Cyclooxygenase inhibitors: drugs for cancer prevention.
Evidence that chronic intake of non-steroidal anti-inflammatory drugs, especially aspirin, prevents cancer development continues to accumulate. The data are particularly convincing for colorectal cancer; however, because of well-known side effects, they cannot routinely be recommended for this purpose. An appreciation of the mechanisms that underlie their anti-cancer effects might permit the development of safer agents. Intensive investigation has led to the characterization of several potential chemopreventive mechanisms of action of these drugs. Antineoplastic actions could result from effects on overlapping processes in the different cell-types that comprise tumors, such as epithelial and stromal cells.


Bioactive glass fillers reduce bacterial penetration into marginal gaps for composite restorations.
Bioactive glass (BAG) is known to possess antimicrobial and remineralizing properties; however, the use of BAG as a filler for resin based composite restorations to slow recurrent caries has not been studied. Accordingly, the objective of this study was to investigate the effect of adding 15wt% BAG to a resin composite on bacterial biofilms penetrating into marginal gaps of simulated tooth fillings in vitro during cyclic mechanical loading. Human molars were machined into approximately 3mm thick disks of dentin and 1.5-2mm deep composite restorations were placed. A narrow 15-20 micrometer wide dentin-composite gap was allowed to form along half of the margin by not applying dental adhesive to that region. Two different 72wt% filled composites were used, one with 15wt% BAG filler (15BAG) and the balance silanated strontium glass and one filled with aerosol silica and silanated strontium glass without BAG (0BAG-control). Samples of both groups had Streptococcus mutans biofilms grown on the surface and were tested inside a bioreactor for two weeks while subjected to periods of cyclic mechanical loading. After post-test biofilm viability was confirmed, each specimen was fixed in glutaraldehyde, gram positive stained, mounted in resin and cross-sectioned to reveal the gap profile. Depth of biofilm penetration for 0BAG and 15BAG was quantified as the fraction of gap depth. The data were compared using a Student's t-test. The average depth of bacterial penetration into the marginal gap for the 15BAG samples was significantly smaller (∼61%) in comparison to 0BAG, where 100% penetration was observed for all samples with the biofilm penetrating underneath of the restoration in some cases. BAG containing resin dental composites reduce biofilm penetration into marginal gaps of simulated tooth restorations. This suggests BAG containing composites may have the potential to slow the development and propagation of secondary tooth decay at restoration margins.


Parental social coaching promotes adolescent peer acceptance across the middle school transition.
The present study investigated longitudinal associations between behavioral and cognitive dimensions of parental social coaching (i.e., advice about how to behave or think about peer challenges) and young adolescents' peer acceptance, and whether such associations are moderated by youths' social skills. Time 1 (T1) participants included 123 young adolescents (M age = 12.03 years; 50% boys; 58.5% European American). Parents gave open-ended reports about their social coaching to hypothetical peer stress scenarios, which were coded from low to high quality on behavioral and cognitive dimensions. Parents and teachers reported on adolescent prosocial behavior (i.e., social-behavioral skills), and adolescents reported on their social appraisals and social self-efficacy (i.e., social-cognitive skills). At T1 (before the first year of middle school) and Time 2 (approximately 10 months later, after the first year of middle school), parents and teachers rated adolescent peer acceptance. Analyses revealed that parents' prosocial behavioral advice and benign cognitive framing independently predicted adolescents' higher peer acceptance prospectively (controlling for earlier levels of peer acceptance). Furthermore, adolescent social skills moderated links between coaching and peer acceptance. Specifically, adolescents with higher, but not lower, social-cognitive skills became more accepted in the context of higher-quality coaching, supporting a "capitalization" pattern, such that these youth may be better able to utilize coaching suggestions. Results underscore the utility of parents' behavioral advice and cognitive framing for adolescent peer adjustment across the middle school transition and suggest that optimal social-coaching strategies may depend in part on adolescent social skill level. (PsycINFO Database Record


Autoradiographic studies of the diurnal rhythm of the cell proliferation in the adrenal cortex of the rat.
With the aid of the autoradiographic technique we examined the question of diurnal or circadian rhythm of the cell proliferation as well as the mitotic rate in the three zones of the adrenal cortex of the rat. To evaluate the diurnal rhythm it is necessary to run experiments within 24-hour intervals. In order to examine observed variations as to their reproducibility we prolonged our investigations over a period of 72 hours. The proliferation activity as well as the mitotic rate in the zona glomerulosa show no diurnal rhythm. This is not so in the zona fasciculata. Here we find a correlated circadian rhythm for both parameters.


Cherubism: a rare case report with literature review.
Cherubism is an autosomal dominant disorder caused by a mutation of the gene encoding the binding protein SH3BP2. However, non-hereditary forms are observed, probably related to a de novo mutation. It is clinically manifested by an enlargement or a deformation of the jaw associated with a malposition of the teeth. In severe forms, these deformations can have a psychological impact, associated with ocular complications, as well as a reduction of the pharynx lumen and phonation disorders. The appearance of the lesions on imaging is not very specific, however it remains essential for the mapping of the lesions. We report a case of cherubism in a 12-year-old boy with no family history. This case report's objective is to identify the radiological aspect of this pathology and establish an early diagnosis to oriented therapeutic interventions.


Realist evaluations in low- and middle-income countries: reflections and recommendations from the experiences of a foreign researcher.
Realist evaluation, a methodology for exploring generative causation within complex health interventions to understand 'how, why and for whom' programmes work, is experiencing a surge of interest. Trends indicate that the proliferation in the use of this methodology also applies to research in low- and middle-income countries (LMICs). The value of using realist evaluation for project evaluation is also being noticed by non-governmental organisations (NGOs) and other programme implementers within such contexts. Yet, there is limited exploration of the use of realist evaluations in LMICs, especially their use by foreign researchers. This paper draws on the author's experience of conducting two realist evaluations across three different sub-Saharan African settings: Mundemu, Tanzania; Kabale, Uganda and Marsabit, Kenya. The realist evaluations were used as an operations research methodology to study two NGO community health programmes. This paper highlights four main challenges experienced by the author throughout the methodological process: (1) power imbalances prevalent during realist interviews, (2) working through translation and what this means for identfying Context-Mechanism-Outcome Configurations, (3) limited contextual familiarity and being an 'engaged researcher' and (4) the use or dependence on 'WEIRD' theories (i.e. theories based on the study of Western, Educated, Industrialized, Rich, Democratic people) within testing and refinement. Realist evaluation's enticing and straightforward slogan of finding 'what works, for whom and why' is in contrast to the complexity of the methodology used to generate these results (and often to the results themselves). Striking a balance between theory and pragmatism, while adhering to realist ontological underpinnings of generative causation and retroduction, is no easy task. This paper concludes by providing concrete recommendations for those who want to undertake a realist evaluation, with particular attention to cross-cultural settings, in light of the aforementioned challenges. In doing so, it aims to foster improved methodological rigour and help those engaging in this research methodology to work towards more appropriate and contextually relevant findings.


A new canestriniid mite, Bircericola bertrami n. g., n. sp. (Acari: Astigmata: Canestriniidae), parasitic on tenebrioniid beetles (Coleoptera: Tenebrionidae) from Tunisia.
The new genus Bircericola (Acari: Astigmata: Canestriniidae) and new species Bircericola bertrami from undetermined tenebrioniid beetles from Tunisia are described. Diagnostic features include: dorsal integument covered by longitudinal lines; suture separating propodosoma from hysterosoma present; male adanal suckers well developed; two pairs of paranal setae in males and six pairs in females; tarsi I-II very short (< 30 microm); and solenidia delta I and delta II subequal in length to setae cG I and cG II, respectively.


Vascular endothelial growth factor gene polymorphisms in spontaneously aborted fetuses.
The VEGF-1154G>A polymorphism has been reported to be a genetic risk factor for recurrent spontaneous abortion in various studies; however, these studies have focused on genetic analyses of pregnant women rather than aborted fetuses. To evaluate and confirm the association between the VEGF-1154G>A polymorphism and spontaneous abortion, we focused on the relationship between four polymorphisms in the VEGF gene (-2578C>A, -1154G>A, -634G>C, and 936C>T) and spontaneously aborted fetuses (SAFs). The subjects included 118 SAFs at <20 weeks gestation and 380 normal controls consisting of children and adults. The polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. Spontaneously aborted fetuses exhibited significantly different frequencies of the -2578CA+AA/-634CC and -1154GA+AA/-634CC combined genotypes compared with control subjects. The frequency of the -2578A/-1154A/-634C/936C haplotype was significantly higher in SAFs. VEGF genes -2578CA+AA/-634CC and -1154GA+AA/-634CC in the fetus are possible risk factors for spontaneous abortion.


PCSK9 Inhibition and Risk of Diabetes: Should We Worry?
Since the clinical benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors occurs in a setting of reducing low-density lipoprotein-cholesterol (LDL-C) to unprecedentedly low levels, it becomes of interest to investigate possible adverse effects pertaining to the risk of new-onset diabetes (NOD). While safety results reported in either meta-analyses or cardiovascular outcome trials FOURIER (with evolocumab) and ODYSSEY (with alirocumab) did not rise the incidence of NOD, Mendelian randomization analyses were almost concordant in showing an increased risk of NOD. This evidence was in line with post-marketing safety reports highlighting that evolocumab and alirocumab were primarily related to mild hyperglycaemia rather than diabetes, with most of the hyperglycaemic events occurring during the first 6 months of treatment. Considering the different nature of genetic studies and of randomized controlled trials, with careful monitoring of patients, particularly in the earlier phases of treatment, and the identification of those more susceptible to develop NOD, treatment with PCSK9 inhibitors should be of minimal concern.


Gastrointestinal secretory, motor and circulatory effects of corticotropin releasing factor (CRF).
This study was designed to determine the effects of CRF on the gastrointestinal functions such as secretion, motility and circulation in dogs. CRF was found to inhibit dose-dependently gastric acid response to pentagastrin but not to histamine. CRF stimulated pancreatic bicarbonate and protein secretion under basal conditions and in response to secretin or cholecystokinin (CCK). This stimulation was accompanied by an increase in plasma levels of pancreatic polypeptide (PP), but not of secretin or gastrin. CRF caused a partial inhibition of the migrating motor complexes in fasted dogs and increased spike activity of the small bowel. These motor effects of CRF probably resulted from the action of the released PP on the intestinal smooth muscle. CRF is also a potent and selective stimulant of the mesenteric blood flow. This effect may be secondary to the stimulation of intestinal motility and metabolism.


