate of release of cortisol to water across the gills during exposure to a standardised stressor, was measured in three-spined sticklebacks (Gasterosteus aculeatus L.) resident at three sites on each of four rivers in north-west England. The magnitude of the stress response in fish captured at the sites furthest downstream on all rivers was more than twice that of fish captured at upstream sites. Site-specific variation in stress axis reactivity was better explained by between-site variation in concentrations of dissolved nitrate, nitrite, and ammonia than by the concentration of wastewater treatment works effluent. An increase in the magnitude of the stress response was seen among sticklebacks at sites where long-term averaged concentrations of NH3-N, NO3-N and NO2-N exceeded 0.6, 4.0 and 0.1 mg/L respectively. These data suggest that either (i) inorganic N is a better surrogate than wastewater effluent concentration for an unknown factor or factors affecting stress axis function in fish, or (ii) dissolved inorganic N directly exerts a disruptive influence on the function of the neuroendocrine stress axis in fish, supporting concerns that nitrate is an endocrine-modulating chemical.


[Effect of human regulatory myelopeptides on the elaboration of a factor inhibiting leukocyte migration].
Some properties of the regulatory peptides from human bone marrow have been investigated. It has been determined that the activity of the regulatory peptides was different in healthy donors and patients with agammaglobulinemia and paraproteinemia.


A treefrog's menu: Selection for an evening's meal.
Spodoptera (Lepidoptera) and Chauliognathus (Coleoptera) larvae are the two prey most frequently consumed by Hyla cinerea in the field, whereas Musca (Diptera) is the most consistently preferred food item offered in laboratory experiments in which prey are equally available. Three genus-specific variables influence prey selection: (1) prey length, (2) activity patterns exhibited by prey, and (3) the proportion of time devoted by prey to specific behavior patterns. The quality of feeding stimuli (estimated in captures/h) vary within the behavioral repertoire of a prey genus as well as among different prey performing similar activities.


Sustained Club Cell Injury in Mice Induces Histopathologic Features of Deployment-Related Constrictive Bronchiolitis.
Histopathologic evidence of deployment-related constrictive bronchiolitis (DRCB) has been identified in soldiers deployed to Southwest Asia. While inhalational injury to the airway epithelium is suspected, relatively little is known about the pathogenesis underlying this disabling disorder. Club cells are local progenitors critical for repairing the airway epithelium after exposure to various airborne toxins, and a prior study using an inducible transgenic murine model reported that 10 days of sustained targeted club cell injury causes constrictive bronchiolitis. To further understand the mechanisms leading to small airway fibrosis, a murine model was employed to show that sustained club cell injury elicited acute weight loss, caused increased local production of proinflammatory cytokines, and promoted accumulation of numerous myeloid cell subsets in the lung. Transition to a chronic phase was characterized by up-regulated expression of oxidative stress-associated genes, increased activation of transforming growth factor-β, accumulation of alternatively activated macrophages, and enhanced peribronchiolar collagen deposition. Comparative histopathologic analysis demonstrated that sustained club cell injury was sufficient to induce epithelial metaplasia, airway wall thickening, peribronchiolar infiltrates, and clusters of intraluminal airway macrophages that recapitulated key abnormalities observed in DRCB. Depletion of alveolar macrophages in mice decreased activation of transforming growth factor-β and ameliorated constrictive bronchiolitis. Collectively, these findings implicate sustained club cell injury in the development of DRCB and delineate pathways that may yield biomarkers and treatment targets for this disorder.


Expression of m6A Regulators Correlated With Immune Microenvironment Predicts Therapeutic Efficacy and Prognosis in Gliomas.
N6-methyladenosine (m6A) RNA methylation and tumor immune microenvironment played crucial roles in cancer development. However, their association in gliomas remains to be fully elucidated. A total of 2144 glioma patients from CGGA, TCGA, and Rembrandt databases were extracted in our study, in which 325 were set as the training cohort and 1819 were defined as the validation cohort. Survival differences evaluated by Kaplan-Meier analysis between groups. Patients were clustered into subgroups by consensus clustering. ESTIMATE algorithm was applied to calculate immune and stroma scores. The infiltration of immune cells was characterized by TIMER algorithm. The risk signature was constructed by multivariate Cox regression analysis. Nineteen m6A regulators were highly expressed in glioma tissues. The expression of m6A regulators was associated with prognoses, grade, isocitrate dehydrogenase (IDH) status, and 1p19q status of gliomas. Two subgroups were identified by consensus clustering, in which cluster 1 was associated with favorable prognosis, high stroma and immune scores, and high immune infiltration. When the patients were divided into high risk and low risk groups based on their risk scores, we found that patients in the high risk group had poor prognoses. Besides, patients in the high risk group had a higher stroma and immune scores, and higher abundance of immune infiltration. These results were further verified in the validation cohort, which contained three independent datasets. Moreover, patients in the low risk group enjoyed better prognoses without chemoradiotherapy or single chemotherapy. Our study revealed that m6A regulators could predict the prognosis and therapeutic efficacy, and were also associated with the immune microenvironment in gliomas.