Sexually transmitted diseases in the tropics.
Several sexually transmitted diseases are endemic in the tropics. The morbidity and mortality from the human immunodeficiency viruses (HIV-1 and HIV-2) alone now rival that caused by Plasmodium falciparum malaria in several African and Asian nations. The genital ulcers of chancroid and syphilis facilitate the sexual transmission of HIV. Within the last two decades, the bacteria causing chancroid and gonorrhoea throughout the world have acquired plasmids that mediate bacterial resistance to penicillins and other antibiotics. This has significantly increased the costs of treatment. There is little prospect that the prevalence of gonorrhoea, chancroid, syphilis and HIV will decrease in the tropics in the near future without a global change in sexual behaviours and practices.


American Board of Emergency Medicine Longitudinal Study of Emergency Physicians.
The American Board of Emergency Medicine (ABEM) Longitudinal Study of Emergency Physicians (LSEP) was initiated to describe the development of a new medical specialty through the continuing study of the lives of representative emergency physicians. The study is designed to gather data periodically over many years to come. The primary purpose of this article is to provide a baseline for the information obtained and the methods used to develop the ABEM LSEP. Stratified, random sampling was used to select emergency physicians who represent different stages in the development of the specialty. Major data collections are conducted using a comprehensive questionnaire in 5-year intervals. Practice profiles were developed and analyzed. Homogeneous scales were created in 9 survey categories and analyzed. The survey was returned by 95% (958/1,008) of the emergency physicians. They are primarily middle-aged, family- and community-oriented, satisfied with their careers, and find that work stress is not a serious problem. Those who are trained in emergency medicine are the most likely to be involved in academic emergency medicine. The LSEP is a broad-reaching investigation of emergency physicians. Over time the study will describe (1) the individuals who move the specialty forward at different stages in the growth of the specialty, (2) the realities of practice in the specialty, (3) the relationship of the specialty to the personal lives and well-being of the specialty physicians, and (4) the changes seen in these factors over time.


Enhancement of microbial lipase activity via immobilization over sodium titanate nanotubes for fatty acid methyl esters production.
For cost effective fatty acid methyl esters (FAME) production, nanoparticles are used to make microbial lipase more stable and reusable. Sodium titanate nanotubes (TNT) were prepared by simple hydrothermal method for immobilization of different concentrations of lipase. All samples were characterized by XRD, FTIR and HRTEM. Samples of different concentrations of immobilized lipase on titanate nanotubes (TNT-L) were tested for FAME production against free lipase & pure TNT at 40 °C for 90 min. It was found that TNT-L achieved high conversion percentages even at low immobilized lipase concentrations, compared to free lipase. Immobilized lipase on TNT demonstrated enhanced recycling stability for 10 consecutive cycles, suggesting its use for FAME production.


Derivatization of N-methyl and cyclic amino acids with dimethylformamide dimethyl acetal.
Six amino acids containing either an N-methyl or a cyclic secondary amine were converted to volatile derivatives by reaction with dimethylformamide dimethyl acetal. The amine functionalities were formylated by way of an amide acetal intermediate while the carboxylic acid groups were esterified directly. The resulting N-formyl esters were stable to solvent extraction and exhibited gas chromatography-mass spectrometry properties suitable for assay development.


Changes of fluorescence and xanthophyll pigments during dehydration in the resurrection plantSelaginella lepidophylla in low and medium light intensities.
The changes in photosynthetic efficiency and photosynthetic pigments during dehydration of the resurrection plantSelaginella lepidophylla (from the Chiuhahuan desert, S.W. Texas, USA) were examined under different light conditions. Changes in the photosynthetic efficiency were deduced from chlorophyll a fluorescence measurements (Fo, Fm, and Fv) and pigment changes were measured by HPLC analysis. A small decrease in Fv/Fm was seen in hydrated stems in high light (650 μmol photons·m-2·s-1) but not in low light (50 μmol photons·m-2·s-1). However, a pronounced decline in Fv/Fm was observed during dehydration in both light treatments, after one to two hours of dehydration. A rise in Fo was observed only after six to ten hours of dehydration. Concomitant with the decrease in photosynthetic efficiency during dehydration a rise in the xanthophyll zeaxanthin was observed, even in low-light treatments. The increase in zeaxanthin can be related to previously observed photoprotective non-photochemical quenching of fluorescence in dehydrating stems ofS. lepidophylla. We hypothesize that under dehydrating conditions even low light levels become excessive and zeaxanthin-related photoprotection is engaged. We speculate that these processes, as well as stem curling and self shading (Eickmeier et al. 1992), serve to minimize photoinhibitory damage toS. lepidophylla during the process of dehydration.


Drug use in a small midwestern community and relationships to selected characteristics.
A description of 1074 high school students' alcohol and other drug (AOD) use along with the consequences of such use was supplemented with comparisons of grade level and gender differences and analyses of the relationships between AOD use and incidence of adverse consequences with grade point average, attendance at religious services, frequency of dating, frequency of driving a car and frequency of having trouble at school. Alcohol was clearly the drug of choice and produced a variety of adverse consequences. Most frequently reported were arguments, trouble with parents and at school and nausea or vomiting. Grade level differences were found, but few significant gender differences emerged. Significant relationships between AOD use and consequences with all other independent variables were found.


Relative bioavailability to laying hens of indicator polychlorobiphenyls present in soil.
Transfer of indicator polychlorobiphenyls (PCBs) from soil into hen eggs may occur in hens reared outdoor, which ingest significant amounts of soil. This transfer depends on the bioavailability of the ingested compounds. The impact of soil on the bioavailability of indicator PCBs was assessed by means by a relative bioavailability (RBA) trial, in which their deposition in egg yolk and in abdominal fat, in response to their ingestion through contaminated-soil and through spiked-oil were compared. A sandy soil (709 μg indicator PCBs kg(-1) dry matter) was collected in the vicinity of a former fire involving treated wood. Twenty-eight laying hens were individually housed and fed one of the seven experimental diets during 14 d. The seven experimental diets were an uncontaminated control diet, three diets in which contaminated soil was introduced at levels of 3%, 6% and 9% and three diets in which spiked oil was introduced to achieve similar levels and profile of contaminants. Yolk, abdominal fat and liver were collected at the end of exposure. Indicator PCBs were extracted by ASE (Accelerated Solvent Extraction) and analyzed by GC-HMRS. Within each ingested matrix, the concentration of indicator PCBs in yolk and in abdominal fat linearly increased with the amount of indicator PCB ingested (P<0.001). Except for PCB 28, the slopes of the responses to soil and to oil could not be differentiated (P>0.1). RBA estimates did not differ from 1 for all indicator PCBs except for PCB 28, for which it was 0.58-0.59. Measurements performed on liver confirm these conclusions.


The association of endothelial nitric oxide synthase (eNOS) G894T gene polymorphism with responsiveness to a selective α1 -blocker in men with benign prostatic hyperplasia related lower urinary tract symptoms.
To prospectively investigate the association of endothelial nitric oxide synthase (eNOS) G894T gene polymorphism with responsiveness to a selective α1 -blocker in men with benign prostatic hyperplasia related lower urinary tract symptoms (BPH/LUTS), as nitric oxide has recently gained increasing recognition as an important neurotransmitter of functions in the lower urinary tract. In all, 136 men with BPH/LUTS were recruited from urology outpatient clinics in a university hospital. Oral therapy with doxazosin gastrointestinal therapeutic system (GITS) 4 mg once-daily was given for 12 weeks. The drug efficacy was assessed by the changes from baseline in the total International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax ) and post-void residual urine volume (PVR) at 12 weeks of treatment. The 'responders' to doxazosin GITS were defined as those who had a total IPSS decrease of >4 points from baseline. eNOS G894T polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism method. Patients had statistically significant improvements in total IPSS, quality of life score, and Qmax (P < 0.01) after a 12-week period of treatment. Using multiple logistic regression analysis adjusted for age and IPSS, our results showed that being a eNOS 894T allele carrier was an independent risk factor for being a drug non-responder (P = 0.03, odds ratio 4.19). Moreover, a decreased responder rate (P = 0.01), as well as the lower improvements in IPSS (P = 0.02) and Qmax (P = 0.03) were significantly associated with increment in the T allele number. The presence of the eNOS 894T allele had a significantly negative impact on responsiveness to a selective α1 -blocker in BPH/LUTS treatment, suggesting that eNOS G894T gene polymorphism may be a genetic susceptibility factor for α1 -blocker efficacy in men with BPH/LUTS.


Fatty acid synthesis is a target for antibacterial activity of unsaturated fatty acids.
Long-chain unsaturated fatty acids, such as linoleic acid, show antibacterial activity and are the key ingredients of antimicrobial food additives and some antibacterial herbs. However, the precise mechanism for this antimicrobial activity remains unclear. We found that linoleic acid inhibited bacterial enoyl-acyl carrier protein reductase (FabI), an essential component of bacterial fatty acid synthesis, which has served as a promising target for antibacterial drugs. Additional unsaturated fatty acids including palmitoleic acid, oleic acid, linolenic acid, and arachidonic acid also exhibited the inhibition of FabI. However, neither the saturated form (stearic acid) nor the methyl ester of linoleic acid inhibited FabI. These FabI-inhibitory activities of various fatty acids and their derivatives very well correlated with the inhibition of fatty acid biosynthesis using [(14)C] acetate incorporation assay, and importantly, also correlated with antibacterial activity. Furthermore, the supplementation with exogenous fatty acids reversed the antibacterial effect of linoleic acid, which showing that it target fatty acid synthesis. Our data demonstrate for the first time that the antibacterial action of unsaturated fatty acids is mediated by the inhibition of fatty acid synthesis.


Peritoneal lymphoma with ascites mimicking portal hypertensive ascites: A case report.
Lymphoma with an initial manifestation of ascites and peritoneal invasion is rare. A 65-year-old woman presented to the emergency department with a 3-week history of abdominal distention, anorexia, and night sweating, and a 2-week history of melena. She was a silent hepatitis B virus carrier. Abdominal ultrasound showed massive ascites without cirrhosis. Abdominal computed tomography revealed ascites, infiltrative peritoneal lesions with omental cake appearance, and lymphadenopathies. We performed paracentesis and the ascites cytology was obtained. The patient also underwent esophagogastroduodenoscopy, which showed ulcerative tumors in the stomach. Both ascites cytology and pathology of the gastric tumors confirmed the diagnosis of B-cell lymphoma. This patient received 7 cycles of chemotherapy. Follow-up imaging studies revealed partial remission of lymphoma, but an enlargement of residual tumors in omentum and mesentery, which resulted in intractable ascites and rapid deterioration of performance status. Despite a change of regimen of chemotherapy, this patient expired 10 months after diagnosis. Lymphoma should be one of the differential diagnoses in patients with intractable ascites not attributable to other comorbidities.


Urinary porphyrins as biological indicators of oxidative stress in the kidney. Interaction of mercury and cephaloridine.
Reduced porphyrins (hexahydroporphyrins, porphyrinogens) are readily oxidized in vitro by free radicals which are known to mediate oxidative stress in tissue cells. To determine if increased urinary porphyrin concentrations may reflect oxidative stress to the kidney in vivo, we measured the urinary porphyrin content of rats treated with mercury as methyl mercury hydroxide (MMH) or cephaloridine, both nephrotoxic, oxidative stress-inducing agents. Rats exposed to MMH at 5 ppm in the drinking water for 4 weeks showed a 4-fold increase in 24-hr total urinary porphyrin content and a 1.3-fold increase in urinary malondialdehyde (MDA), an established measure of oxidative stress in vivo. Treatment with cephaloridine alone (10-500 mg/kg, i.p.) produced a dose-related increase in urinary MDA and total porphyrin levels up to 1.6 and 7 times control values, respectively. Injection of MMH-treated rats with cephaloridine (500 mg/kg) caused a synergistic (20-fold) increase in urinary porphyrin levels, but an additive (1.9-fold) increase in the MDA concentration. Studies in vitro demonstrated that cephaloridine stimulated the iron-catalyzed H2O2-dependent oxidation of porphyrinogens to porphyrins in the absence of either microsomes or mitochondria. Additionally, porphyrinogens were oxidized to porphyrins in an iron-dependent microsomal lipid peroxidation system. Moreover, porphyrinogens served as an effective antioxidant (EC50 approximately 1-2 microM) to lipid peroxidation. These results demonstrate that MMH and cephaloridine synergistically, as well as individually, promote increased oxidation of reduced porphyrins in the kidney and that this action may be mechanistically linked to oxidative stress elicited by these chemicals. Increased urinary porphyrin levels may, therefore, represent a sensitive indicator of oxidative stress in the kidney in vivo.


Human dental pulp stem cells derived from cryopreserved dental pulp tissues of vital extracted teeth with disease demonstrate hepatic-like differentiation.
Reviewing the literature, hepatic differentiation of human dental pulp stem cells (hDPSCs) from cryopreserved dental pulp tissues of vital extracted teeth with disease has not been studied. This study is aimed to evaluate the hypothesis that hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease could possess potential hepatic differentiation. Forty vital extracted teeth with disease recruited for hDPSCs isolation, stem cell characterization and hepatic differentiation were randomly and equally divided into group A (liquid nitrogen-stored dental pulp tissues) and group B (freshly derived dental pulp tissues). Samples of hDPSCs isolated from groups A and B but without hepatic growth factors formed negative controls. A well-differentiated hepatocellular carcinoma cell line was employed as a positive control. All the isolated hDPSCs from groups A and B showed hepatic-like differentiation with morphological change from a spindle-shaped to a polygonal shape and normal karyotype. Differentiated hDPSCs and the positive control expressed hepatic metabolic function genes and liver-specific genes. Glycogen storage of differentiated hDPSCs was noted from day 7 of differentiation-medium culture. Positive immunofluorescence staining of low-density lipoprotein and albumin was observed from day 14 of differentiation-medium culture; urea production in the medium was noted from week 6. No hepatic differentiation was observed for any of the samples of the negative controls. We not only demonstrated the feasibility of hepatic-like differentiation of hDPSCs from cryopreserved dental pulp tissues of vital extracted teeth with disease but also indicated that the differentiated cells possessed normal karyotype and were functionally close to normal hepatic-like cells. Copyright © 2013 John Wiley & Sons, Ltd.


Malignant cells can be sensitized to undergo growth inhibition and apoptosis by arsenic trioxide through modulation of the glutathione redox system.
Arsenic trioxide (As2O3) induces clinical remission in acute promyelocytic leukemia (APL) with minimal toxicity and apoptosis in APL-derived NB4 cells at low (1 to 2 micromol/L) concentration. We examined the basis for NB4 cell sensitivity to As2O3 to identify experimental conditions that would render other malignant cells responsive to low concentrations of As2O3. The intracellular glutathione (GSH) content had a decisive effect on As2O3-induced apoptosis. Highly sensitive NB4 cells had the lowest GSH and the sensitivity of other cell lines was inversely proportional to their GSH content. The t(14;18) B-cell lymphoma cell line had low GSH levels and sensitivity to As2O3 at levels slightly higher than in APL cells. Experimental upmodulation of GSH content decreased the sensitivity to As2O3. Ascorbic acid and buthionine sulfoxide (BSO) decreased GSH to a greater extent, and rendered malignant cells more sensitive to As2O3. As2O3-induced apoptosis was not enhanced by ascorbic acid in normal cells, suggesting that the combination of ascorbic acid and As2O3 may be selectively toxic to some malignant cells. Ascorbic acid enhanced the antilymphoma effect of As2O3 in vivo without additional toxicity. Thus, As2O3 alone or administered with ascorbic acid may provide a novel therapy for lymphoma.


Comparative studies with Fluosol, Dextran, their mixture, or autologous blood in experimental hypovolemic shock.
In 42 rabbits blood pressure was held at 40 mmHg/15 min. Various treatments resulted in equal recovery from shock in 4 groups. There is, however, some evidence that: (1) Dextran 40 was superior regarding microcirculation; (2) Fluosol added more oxygen to the tissues; and (3) a combined treatment showed both effects.


Evaluation of genotoxic effects of sodium propionate, calcium propionate and potassium propionate on the root meristem cells of Allium cepa.
The effects of different treatments with food preservatives, sodium propionate (SP), calcium propionate (CP) and potassium propionate (PP), on the cytology and DNA content of Allium cepa were investigated. Five concentrations of these additives - 1000, 1500, 2000, 2500, and 3000ppm - were applied for 24, 48, and 72h. All concentrations of these chemicals showed an inhibitory effect on cell division in root-tips of A. cepa and caused a decrease in mitotic index values. Additionally, all treatments changed the frequency of mitotic phases when compared with the control groups. These compounds increased chromosome abnormalities in test material. Among these abnormalities were C-mitosis, anaphase bridges, micronuclei, binucleated cells, stickiness, laggards, and chromosome breaks. The nuclear DNA contents decreased when compared with control groups.


Mycobacterium abscessus and massiliense lung infection during macrolide treatment for bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation.
In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT), post-transplant lung infection is critical for their prognosis. Mycobacterium abscessus complex is not fully recognized as a nontuberculous mycobacteria (NTM) pathogen of post-SCT lung infection. Here, we present three post-allogeneic SCT patients who developed pulmonary infection caused by M. abscessus complex including M. abscessus and M. massiliense. In all three cases, macrolide antibiotics had been administered for bronchiolitis obliterans syndrome (BOS) before the confirmation of their infection, and macrolide resistance was noted in the M. abscessus isolates, one of which resulted in an unfavorable treatment outcome. It is important to consider M. abscessus lung infection as well as other NTM in patients receiving allo-SCT, particularly those receiving macrolide therapy for BOS.


Peripherally inserted central catheter using the saphenous vein: importance of two-view radiographs to determine the tip location.
Two cases are described in which a peripherally inserted central catheter tip in the saphenous vein appeared to be in the inferior vena cava by an anteroposterior abdominal radiograph, but a lateral view revealed the catheter tip to be outside the inferior vena cava. The actual location of the catheter tip placement may be misleading with a single radiograph. Two-view radiographs should be considered to assure the proper catheter tip placement.


Bayesian adaptive method for estimating speed-accuracy tradeoff functions of multiple task conditions.
The speed-accuracy tradeoff (SAT) often makes psychophysical data difficult to interpret. Accordingly, the SAT experimental procedure and model were proposed for an integrated account of the speed and accuracy of responses. However, the extensive data collection for a SAT experiment has blocked its popularity. For a quick estimation of SAT function (SATf), we previously developed a Bayesian adaptive SAT method, including an online stimulus selection strategy. By simulations, the method was proved efficient with high accuracy and precision with minimal trials, adequate for practically applying a single condition task. However, it calls for extensions to more general designs with multiple conditions and should be revised to achieve improved estimation performance. It also demands real experimental validation with human participants. In the current study, we suggested an improved method to measure SATfs for multiple task conditions concurrently and to enhance robustness in general designs. The performance was evaluated with simulation studies and a psychophysical experiment using a flanker task. Simulation results revealed that the proposed method with the adaptive stimulus selection strategy efficiently estimated multiple SATfs and improved performance even for cases with an extreme parameter value. In the psychophysical experiment, SATfs estimated by minimal adaptive trials (1/8 of conventional trials) showed high agreement with those by conventional trials required for reliably estimating multiple SATfs. These results indicate that the Bayesian adaptive SAT method is reliable and efficient in estimating SATfs in most experimental settings and may apply to SATf estimation in general behavioral research designs.


Exploring gender differences in body image, eating pathology, and sexual harassment.
This study examines the relationship between body image (weight/shape concerns), eating pathology, and sexual harassment among men and women (N=2446). Hierarchical regressions controlling for depression revealed main effects of gender such that women reported greater weight/shape concerns, eating pathology, dietary restraint, eating concerns, and binge eating compared to men. Main effects for sexual harassment indicated that as harassment increased, participants reported increased weight/shape concerns, eating pathology, dietary restraint, eating concerns, binge eating, and compensatory behaviors. There were small but significant interactions between gender and harassment for eating pathology total score (which included each of the domains listed above), weight/shape concerns, dietary restraint, and eating concerns such that the relationship between increased harassment and increased pathology was stronger for women compared to men. The largest interaction was found for compensatory behaviors, such that while women and men's scores both increased as harassment increased, the relationship was stronger for men.


Structure, cell-specific expression, and mating-induced regulation of a Drosophila melanogaster male accessory gland gene.
The accessory gland of male insects is a secretory tissue of the genital tract made up of several distinct cell types. It secretes components of the ejaculatory fluid which have an important effect on the postmating behavior of the female. We have examined the sequence, structure, and expression of a gene, mst 316, expressed exclusively in the accessory glands of male Drosophila melanogaster. The mst 316 RNA encodes a small, basic protein of 52 amino acids that exhibits features common to precursors of secreted peptides, including a hydrophobic N-terminus. The tissue-specific expression of the mst 316 gene was studied using an mst 316--lacZ hybrid gene inserted into Drosophila by germ line transformation. The mst 316-lacZ fusion protein is expressed exclusively in the "main" cells of the accessory gland. It is first detected upon eclosion and exhibits a burst of synthesis in the first 3 days of adult life. The synthesis of the fusion protein is stimulated by mating, so that beta-galactosidase activity levels are two- to sixfold higher in males allowed to copulate with females compared to virgin male controls of the same age. The mating-stimulated synthesis of the mst 316-lacZ fusion protein, and by inference of the native gene product, appears to be due at least in part to increased transcript levels.