Effect of Ketogenic Diet on Quality of Life in Adults with Chronic Disease: A Systematic Review of Randomized Controlled Trials.
Chronic diseases adversely affect quality of life (QOL). The ketogenic diet (KD) may improve the QOL. The aim of this systematic review was to summarize the available evidence of randomized controlled trials (RCTs) to establish the effect of KD on the QOL in adults with chronic diseases. Reporting followed PRISMA guidelines. We included randomized controlled trials (RCTs) conducted on adults with chronic disease including an intervention group that received KD and a control group, and where QOL was reported as outcome. We searched PubMed, APA PsycInfo, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Library, and Clinicaltrials.gov, and the references of the included articles and previous relevant reviews, without language or time restrictions. We critically appraised included studies and narratively synthesized their findings. Nine RCTs were included. The risk of bias was low, except of allocation concealment and blinding. In patients with cancer: one RCT found an improvement in overall QOL, another reported improved physical component summary, and one found no superiority of KD in all QOL domains. In patients with neurological disorders: improved QOL was reported in Alzheimer's disease patients, whereas no difference in mental and physical health QOL was noted in patients with multiple sclerosis. In patients with obesity and type II diabetes: one RCT reported superiority of energy-restricted KD in improving role functioning, mental health, health perceptions, and pain compared with guideline-based diet, whereas in another RCT, high and low carbohydrate diets achieved comparable improvements. Among patients with knee osteoarthritis, no differences between KD and low-fat groups were noted. Dietary compliance with the KD, reported in three studies, was shown to be high. Side effects were mostly noted during the first weeks of intervention, and adverse events were not markedly different with KD and the comparison diet. The evidence from RCTs investigating the effect of KD on QOL in adults with chronic disease is inconclusive. The promising effect noted in some included studies and the low rates of adverse events and side effects encourage future investigations in this regard.


Ixora coccinea Linn.: traditional uses, phytochemistry and pharmacology.
Ixora coccinea Linn., (Rubiaceae) commonly known as jungle of geranium and red ixora, is an evergreen shrub found throughout India. Depending on the medical condition, the flowers, leaves, roots, and the stem are used to treat various ailments in the Indian traditional system of medicine, the Ayurveda, and also in various folk medicines. The fruits, when fully ripe, are used as a dietary source. Phytochemical studies indicate that the plant contains important phytochemicals such as lupeol, ursolic acid, oleanolic acid, sitosterol, rutin, lecocyanadin, anthocyanins, proanthocyanidins, glycosides of kaempferol and quercetin. Pharmacological studies suggest that the plant possesses antioxidative, antibacterial, gastroprotective, hepatoprotective, antidiarrhoeal, antinociceptive, antimutagenic, antineoplastic and chemopreventive effects, thus lending scientific support to the plant's ethnomedicinal uses. In the present review, efforts are made in addressing its ethnomedicinal uses, chemical constituents, and validated pharmacological observations.


Stability and instability in alcohol diagnosis from ages 18 to 21 and ages 21 to 25 years.
Only in recent years have longitudinal studies of adolescents diagnosed alcohol use disorders and these have not distinguished between abuse and dependence. This study describes the course of disorder from age 18 to age 25 for abuse and dependence and investigates the extent to which continuities in disorder can be explained by background factors. A birth cohort of 1,265 individuals from Christchurch, New Zealand, followed annually to age 16 years then at 18, 21 and 25 years (1,003 at age 25). DSM-IV diagnoses were made from reports of alcohol symptoms at 18, 21 and 25 years. The most stable diagnosis was that of no diagnosis, with 83-91% staying the same from one interview to the next. There were high rates of remission to no disorder; 57-75% for those with initial abuse and 50-54% of those with initial dependence. Nonetheless prior diagnosis was a strong predictor of subsequent diagnosis (ORs of 3.7-27.6). Adjustment for background risk factors reduced these odds ratios but all remained significant and substantial (minimum 2.6). The dual finding of substantial discontinuity and substantial continuity indicates that both public health and treatment interventions are warranted.