Airborne fine particulate matter induces an upregulation of endothelin receptors on rat bronchi.
Airborne fine particulate matter (PM2.5) is a risk factor for respiratory diseases. However, little is known about the effects of PM2.5 on bronchi. The present study investigated the effect of airborne PM2.5 on rat bronchi and the underlying mechanisms. Isolated rat bronchial segments were cultured for 24 h. Endothelin (ET) receptor-mediated contractile responses were recorded using a wire myograph. The mRNA and protein expression levels of ET receptors were studied using quantitative real-time PCR, Western blotting, and immunohistochemistry. The results demonstrated that ETA and ETB receptor agonists induced remarkable contractile responses on fresh and cultured bronchial segments. PM2.5 (1.0 or 3.0 μg/ml) significantly enhanced ETA and ETB receptor-mediated contractile responses in bronchi with a markedly increased maximal contraction compared to the DMSO or fresh groups. PM2.5 increased the mRNA and protein expression levels of ETA and ETB receptors. U0126 (a MEK1/2 inhibitor) and SB203580 (a p38 inhibitor) significantly suppressed PM2.5-induced increases in ETB receptor-mediated contractile responses, mRNA and protein levels. SP600125 (a JNK inhibitor) and SB203580 significantly abrogated the PM2.5-induced enhancement of ETA receptor-mediated contraction and receptor expression. In conclusion, PM2.5 upregulates ET receptors in bronchi. ETB receptor upregulation is associated with MEK1/2 and p38 pathways, and the upregulation of ETA receptor is involved in JNK and p38 pathways.


The detection of Hammondia hammondi in Australia and the identification of a free-living intermediate host.
A cat fed commercially prepared cat food and free-living rats (Rattus rattus and R. norvegicus) passed coccidian oocysts which were morphologically similar to Toxoplasma gondii. Mice dosed with these oocysts did not develop toxoplasmosis, but instead developed small, thin-walled parasitic cysts containing small bradyzoites in their striated muscles. These cysts measured 35 to 90 micron by 9 to 40 micron and they resembled cysts of Hammondia hammondi. Unlike T. gondii this coccidian parasite was shown to have an obligatory two-host cycle and consequently it is considered to be H. hammondi. This represents the first recorded detection of H. hammondi in Australia. The source of the H. hammondi infection was a Rattus rattus. This represents the first record of a natural intermediate host for H. hammondi.


Fluorodeoxyglucose and methionine uptake in Lhermitte-Duclos disease: case report.
Lhermitte-Duclos disease (LDD) represents a focally indolent dysplastic growth of the cerebellar cortex. The 106 cases reported previously in the literature show an extremely slow evolution, and the operative indications and techniques for this disease entity are still controversial. The authors present the first case of LDD studied with positron emission tomography using the labeled tracers [(18)F]2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) and (11)C-labeled methionine ([(11)C]Met) to study the glucose and protein metabolism of the lesion. A 40-year-old woman suddenly became unconscious then completely recovered 5 minutes later. Magnetic resonance imaging of her brain showed a well-delineated 10 x 5-cm abnormal area with enlarged cerebellar folia, which led to the diagnosis of LDD. On positron emission tomographic scans, [(18)F]FDG and [(11)C]Met uptake in the normal cerebral and cerebellar cortex appeared higher than normal, reaching levels found in patients with primary malignant brain tumors. Moreover, the uptake of both tracers was heterogeneous, in contrast to the homogeneous uptake visualized on magnetic resonance imaging scans. The areas of greatest [(11)C]Met and [(18)F]FDG uptake were discordant. Some areas of greater than normal [(18)F]FDG uptake corresponded to areas of moderate or low [(11)C]Met uptake. Because of the important mass effect in the posterior fossa, total surgical resection was performed. A histological examination confirmed the diagnosis of LDD. This first reported metabolic study of LDD supports the view that LDD is an active and evolving disease. These data should prompt reevaluation of the indications for surgery in patients with this disease as well as the timing of surgery.


Medium-term outcome of posterior surgery in the treatment of non-tuberculous bacterial spinal infection.
to evaluate the outcome of posterior spinal stabilization surgery for the management of bacterial spinal infection. 21 patients with bacterial infection were managed surgically with posterior stabilization. Outcome measures included neurological status. Follow-up data collected using Spine Tango COMI questionnaires and Euro Qol EQ-5D. The mean improvement in neurological deficits was 0.91 Frankel grade. Residual symptoms of pain had no or minor effect on the work or usual activities in 52% of subjects, with 88% reported having either no or mid problems with mobility. Posterior surgery can improve neurological outcome in approximately half of the patients.


Improvement of Insomnia Symptoms following a Single 4-Hour CBT-I Workshop.
: Cognitive behavioral treatment for insomnia (CBT-I) is the first line of treatment for insomnia. However, the expanded use of CBT-I is limited by the number of specialty-trained clinicians in addition to the duration and cost of individual treatment sessions. One viable option is a single-session educational group format delivered by a trained health educator. : In a preliminary, single group pretest-posttest design, the effectiveness of group CBT-I delivered to community dwelling individuals with self-reported insomnia symptoms was evaluated. Participants completed the Insomnia Severity Index (ISI) and provided information on sleep aid use, prior to and 1-month post attendance of a single 4-hour CBT-I workshop. : Participants (N = 45) were 54 ± 16 years and 71% female. ISI scores significantly improved from baseline (20.09 ± 4.1) to 1-month follow-up (11.89 ±5.7; t = 10.1, p < .001) with an average change of 8.2 ± 5.4 points. Frequency of sleep aid use significantly dropped (χ2 = 105.7, p = .017). Eighty percent of participants reported sleeping better or much better at follow-up. Twenty percent of participants met criteria for remission of insomnia and 35.6% of participants had ISI change scores meeting criteria for a Minimally Important Difference associated with improvements in fatigue, work productivity, and health related quality of life. : These preliminary data suggest that a single 4-hour CBT-I workshop delivered by a health educator can significantly improve insomnia symptoms, improve subjective sleep quality, and reduce sleep aid use among community dwelling adults with and without co-morbidities within 1-month.


Three-Stage Nutrition Diagnosis for surgical patients at the perioperative period.
Medical nutrition therapy has been widely applied in various diseases as a fundamental or even a first-line treatment. Patient who undergoes a disease state especially at the perioperative period can be much improved with the help of nutrition therapy. Precise nutrition diagnosis should be conducted before applying any nutrition therapy. Traditional malnutrition diagnostic process, however, is a two-stage process (nutrition screening and nutrition assessment) which cannot precisely assess nutritional status of surgical patients or the consequences of being malnourished. This article systematically introduced a new nutrition diagnostic process - Three-Stage Diagnosis (nutrition screening, nutrition assessment, and comprehensive evaluation) and discussed its applications during perioperative period.


The fusion pore.
The secretory process requires many different steps and stages. Vesicles must be formed and transported to the target membrane. They must be tethered or docked at the appropriate sites and must be prepared for fusion (priming). As the last step, a fusion pore is formed and the contents are released. Release of neurotransmitter is an extremely rapid event leading to rise times of the postsynaptic response of less than 100 micro s. The release thus occurs during the initial formation of the exocytotic fusion pore. To understand the process of synaptic transmission, it is thus of outstanding importance to understand the molecular structure of the fusion pore, what are the properties of the initial fusion pore, how these properties affect the release process and what other factors may be limiting the kinetics of release. Here we review the techniques currently employed in fusion pore studies and discuss recent data and opinions on exocytotic fusion pore properties.


Survival of Escherichia coli O157:H7, Listeria monocytogenes 4b and Yersinia enterocolitica O3 in different yogurt and kefir combinations as prefermentation contaminant.
To compare microbiological safety of yogurt, kefir and different combinations of yogurt and kefir samples by using three foodborne pathogenic strains (Escherichia coli O157:H7, Listeria monocytogenes 4b and Yersinia enterocolitica O3) as indicators. Fresh yogurt and kefir drinks were added to pasteurized milk at a 5% rate either separately or together, and then incubated at different temperatures (43 degrees C for yogurt and 30 degrees C for kefir), depending on appropriate growth temperature of their starter microflora. While traditional yogurt was found to be the least suppressive on the three pathogenic micro-organisms, samples obtained from two subsequent fermentation process (samples fermented at 43 degrees C for 3 h and at 30 degrees C for 21 h) were more suppressive than that of traditional kefir. There was no significant survival difference between E. coli O157:H7 and L. monocytogenes 4b in samples tested (P > 0.05), but Y. enterocolitica O3 was more susceptible than other two test strains (P < 0.05). The microbiological safety of the dairy product fermented at two consecutive periods was superior than that of traditional yogurt or kefir alone. These experiments may mimic what happens when yogurt and kefir starter micro-organisms are combined in a milk fermentation process with different time and temperature periods.


IGF1 stabilizes sperm membrane proteins to reduce cryoinjury and maintain post-thaw sperm motility in buffalo (Bubalus bubalis) spermatozoa.
Insulin like growth factor 1 (IGF1) in the seminal plasma is reported to improve sperm motility by reducing oxidative stress. The present study was conducted to assess the effect of addition of IGF1 on sperm function and protein composition during cryopreservation process. Semen samples were collected from six Murrah buffaloes (2 ejaculates from each animal) and diluted (80 million/ml) in tris egg yolk extender and divided into control, T1, T2 and T3, groups supplemented with 0, 50, 100 and 150 ng of IGF1/mL, respectively. The semen was filled in straws (250 μL) and straws from each group were divided into two batches. One batch was processed for freezing and another batch was incubated at 4 °C for 4 h. The sperm kinematic and functional parameters were studied in both the batches. A significant (P < 0.05) positive effect of IGF1 was observed on functional membrane integrity (%) during incubation at 4 °C for 4 h in T3 as compared to control group. The spermatozoa (%) positive for structural membrane integrity, mitochondrial membrane potential and the metabolic activity in post-thaw semen were significantly (P < 0.05) high in T3 than the control group. The acrosomal integrity was significantly (P < 0.05) higher in T2 group as compared to control. The proteins (kDa) of 17.3 with pI 4.2 (calmodulin), 11.3 with pI 6.5 (dermcidin) and 18.1 with pI 5.5 (sperm acrosome membrane associated protein3) were protected in IGF1 group. The study suggests that IGF1 can be added to the extender for improving cryosurvial of buffalo spermatozoa.


Postoperative complications in the oldest old gastric cancer patients.
With the aging of the population, the number of elderly patients with gastric cancer is anticipated to increase. This study evaluated the feasibility of gastrectomy for patients over 85 years old. A total of 176 patients who underwent gastrectomy for gastric cancer were assigned into two groups: 75-84 years group (n = 152); and ≥85 years group (n = 24). Preoperative comorbidities, operative results, and postoperative outcomes were retrospectively analyzed. In terms of concurrent illness, no significant differences were observed between groups. Preoperative lymphocyte (Lym) count, hemoglobin (Hb) level and serum albumin (Alb) levels were significantly lower in the ≥85 years group than in the 75-84 years group (Lym: 11.0 ± 2.2 × 10²/mm³ vs. 14.9 ± 3.2 × 10²/mm³, P = 0.0009; Hb: 11.2 ± 2.3 mg/dl vs. 12.4 ± 1.5 mg/dl, P = 0.038; Alb: 3.5 ± 0.5 mg/dl vs. 4.1 ± 0.3 mg/dl, P = 0.0006, respectively). Percent vital capacity was likewise lower in the ≥85 years group than in the 75-84 years group (86.2 ± 11.4% vs. 96.1 ± 12.2%, P = 0.04). Percentage forced expiratory volume in 1 s showed no significant difference. Incidence of postoperative pneumonia was higher in the ≥85 years group than in the 75-84 years group (P = 0.006). Time to first flatus and postoperative hospital stay were similar in both groups. Patients over 85 years old are more likely to suffer postoperative pneumonia after gastrectomy than younger old patients. Preoperative risk assessment is essential for the oldest old patients.


Brainstem lesions are associated with sleep apnea in multiple sclerosis.
Studies linking MRI findings in MS patients with obstructive sleep apnea severity are limited. We conducted a retrospective study to assess MRI abnormalities associated with obstructive sleep apnea (OSA) in patients with multiple sclerosis (MS). We performed retrospective chart review of 65 patients with multiple sclerosis who had undergone polysomnography (PSG) for fatigue as well as brain MRI. We measured the number of lesions in the brainstem and calculated the standardized third ventricular width (sTVW) as a measure of brain atrophy, and subsequently performed correlation analyses of the apnea-hypopnea index (AHI) with brainstem lesion location, sTVW, and Expanded Disability Status Scale (EDSS). MS Patients with OSA were significantly older and had a higher body mass index (BMI) and higher AHI measures than patients without OSA. After adjustment for covariates, significant associations were found between AHI and lesion burden in the midbrain (p < 0.01) and pons (p = 0.05), but not medulla. Midbrain and pontine lesions burden correlated with AHI, suggesting MS lesion location could contribute to development of OSA.


20-HETE is associated with unfavorable outcomes in subarachnoid hemorrhage patients.
Emerging evidence has suggested that patients experiencing aneurysmal subarachnoid hemorrhage (aSAH) develop vascular dysregulation as a potential contributor to poor outcomes. Preclinical studies have implicated the novel microvascular constrictor, 20-hydroxyeicosatetraenoic acid (20-HETE) in aSAH pathogenesis, yet the translational relevance of 20-HETE in patients with aSAH is largely unknown. The goal of this research was to determine the relationship between 20-HETE cerebrospinal fluid (CSF) levels, gene variants in 20-HETE synthesis, and acute/long-term aSAH outcomes. In all, 363 adult patients (age 18 to 75) with aSAH were prospectively recruited from the University of Pittsburgh Medical Center neurovascular Intensive Care Unit. Patients were genotyped for polymorphic variants and cytochrome P450 (CYP)-eicosanoid CSF levels were measured over 14 days. Outcomes included delayed cerebral ischemia (DCI), clinical neurologic deterioration (CND), and modified Rankin Scores (MRS) at 3 and 12 months. Patients with CND and unfavorable 3-month MRS had 2.2- and 2.7-fold higher mean 20-HETE CSF levels, respectively. Patients in high/moderate 20-HETE trajectory groups (35.7%) were 2.5-, 2.1-, 3.1-, 3.3-, and 2.1-fold more likely to have unfavorable MRS at 3 months, unfavorable MRS at 12 months, mortality at 3 months, mortality at 12 months, and CND, respectively. These results showed that 20-HETE is associated with acute and long-term outcomes and suggest that 20-HETE may be a novel target in aSAH.


N-Containing Carbon-Coated β-Si3 N4 Enhances Si Anodes for High-Performance Li-Ion Batteries.
The lithiation/delithiation properties of α-Si3 N4 and β-Si3 N4 are compared and the carbon coating effects are examined. Then, β-Si3 N4 at various fractions is used as the secondary phase in a Si anode to modify the electrode properties. The incorporated β-Si3 N4 decreases the crystal size of Si and introduces a new NSiO species at the β-Si3 N4 /Si interface. The nitrogen from the milled β-Si3 N4 diffuses into the surface carbon coating during the carbonization heat treatment, forming pyrrolic nitrogen and CNO species. The synergistic effects of combining β-Si3 N4 and Si phases on the specific capacity are confirmed. The operando X-ray diffraction and X-ray photoelectron spectroscopy data indicate that β-Si3 N4 is partially consumed during lithiation to form a favorable Li3 N species at the electrode. However, the crystalline structure of the hexagonal β-Si3 N4 is preserved after prolonged cycling, which prevents electrode agglomeration and performance deterioration. The carbon-coated β-Si3 N4 /Si composite anode shows specific capacities of 1068 and 480 mAh g-1 at 0.2 and 5 A g-1 , respectively. A full cell consisting of the carbon-coated β-Si3 N4 /Si anode and a LiNi0.8 Co0.1 Mn0.1 O2 cathode is constructed and its properties are evaluated. The potential of the proposed composite anodes for Li-ion battery applications is demonstrated.


Dialysis Access Evaluation.
The vascular lab (VL) provides vital information for dialysis access to guide management. This article discusses the indication, protocol, and diagnostic criteria for the evaluation of arteriovenous fistulas and grafts. An arteriovenous (AV) dialysis access is made by creating a connection between an artery and vein (AV fistula [AVF]) or by interposing a conduit between an artery and a vein (AV graft [AVG]) to provide high flow circuit for hemodialysis. A normal mature AV dialysis access has a thrill or vibration from turbulent flow in the graft or vein. The nomenclatures at our institution for an AVF and AVG are in the Figure 1 A and B diagrams.


Assessing the use of tumor-specific DARPin-toxin fusion proteins for ex vivo purging of cancer metastases from human ovarian cortex before autotransplantation.
To assess the use of tumor-specific designed ankyrin repeat proteins (DARPins) fused to a domain of Pseudomonas aeruginosa exotoxin A for purging of cancer metastases from the ovarian cortex. Experimental study. University medical center. Human ovarian cortex. Ovarian cortex harboring artificially induced breast cancer metastases was treated with DARPins targeted to epithelial cell adhesion molecule (EpCAM) and human epidermal growth factor receptor 2 (HER2). The presence of any remaining cancer cells after purging was analyzed by (immuno)histochemistry and reverse transcriptase polymerase chain reaction. Effects on the viability of the ovarian cortex were determined by (immuno)histology, a follicular viability assay, and an assay to determine the in vitro growth capacity of small follicles. After purging with EpCAM-targeted DARPin, all EpCAM-positive breast cancer cells were eradicated from the ovarian cortex. Although treatment had no effect on the morphology or viability of small follicles, a sharp decrease in oocyte viability during in vitro growth was observed, presumably due to low-level expression of EpCAM on oocytes. The HER2-targeted DARPins had no detrimental effects on the morphology, viability, or in vitro growth of small follicles. HER2-positive breast cancer foci were fully eliminated from the ovarian cortex, and the reverse transcriptase polymerase chain reaction showed a decrease to basal levels of HER2 mRNA after purging. Purging cancer metastases from ovarian cortex without impairing ovarian tissue integrity is possible by targeting tumor cell surface proteins with exotoxin A-fused DARPins. By adapting the target specificity of the cytotoxic DARPin fusions, it should be possible to eradicate metastases from all types of malignancies.


Comparative Study of Community Acquired and Nosocomial Spontaneous Bacterial Peritonitis and its Variants in 150 Patients.
Nosocomial acquisition of spontaneous bacterial peritonitis (SBP) is debated as having a different microbial etiology and prognosis. Identification of clinical, laboratory predictors of mortality and appropriate empirical antimicrobial selection is necessary to prevent early mortality and morbidity. We aimed to find the clinical and bacteriological profile in nosocomial and community acquired SBP and its variants, and the predictors of mortality. One hundred and fifty patients with 162 discrete episodes of different types of SBP were analyzed. Relevant clinical and laboratory data were analyzed. SBP was diagnosed according to standard criteria and classified as community acquired if the infection detected within 48 h of admission and as nosocomial after 48 h of admission to the hospital. Eighty seven percent had community acquired SBP (CSBP), 13% had nosocomial SBP (NSBP). Patients of NSBP were older, had more episodes of GI bleed and higher previous episodes of encephalopathy. Patients who died were older, had worse encephalopathy. NSBP had higher one month mortality. Age, serum sodium, encephalopathy and NSBP predicted mortality. Culture positivity was 22.22%. Escherichia coli was the commonest organism isolated. There was no difference in the bacteriological profile between CSBP and NSBP. E. coli showed up to 48% resistance to third generation cephalosporins. Overall sensitivity to aminoglycosides was more than 75%. Overall mortality was 59%. NSBP had significantly high one month mortality. Age, serum sodium, encephalopathy and NSBP were predictors of mortality. Bacteriological profile was similar between CSBP and NSBP.


Ancient medicinal plant rosemary contains a highly efficacious and isoform-selective KCNQ potassium channel opener.
Voltage-gated potassium (Kv) channels in the KCNQ subfamily serve essential roles in the nervous system, heart, muscle and epithelia. Different heteromeric KCNQ complexes likely serve distinct functions in the brain but heteromer subtype-specific small molecules for research or therapy are lacking. Rosemary (Salvia rosmarinus) is an evergreen plant used medicinally for millennia for neurological and other disorders. Here, we report that rosemary extract is a highly efficacious opener of heteromeric KCNQ3/5 channels, with weak effects on KCNQ2/3. Using functional screening we find that carnosic acid, a phenolic diterpene from rosemary, is a potent, highly efficacious, PIP2 depletion-resistant KCNQ3 opener with lesser effects on KCNQ5 and none on KCNQ1 or KCNQ2. Carnosic acid is also highly selective for KCNQ3/5 over KCNQ2/3 heteromers. Medicinal chemistry, in silico docking, and mutagenesis reveal that carboxylate-guanidinium ionic bonding with an S4-5 linker arginine underlies the KCNQ3 opening proficiency of carnosic acid, the effects of which on KCNQ3/5 suggest unique therapeutic potential and a molecular basis for ancient neurotherapeutic use of rosemary.