Effects of acute sodium omission on insulin release, ionic flux and membrane potential in mouse pancreatic B-cells.
The effects of acute omission of extracellular Na+ on pancreatic B-cell function were studied in mouse islets, using choline and lithium salts as impermeant and permeant substitutes, respectively. In the absence of glucose, choline substitution for Na+ hyperpolarized the B-cell membrane, inhibited 86Rb+ and 45Ca2+ efflux, but did not affect insulin release. In contrast, Li+ substitution for Na+ depolarized the B-cell membrane and caused a Ca2+-independent, transient acceleration of 45Ca2+ efflux and insulin release. Na+ replacement by choline in the presence of 10 mM glucose and 2.5 mM Ca2+ again rapidly hyperpolarized the B-cell membrane. This hyperpolarization was then followed by a phase of depolarization with continuous spike activity, before long slow waves of the membrane potential resumed. Under these conditions, 86Rb+ efflux first decreased before accelerating, concomitantly with marked and parallel increases in 45Ca2+ efflux and insulin release. In the absence of Ca2+, 45Ca2+ and 86Rb+ efflux were inhibited and insulin release was unaffected by choline substitution for Na+. Na+ replacement by Li+ in the presence of 10 mM glucose rapidly depolarized the B-cell membrane, caused an intense continuous spike activity, and accelerated 45Ca2+ efflux, 86Rb+ efflux and insulin release. In the absence of extracellular Ca2+, Li+ still caused a rapid but transient increase in 45Ca2+ and 86Rb+ efflux and in insulin release. Although not indispensable for insulin release, Na+ plays an important regulatory role in stimulus-secretion coupling by modulating, among others, membrane potential and ionic fluxes in B-cells.


Electrocatalytic determination of nitrite based on straw cellulose/molybdenum sulfide nanocomposite.
Cellulose is the most abundant, renewable, biodegradable natural polymer resource on earth, which can be a good substrate for catalysis. In this work, straw cellulose has been oxidized through 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-mediated oxidation, and then a TEMPO oxidized straw cellulose/molybdenum sulfide (TOSC-MoS2) composite has been synthesized via a hydrothermal method. Fourier transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) analysis confirm that TOSC and MoS2 have successfully composited. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images show the TOSC as a carbon nanotube-like structure and edged MoS2 grows on the TOSC substrate. The TOSC-MoS2 modified glassy carbon electrode (GCE) is used as a simple and non-enzymatic electrochemical sensor. Cyclic Voltammetry (CV) result shows TOSC-MoS2 has excellent electrocatalytic activity for the oxidation of nitrite. The amperometric response result indicates the TOSC-MoS2 modified GCE can be used to determine nitrite concentration in wide linear ranges of 6.0-3140 and 3140-4200µM with a detection limit of 2.0µM. The proposed sensor has good anti-interference property. Real sample analysis and the electrocatalytic mechanism have also been presented.


Loop region-specific oligonucleotide probes for loop-mediated isothermal amplification-enzyme-linked immunosorbent assay truly minimize the instrument needed for detection process.
Enteric fever represents a significant public health burden in less-developed countries. Therefore, there is a great need for developing an improved diagnostic tool adapted to the demands of poor-resource clinical laboratories in those countries. The current study has developed a reliable loop-mediated isothermal amplification (LAMP)-enzyme-linked immunosorbent assay (ELISA) for diagnosis of enteric fever with a minimal equipment dependency. The LAMP-ELISA assay involves direct incorporation of a labeled nucleotide into amplicons during the amplification of the SPA3440 gene, their hybridization to the unique tagged oligonucleotide probes during the LAMP reaction, and finally detection of labeled LAMP amplicons by immunoassay technology. Because the designed oligonucleotide probes target the single-stranded DNA segment within the LAMP amplicons, the probe hybridization stage is performed simultaneously with the amplification process. This novel probe design strategy allows both the amplification and hybridization stages to be performed simultaneously and isothermally in a water bath. Among the bacteria tested, positive results were observed only with enteric fever causative bacteria. The LAMP-ELISA assay was successfully applied to artificially contaminated blood samples with a detection limit of 10 colony-forming units (CFU)/ml, which was 100 times more sensitive than polymerase chain reaction (PCR) and turbidity assessment-based conventional LAMP methods. The new assay is considered to be an effective method for diagnosis of enteric fever.