The effects of calcium and magnesium ions, temperature and repetitive stimulation on inhibitory junctional transmission in smooth muscle of guinea-pig small intestine.
1 The effects of calcium and magnesium ions and temperature on the peak amplitude of the nonadrenergic, noncholinergic inhibitory junction potential, evoked by a single stimulus, or paired transmural stimuli, were examined in the circular muscle of guinea-pig small intestine.2 The peak amplitude of the inhibitory junction potential (i.j.p.) could be decreased by lowering the external concentration of calcium or by raising the external magnesium concentration (at 25 degrees C).3 At 25 degrees C, the second of a pair of i.j.ps was larger than the first at short intervals (<0.2 s), but smaller at larger intervals (0.2 to 20 s). Enhancement of the second (test) response decayed exponentially with a time constant of 87 ms. Depression of the test i.j.p. was maximal at 0.4 s and then recovered exponentially with a time constant of 11 s.4 In low calcium or high magnesium solution, depression of the test i.j.p. decreased without any change in the rate of recovery from depression.5 Despite the slow rate of recovery from depression after a single conditioning response, transmitter output could be maintained during low-frequency repetitive stimulation.6 The peak amplitude of the i.j.p. increased as the temperature was raised to 35 degrees C (Q(10) = 1.5).7 In contrast to the neuromuscular junction, the depression of the second of a pair of i.j.ps decreased as the temperature was raised. At 35 degrees C the test i.j.p. was larger than the conditioning i.j.p. for most stimulus intervals (1 to 20 s).8 The results suggest that the rate of replenishment of the store of inhibitory transmitter is sensitive to both temperature and repetitive stimulation.


Non-concerted ITS evolution in Mammillaria (Cactaceae).
Molecular studies of 21 species of the large Cactaceae genus Mammillaria representing a variety of intrageneric taxonomic levels revealed a high degree of intra-individual polymorphism of the internal transcribed spacer region (ITS1, 5.8S rDNA, ITS2). Only a few of these ITS copies belong to apparently functional genes, whereas most are probably non-functional (pseudogenes). As a multiple gene family, the ITS region is subjected to concerted evolution. However, the high degree of intra-individual polymorphism of up to 36% in ITS1 and up to 35% in ITS2 suggests a non-concerted evolution of these loci in Mammillaria. Conserved angiosperm motifs of ITS1 and ITS2 were compared between genomic and cDNA ITS clones of Mammillaria. Some of these motifs (e.g., ITS1 motif 1, 'TGGT' within ITS2) in combination with the determination of GC-content, length comparisons of the spacers and ITS2 secondary structure (helices II and III) are helpful in the identification of pseudogene rDNA regions.


Neuroactive steroids and affective disorders.
Neuroactive steroids modulate neurotransmission through modulation of specific neurotransmitter receptors such as gamma-aminobutyric acid type A (GABA(A)) receptors. Preclinical studies suggested that neuroactive steroids may modulate anxiety and depression-related behaviour and may contribute to the therapeutical effects of antidepressant drugs. Attenuations of such neuroactive steroids have been observed during major depression and in several anxiety disorders, suggesting a pathophysiological role in such psychiatric conditions. In panic disorder patients a dysequilibrium of neuroactive steroid composition has been observed, which may represent a counterregulatory mechanism against the occurrence of spontaneous panic attacks. Furthermore, alterations of 3alpha-reduced pregnane steroids during major depression were corrected by successful treatment with antidepressant drugs. However in contrast, non-pharmacological antidepressant treatment strategies did not affect neuroactive steroid composition. In addition, changes in neuroactive steroid concentrations after mirtazapine therapy occurred independently from the clinical response, thereby suggesting that changes in neuroactive steroid concentrations more likely reflect direct pharmacological effects of antidepressants rather than clinical improvement in general. Nevertheless, the effects of antidepressant pharmacotherapy on the composition of neuroactive steroids may contribute to the alleviation of certain depressive symptoms, such as amelioration of anxiety, inner tension or sleep disturbances. Moreover, first studies investigating the therapeutical effects of dehydroepiandrosterone revealed promising results in the treatment of major depression. In conclusion, neuroactive steroids are important endogenous modulators of depression and anxiety and may provide a basis for development of novel therapeutic agents in the treatment of affective disorders.


Impact of a brief intervention to improve engagement in a recovery program for young adults with serious mental illness.
Serious mental illnesses (SMI) commonly emerge during young adulthood. Effective treatments for this population exist; however, engagement in treatment is a persistent challenge. This study examines the impact of Just Do You (JDY), an innovative intake-focused intervention designed to improve engagement in treatment and enhance personal recovery. The study used a parallel group randomized trial to examine if and how JDY improved recovery among 121 young adults with SMI from low-resourced communities referred to personalized recovery-oriented services (PROS). Measures of engagement (buy-in and attendance) and personal recovery in this pilot study were assessed at baseline and 3-month follow-up. Participants in JDY reported more positive engagement outcomes; that is, relative to the control group they reported higher past two week attendance (b = 0.72, p < 0.05, Cohen's d = 0.56) and higher levels of buy-in to treatment (b = 2.42, p < 0.05, Cohen's d = 0.50). JDY also impacted young adults' personal recovery (b = 0.99, p < 0.05, Cohen's d = 1.15) and did so largely by increasing their level of buy-in to the treatment program. This study suggests that an engagement intervention for young adults that orients, prepares, and empowers them to be active and involved in the larger treatment program makes a difference by improving engagement and enhancing recovery. Data also support conceptualizing and examining engagement beyond treatment attendance; in this study what mattered most for recovery was the level of buy-in to treatment among young adults.


Proteases in the schistosome life cycle: a paradigm for tumour metastasis.
Cancers and parasites have a number of properties in common, particularly those that relate to their respective capacities to evade host defence mechanisms. This review highlights the similarities between metastatic tumours and schistosomes in particular, and describes the role that proteases may have in the migration, growth, survival and transmission of the different stages of the schistosome life-cycle in the vertebrate host. An elastase-like serine protease of schistosome larvae has been particularly well characterized, and its substrate profile and other properties are indicative of a role in facilitating migration of the parasite through skin tissue early after infection. The primary structures of a cathepsin B-like enzyme, and a putative 'haemoglobinase' found in adult worms have also recently been derived, these enzymes being responsible for degradation of haemoglobin in erythrocytes upon which the adults feed. Adult schistosome worms reside and produce eggs intravascularly, and the processes that mediate the extravasation and subsequent migration of the egg through host tissue are dependent on both blood platelets and the immune response. Fibrino(geno)lytic enzymatic activity that is present in the egg could modulate the thrombogenic potential that eggs might have as a result of their capacity to cause platelet aggregation in vitro and in vivo. The roles of other proteases and peptidases that have been found in schistosome larvae, worms and eggs are less clear. Some of these enzymes may modulate immunological and haemostatic defence mechanisms and thus prolong survival of the parasite, and the consequences of the interactions between schistosomes and host protease inhibitors could also be immune modulatory.


hsa-miR-199b-3p suppresses osteosarcoma progression by targeting CCDC88A, inhibiting epithelial-to-mesenchymal transition, and Wnt/beta-catenin signaling pathway.
The present study investigated microRNA (miR)-199b-3p expression in osteosarcoma (OS) and aimed to identify its potential mechanism of action contributing to the development of this disease. Firstly, miR-199b-3p and coiled-coil domain containing 88A (CCDC88A) expression data were evaluated from Gene Expression Profiling Interactive Analysis and Kaplan Meier plotter was used to assess the survival data. By analyzing the GSE65071 dataset from gene expression omnibus, it was found that miR-199b-3p was expressed at a low level. By using reverse transcription-quantitative PCR analysis in OS cells and tissues, CCDC88A was found to be expressed at a high level. Moreover, TargetScan predicted CCDC88A to be a downstream target of miR-199b-3p. Luciferase reporter assays were used to verify this prediction. In vitro overexpression of miR-199b-3p decreased the invasive and proliferative activity of OS cells. Mechanistic studies indicated that decreased miR-199b-3p resulted in increased expression of CCDC88A. Concomitantly, it impeded the Wnt/beta-catenin pathway and the epithelial-to-mesenchymal transition process. Overall, the results of the present study emphasized the pivotal role of the miR-199b-3p in the formation and progression of OS, suggesting that it could be used as a potential tumor biomarker.


Effects of psychiatric disorders on ultrasound measurements and adverse perinatal outcomes in Chinese pregnant women: A ten-year retrospective cohort study.
Placental health and serial fetal ultrasound parameters deficits in fetal development in women with psychiatric disorders have yet to be understood. This study aimed to examine the effects of psychiatric disorders on placental health, ultrasound measurements, and adverse perinatal outcomes among Chinese pregnant women. All the pregnant women with psychiatric disorders who delivered at Women's Hospital School of Medicine, Zhejiang University, China, between 2010 and 2020 were included. A total of 992 women (716 in the healthy control group and 276 in the psychiatric disorders group) were recruited. Outcomes include maternal and neonatal birth outcomes. Linear and logistic regression models were used to determine the beta (β) and odds ratios (OR) across 2 models after adjusting for multiple covariates. For women with psychiatric diagnoses, the mean placental measurements and serial fetal ultrasound parameters, and neonatal birth weight were lower than general pregnant women. After controlling the use of psychotropic medication during pregnancy, women with psychiatric diagnoses showed higher rates of placental implantation abnormalities or placental adhesion (OR = 5.724, 95% CI = [1.805, 15.408]), gestational diabetes mellitus (OR = 3.861, 95% CI = [2.109, 7.068]), anemia in pregnancy (OR = 4.944, 95% CI = [2.306, 10.598]), preterm birth <37 weeks' gestation (OR = 3.200, 95% CI = [1.702, 6.016]), low birth weight (OR = 11.299, 95% CI = [4.068, 31.386]), and neonatal intensive care unit admission (OR = 3.143, 95% CI = [1.656, 5.962]) compared to women in the healthy control group. Pregnant women with psychiatric disorders were more likely to have poor placental outcomes, more ultrasound parameter abnormalities and obstetrical complications, and a higher risk for adverse birth outcomes.


Is there a relationship between internalized misogyny and premenstrual syndrome and dysmenorrhea in young women? A descriptive-relational study.
This study utilized a descriptive and relational design to determine the relationship between young women's experiences of premenstrual syndrome (PMS) and dysmenorrhea with internalized misogyny. A total of 487 individuals were accessed. Data were collected through the "Personal Information Form" prepared by the researchers, the "Functional and Emotional Measure of Dysmenorrhea" the "Premenstrual Syndrome Scale," and the "Internalized Misogyny Scale." The internalized misogyny scale mean score had significant effects on the functional and emotional measure of dysmenorrhea mean score (p < 0.05). The internalized misogyny scale mean score was found to have a statistically significant effect on the premenstrual syndrome scale (p < 0.05). This study found that young women's internalized misogyny was highly correlated with PMS and dysmenorrhea, and increased internalized misogyny also increased the severity of PMS and dysmenorrhea in young women.


The use of machine learning modeling, virtual screening, molecular docking, and molecular dynamics simulations to identify potential VEGFR2 kinase inhibitors.
Targeting the signaling pathway of the Vascular endothelial growth factor receptor-2 is a promising approach that has drawn attention in the quest to develop novel anti-cancer drugs and cardiovascular disease treatments. We construct a screening pipeline using machine learning classification integrated with similarity checks of approved drugs to find new inhibitors. The statistical metrics reveal that the random forest approach has slightly better performance. By further similarity screening against several approved drugs, two candidates are selected. Analysis of absorption, distribution, metabolism, excretion, and toxicity, along with molecular docking and dynamics are performed for the two candidates with regorafenib as a reference. The binding energies of molecule1, molecule2, and regorafenib are - 89.1, - 95.3, and - 87.4 (kJ/mol), respectively which suggest candidate compounds have strong binding to the target. Meanwhile, the median lethal dose and maximum tolerated dose for regorafenib, molecule1, and molecule2 are predicted to be 800, 1600, and 393 mg/kg, and 0.257, 0.527, and 0.428 log mg/kg/day, respectively. Also, the inhibitory activity of these compounds is predicted to be 7.23 and 7.31, which is comparable with the activity of pazopanib and sorafenib drugs. In light of these findings, the two compounds could be further investigated as potential candidates for anti-angiogenesis therapy.


Use of acellular dermal matrix for complicated ventral hernia repair: does technique affect outcomes?
The ideal technique for the use of AlloDerm (LifeCell Corp) in complicated ventral hernia repair has not been defined. The expense of these products mandates careful evaluation to justify their widespread use. We compared two techniques of fascial bridging versus fascial reinforcement repair with regard to their longterm recurrence rates using AlloDerm. We retrospectively studied patients with abdominal defects repaired with AlloDerm at our institution. Thirty-seven patients with abdominal wall repairs using AlloDerm were identified between January 2004 and December 2005. Eleven patients underwent bridged fascial repair; 26 patients had reinforced fascial repair. There was no statistical significance between the 2 groups in terms of average age (57 versus 52 years), body mass index (35 versus 29 kg/m(2)), American Society of Anesthesiologists score (2.9 versus 2.5), or number of earlier abdominal operations (3.4 versus 3.5). The average sizes of AlloDerm used were 175 cm(2) for bridged and 89 cm(2) for reinforced repair (p=0.005). In patients with reinforced closure, primary repair was achieved with lateral component separation in 22 of 26 patients. Mean followup was 21.4 months (range 15 to 36 months). In the bridged group, 1 patient died on postoperative day 20. Of the remaining 10 patients, 8 patients (80%) developed recurrences. Seven patients required reoperation, but one patient refused repair. In the reinforced group, four patients were lost to followup and two patients died. Four of the remaining 20 patients (20%) developed recurrences that required repair; this was significantly different from the recurrence rate in the bridged group (p=0.009). This study demonstrated that the method in which AlloDerm is used in abdominal wall reconstruction has a significant impact on recurrence rates. Based on our findings, AlloDerm should be used only as a reinforcement after primary fascial reappoximation.


An ELISA for pregnancy-associated plasma protein A.
An enzyme-linked immunoassay for pregnancy-associated plasma protein A is described. The assay is sensitive (7.6 IU/l) and precise (overall CV varied between 8.9% and 10.8%). Recovery was 100% over the working range. Parallel behaviour was observed between the International Reference Preparation 78/610 and pregnancy serum, thus allowing calibration of a laboratory standard pool against IRP 78/610.


Publisher Correction: Clonal evolution of acute myeloid leukemia revealed by high-throughput single-cell genomics.
A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-19902-7.


CPSP-tools--exact and complete algorithms for high-throughput 3D lattice protein studies.
The principles of protein folding and evolution pose problems of very high inherent complexity. Often these problems are tackled using simplified protein models, e.g. lattice proteins. The CPSP-tools package provides programs to solve exactly and completely the problems typical of studies using 3D lattice protein models. Among the tasks addressed are the prediction of (all) globally optimal and/or suboptimal structures as well as sequence design and neutral network exploration. In contrast to stochastic approaches, which are not capable of answering many fundamental questions, our methods are based on fast, non-heuristic techniques. The resulting tools are designed for high-throughput studies of 3D-lattice proteins utilising the Hydrophobic-Polar (HP) model. The source bundle is freely available 1. The CPSP-tools package is the first set of exact and complete methods for extensive, high-throughput studies of non-restricted 3D-lattice protein models. In particular, our package deals with cubic and face centered cubic (FCC) lattices.


SOX-1 antibodies in a patient with Crohn's disease: a case report.
The anti-SOX-1 antibodies have been mainly associated with Lambert-Eaton Myasthenic Syndrome (LETMS) and Small-Cell Lung Cancer (SCLC). In this report, we describe the interesting case of a patient with serum anti-SOX-1 antibodies and Crohn's Disease (CD) with ensuing neurological symptoms. A Caucasian 67-year-old female was admitted to the Emergency Department with seizures, vertigo, emesis, nausea, postural instability and recurrent falls, over a period of 10 days. She had been affected by Crohn's Disease since 1991. A CT scan failed to detect any ischemic or haemorrhagic lesion. A brain MRI revealed signs of leukoencephalopathy. Western blot analysis of her serum revealed a high titre of the onconeural antibody anti-SOX1, consistent with a neurological, cerebellar type, paraneoplastic syndrome. In spite of multiple efforts to unmask a possible underlying malignancy, no neoplastic lesion cropped up during hospitalization. Her clinical conditions progressively deteriorated, up to respiratory failure; a few days later she died, due to ensuing septic shock and Multiple Organ Failure. Our experience may usher and reveal a new role of anti-neural antibodies, so far reckoned an early indicator of associated malignancy, suggesting that neurological syndromes associated with such antibodies may complicate also chronic Gastrointestinal (GI) diseases. As of now, testing for anti-neuronal antibodies appeared unnecessary within the diagnostic assessment of gastroenterological disorders, which may lead to overlooking incident neurologic autoimmune diseases. Further exploration of such research hypothesis in clinical grounds appears intriguing.


The emergency department ECG and immediately life-threatening complications in initially uncomplicated suspected myocardial ischemia.
The emergency physician's disposition of patients with suspected myocardial ischemia is currently debated; some physicians believe that a subgroup of patients can be managed safely outside the coronary care unit. Clinical predictors are needed in assessing the patient with suspected myocardial ischemia to help identify this subgroup. Through a retrospective cohort study, we investigated the value of the initial emergency department ECG in discriminating between chest pain patients with low and high risk for immediately life-threatening complications. Two hundred eleven initially uncomplicated consecutive coronary care unit admissions with suspected unstable angina or myocardial infarction were studied. Patient outcome, including the incidence of myocardial infarction, complications, and mechanical and pharmacologic interventions, was reviewed. Immediately life-threatening complications included ventricular fibrillation, ventricular tachycardia, shock, 2 degrees and 3 degrees block, and death. Mechanical interventions included electrocardioversion or defibrillation, endotracheal intubation, intra-aortic balloon pump, Swan-Ganz catheter, or pacemaker insertion. Pressors, antiarrhythmics, and vasodilators were the reviewed pharmacologic interventions. A positive ECG was defined by the presence of ST elevation or depression, T wave inversion, left ventricular hypertrophy, left bundle branch block, paced rhythm, or new Q waves. All other ECG interpretations were considered negative. Patients were divided into two groups based on this initial emergency physician ECG interpretation and their complication incidences compared. Of the 211 patients, 96 had a positive ECG; 115 had negative ECGs. Patients with positive ECGs were older, had a greater history and concurrent incidence of myocardial infarction, and more complications and intensive interventions.(ABSTRACT TRUNCATED AT 250 WORDS)


Bone critical defect repair with poloxamine-cyclodextrin supramolecular gels.
The aim of this study was to evaluate the osteoinductive capacity of a poloxamine (Tetronic(®) 908, T) and α-cyclodextrin (αCD) supramolecular gel (T-CD) as scaffold in a critical size defect in rat calvaria. The T-CD gel was evaluated solely and after being loaded with simvastatin (SV) and bone morphogenetic protein (BMP-2) separately and in combinations in order to reduce the doses of the active substances. Three doses of SV (7.5, 75, 750 μg) and two doses of BMP-2 (3 and 6 μg) were tested. The histology and histomorphometrical analysis showed improved bone repair with T-CD compared to T, probably due to better release control of both SV and BMP-2. In addition, as T-CD eroded more slowly than poloxamine alone, it remained longer in the defect site. Although synergism was not obtained with BMP-2 and SV, according to the observed regeneration of the defect, the dose of BMP-2 and SV can be reduced to 3 μg and 7.5 μg, respectively.


Comparison of video-stylet and conventional laryngoscope for endotracheal intubation in adults with cervical spine immobilization: A PRISMA-compliant meta-analysis.
Although minimization of cervical spine motion by using a neck collar or manual in-line stabilization is recommended for urgent tracheal intubation (TI) in patients with known or suspected cervical spine injury (CSI), it may worsen glottic visualization. The overall performance of video-stylets during TI in patients with neck immobilization remains unclear. The current meta-analysis aimed at comparing the intubation outcomes of different video-stylets with those of conventional laryngoscopes in patients with cervical immobilization. The databases of Embase, Medline, and the Cochrane Central Register of Controlled Trials were searched from inception to June 2021 to identify trials comparing intubation outcomes between video-stylets and conventional laryngoscopes. The primary outcome was first-pass success rate, while secondary outcomes included overall success rate, time to intubation, the risk of intubation-associated sore throat, or tissue damage. Five randomized controlled trials published between 2007 and 2013 involving 487 participants, all in an operating room setting, were analyzed. The video-stylets investigated included Bonfils intubation fiberscope, Levitan FPS Scope, and Shikani optical stylet. There was no difference in first-pass success rate (risk ratio [RR] =1.08, 95% confidence interval [CI]: 0.89-1.31, P = .46], overall success rate (RR = 1.06, 95% CI: 0.93-1.22, P = .4), intubation time [mean difference = 4.53 seconds, 95% CI: -8.45 to 17.51, P = .49), and risk of tissue damage (RR = 0.46, 95% CI: 0.16-1.3, P = .14) between the 2 groups. The risk of sore throat was lower with video-stylets compared to that with laryngoscopes (RR = 0.45, 95% CI: 0.23-0.9, P = .02). Our results did not support the use of video-stylets as the first choice for patients with neck immobilization. Further studies are required to verify the efficacy of video-stylets in the nonoperating room setting.


Creatinine clearance prediction in spinal cord injury patients: comparison of 6 prediction equations.
The renal function of spinal cord injury patients frequently is overestimated by 3 commonly used equations to predict creatinine clearance. Overestimation of creatinine clearance may result in aminoglycoside overdosage and resultant nephrotoxicity. Three newer prediction equations have been developed from creatinine clearances measured in neurologically abnormal patients. These 6 equations were tested in 77 male and 9 female spinal cord injury patients (48 quadriplegics and 38 paraplegics, including 38 with acute and 48 with chronic injuries). The equation developed by Sawyer and Hutchins was superior to 2 other equations developed in spinal cord injury patients and 3 equations developed in neurologically normal patients. However, creatinine clearances predicted by this equation were within 30 ml. per minute of measured creatinine clearances in only two-thirds of the spinal cord injury patients. Errors ranged from overestimation by 95 ml. per minute (151 per cent) to underestimation by 106 ml. per minute (45 per cent). The potential for large errors in creatinine clearance prediction necessitates measurement of creatinine clearance as soon as possible when renal excreted and toxic pharmaceuticals are administered to spinal cord injury patients.


Investigating the Association Between rs2439302 Polymorphism and Thyroid Cancer: A Systematic Review and Meta-Analysis.
The extent of surgical treatment for most patients with thyroid cancer (TC) remains controversial and varies widely. As an emerging technology, genetic testing facilitates tumor typing and disease progression monitoring and is expected to influence the choice of surgical approach for patients with TC. Recent genome-wide association studies (GWASs) have identified that rs2439302 (8p12) variants near NRG1 are associated with TC risk; however, the results remain inconclusive. Therefore, we aimed to perform a meta-analysis to clarify the association between rs2439302 variants and the risk of TC. We search eligible studies using Pubmed, Scopus, Embase, Web of Science, and Cochrane library by July 2021. We analyzed the pooled OR and the corresponding 95% confidence interval (95% CI) of the included studies and then conducted subgroup analysis according to the ethnicity. We also performed a sensitivity analysis to validate the findings. This meta-analysis finally included 7 studies involving 6,090 cases and 14,461 controls. Results showed that the G allele of the rs2439302 polymorphism was a significant risk factor of TC in Allele (G/C), Dominant (GG+GC/CC), Recessive (GG/GC+CC), Homozygote (GG/CC), Heterozygote (GC/CC) models, with pooled ORs of 1.38 (95%CI, 1.31-1.45), 1.51 (95%CI, 1.41-1.62), 1.52 (95%CI, 1.40-1.66), 1.90 (95%CI, 1.71-2.10), and 1.40 (95%CI, 1.30-1.51), respectively. The subgroup analysis showed that rs2439302 polymorphism was associated with higher TC risk in different ethnicities with OR > 1. The sensitivity analysis exhibited that the results were stable by omitting any included studies. The study revealed that rs2439302 variants were associated with higher TC risk and may have a major influence on the choice of operative approach for patients with TC.


The long-term follow-up results of external dacryocystorhinostomy skin incision scar with "W incision".
To determine the effect of "W incision" instead of classical vertical incision at external DCR on scar formation. Patients with acquired nasolacrimal duct obstruction (NLDO) who were treated with external DCR with classical vertical incision, and patients who were treated with external DCR with "W incision" were included in the study. The first 39 eyes were operated with a vertical incision, and the remaining 37 eyes were operated with a "W incision". All the skin incision scars of the patients were assessed and scored by at least the 6th month. The assessment was made by both the patients themselves, and by an ophthalmologist other than the surgeon himself, each scored the incision scar separately (single-masked study). Scores for both groups were compared, and statistical analyses were performed. Self-assessment scores for the incision scar were Grade 2.28 ± 0.94 in the Vertical incision group, and Grade 1.68 ± 0.57 in the "W incision" group (p < 0.01). The "W incision" scar formation was significantly less noticable than the Vertical incision scar formation. Similarly, the assessment scores of the ophthalmologist other than the surgeon himself were significantly lower for the "W incision" group than for the Vertical incision group. The mean scar assessment scores were Grade 2.13 ± 0.95 in the Vertical incision group, and Grade 1.57 ± 0.68 in the "W incision" group (p < 0.01). Skin scar tissue was found to be significantly reduced with a "W incision" in external DCR operations.


Chyloperitoneum with collateral lymphatic drainage involving abdominal skin.
A 58-year-old man with poorly differentiated lymphoma and chyloperitoneum, who developed periumbilical white vesicular skin lesions, is presented. These skin lesions represent collateral lymphatic drainage pathways for the chyloperitonium as evidenced by drainage of chylous fluid from these lesions and communication with the peritoneum as demonstrated by intraperitoneal 99mTc sulfur colloid injection.


Serial and parallel convolutional neural network schemes for NFDM signals.
Two conceptual convolutional neural network (CNN) schemes are proposed, developed and analysed for directly decoding nonlinear frequency division multiplexing (NFDM) signals with hardware implementation taken into consideration. A serial network scheme with a small network size is designed for small user applications, and a parallel network scheme with high speed is designed for places such as data centres. The work aimed at showing the potential of using CNN for practical NFDM-based fibre optic communication. In the numerical demonstrations, the serial network only occupies 0.5 MB of memory space while the parallel network occupies 128 MB of memory but allows parallel computing. Both network schemes were trained with simulated data and reached more than 99.9% accuracy.


Influenza Burden and Transmission in the Tropics.
Each year, influenza causes substantial mortality and morbidity worldwide. It is important to understand influenza in the tropics because of the significant burden in the region and its relevance to global influenza circulation. In this review, influenza burden, transmission dynamics, and their determinants in the tropics are discussed. Environmental, cultural, and social conditions in the tropics are very diverse and often differ from those of temperate regions. Theories that account for and predict influenza dynamics in temperate regions do not fully explain influenza epidemic patterns observed in the tropics. Routine surveillance and household studies have been useful in understanding influenza dynamics in the tropics, but these studies have been limited to only some regions; there is still a lack of information regarding influenza burden and transmission dynamics in many tropical countries. Further studies in the tropics will provide useful insight on many questions that remain.


[Are simple time lags responsible for cyclic variation of population density? : A comparison of laboratory population dynamics of Brachionus calyciflorus pallas (rotatoria) with computer simulations].
Laboratory populations of the rotifer Brachionus calyciflorus were cultured at different temperatures (25, 20, 15°C) but otherwise at constant conditions. The population densities showed relatively constant oscillations (Figs. 1 to 3A-C). Amplitudes and frequencies of the oscillations were positively correlated with temperature (Table 1). A test was made, whether the logistic growth function with simple time lag is able to describe the population curves. There are strong similarities between the simulations (Figs. 1-3E) and the real population dynamics if minor adjustments of the empirically determined parameters are made. There-fore it is suggested that time lags are responsible for the observed oscillations. However, the actual time lags probably do not act in the simple manner of the model, because birth and death rates react with different time lags, and both parameters are dependent on individual age and population density. A more complex model, which incorporates these modifications, should lead to a more realistic description of the observed oscillations.


Advances in humeomics: enhanced structural identification of humic molecules after size fractionation of a soil humic acid.
We size fractionated a soil humic acid (HA) by preparative high performance size exclusion chromatography (HPSEC) and evaluated the analytical capacity of humeomics to isolate and identify humic molecular components in the separated size-fractions. HA and its three size-fractions were chemically fractionated to extract non-covalently bound organosoluble compounds (ORG1), weakly ester-bound organosoluble (ORG2) and hydrosoluble constituents (AQU2), strongly ester-bound organosoluble components (ORG3), and final unextractable residues (RES4). According to their solubility, the extracts were characterized by either GC-MS or on-line thermochemolysis/GC-MS techniques. The humeomic sequence showed that the analytical yields of identified compounds in either ORG or AQU extracts of size-fractions were invariably larger than for the unfractionated HA. This was attributed to a weaker conformational stability of humic suprastructures obtained by HPSEC fractionation, thereby enabling an improved separation and identification of single humic molecules. In line with the supramolecular understanding of humic substances, we found that hydrophobic compounds were mainly distributed in the largest size-fraction, while hydrophilic components were eluted in the smallest size-fraction. Furthermore, compounds with linear chains or stackable aromatic rings associated in regular structures were more abundant in the former fraction, whereas irregularly shaped compounds, that hindered association in larger size, were mostly found in the latter fraction. Thus the structural characteristics of single humic molecules determined their mutual association in humic suprastructures, as well as their conformational strength and shape. The lack of de novo synthesized macropolymers in the unfractionated soil humic matter was confirmed by the absence of RES4 fractions in the separated size-fractions. Our results indicate that humeomics capacity to reveal the complex molecular composition of humic suprastructures was significantly improved by subjecting humic matter to a preliminary HPSEC fractionation.


The IAA- and ABA-responsive transcription factor CgMYB58 upregulates lignin biosynthesis and triggers juice sac granulation in pummelo.
In citrus, lignin overaccumulation in the juice sac results in granulation and an unpleasant fruit texture and taste. By integrating metabolic phenotyping and transcriptomic analyses, we found 702 differentially expressed genes (DEGs), including 24 transcription factors (TFs), to be significantly correlated with lignin content. CgMYB58 was further identified as a critical R2R3 MYB TF involved in lignin overaccumulation owing to its high transcript levels in Huanong Red-fleshed pummelo (HR, Citrus grandis) fruits. Transient expression of CgMYB58 led to an increase in the lignin content in the pummelo fruit mesocarp, whereas its stable overexpression significantly promoted lignin accumulation and upregulated 19 lignin biosynthetic genes. Among these genes, CgPAL1, CgPAL2, Cg4CL1, and CgC3H were directly modulated by CgMYB58 through interaction with their promoter regions. Moreover, we showed that juice sac granulation in pummelo fruits could be affected by indole-3-acetic acid (IAA) and abscisic acid (ABA) treatments. In HR pummelo, ABA significantly accelerated this granulation, whereas IAA effectively inhibited this process. Taken together, these results provide novel insight into the lignin accumulation mechanism in citrus fruits. We also revealed the theoretical basis via exogenous IAA application, which repressed the expression of CgMYB58 and its target genes, thus alleviating juice sac granulation in orchards.