Immunohistochemical localization of delta sleep-inducing peptide-like immunoreactivity in the central nervous system and pituitary of the frog Rana ridibunda.
The purpose of the present study was to investigate the distribution of delta sleep-inducing peptide in the brain and pituitary of the frog Rana ridibunda and to determine the possible effect of this nonapeptide on adrenocorticotropic hormone and corticosteroid secretion. Delta sleep-inducing peptide-like immunoreactive fibres were observed throughout the brain of the frog. These fibres generally exhibited the characteristics of glial cell processes. Scarce delta sleep-inducing peptide-positive fibres were seen in the olfactory bulb and in the periventricular areas of the telencephalon. In the diencephalon, numerous delta sleep-inducing peptide-containing processes were noted in the preoptic nucleus, the infundibular nuclei and the median eminence. A few cerebrospinal fluid-contacting cells were visualized in the ventral nucleus of the infundibulum. Delta sleep-inducing peptide-positive fibres were also observed in the mesencephalon, radiating through the different layers of the tectum. In the cerebellum, all Purkinje cells exhibited delta sleep-inducing peptide-like immunoreactivity. More caudally, numerous delta sleep-inducing peptide-positive fibres were noted in the vestibular nucleus of the rhombencephalon. A dense network of delta sleep-inducing peptide-containing fibres was seen in the pars nervosa of the pituitary. In the distal lobe, a population of endocrine cells located in the anteroventral region contained delta sleep-inducing peptide-immunoreactive material. Labelling of consecutive sections of the pituitary by delta sleep-inducing peptide and adrenocorticotropic hormone antiserum revealed that a delta sleep-inducing peptide-related peptide is expressed in corticotroph cells. The possible role of delta sleep-inducing peptide in the control of adrenocorticotropic hormone and corticosteroid release was studied in vitro, using the perifusion system technique. Administration of graded doses of delta sleep-inducing peptide (from 10(-8) to 10(-6) M) to perifused frog anterior pituitary cells did not affect the spontaneous release of adrenocorticotropic hormone. In addition, prolonged infusion of delta sleep-inducing peptide (10(-6) M) did not alter the stimulatory effect of corticotropin-releasing factor (10(-7) M) on adrenocorticotropic hormone secretion. Similarly, exposure of frog interrenal slices to delta sleep-inducing peptide did not induce any modification of spontaneous or adrenocorticotropic hormone-evoked secretion of corticosterone and aldosterone. Our results provide the first evidence for the presence of a delta sleep-inducing peptide-related peptide in lower vertebrates. The occurrence of delta sleep-inducing peptide-like immunoreactivity in specific areas of the brain suggests that the peptide may act as a neuromodulator.(ABSTRACT TRUNCATED AT 400 WORDS)


The Perceived Impact of Iron Deficiency and Iron Therapy Preference in Exercising Females of Reproductive Age: A Cross-Sectional Survey Study.
Patient perceptions of iron deficiency and efficacy of iron therapy may differ from the interpretations of doctors. Qualitative investigation at an individual level related may help define patient expectations and therapeutic targets. Therefore, we aimed to explore this concept in exercising females of reproductive age. Exercising females (n = 403) who either (a) were currently experiencing iron deficiency, or (b) have experienced iron deficiency in the past were included. A survey comprising open-ended text response questions explored three 'domains': (1) the impact of iron deficiency, (2) the impact of iron tablet supplementation (where applicable), and (3) the impact of iron infusion treatment (where applicable). Questions were asked about training, performance, and recovery from exercise. Survey responses were coded according to their content, and sentiment analysis was conducted to assess responses as positive, negative, or neutral. Exercising females showed negative sentiment toward iron deficiency symptoms (mean range = -0.94 to -0.81), with perception that fatigue significantly impacts performance and recovery. Iron therapies were perceived to improve energy, performance, and recovery time. Participants displayed a strong positive sentiment (mean range = 0.74 to 0.79) toward iron infusion compared to a moderately positive sentiment toward oral iron supplementation (mean range = 0.44 to 0.47), with many participants perceiving that oral iron supplementation had no effect. In Australia, women prefer an iron infusion in treatment of iron deficiency compared to oral iron.


Metabolic regulation mechanism of Aconiti Radix Cocta extract in rats based on 1H-NMR metabonomics.
To establish a metabonomics research technique based on the combination of 1H-NMR and multivariate statistical analysis, so as to explore the metabolic regulation mechanism of Aconiti Radix Cocta extract (ARCE) in rat tissues and serum. SD rats were randomly divided into blank group, female group and male group. The 1H-NMR technique was used to collect the information of rat tissues and serum samples in each group. The principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA) and other methods were used for data pattern recognition, so as to screen out potential differential metabolites and metabolic pathways, and then network analysis and KEGG database were used to analyze the relationship between metabolites, metabolic pathways and diseases. The external features and 1H-NMR analysis showed that the sex of rats had no obvious effect on the drug action. A total of 15 potential differential metabolites and six metabolic pathways were screened out through data pattern recognition. Through network analysis and KEGG pathway analysis, three target diseases closely related to differential metabolites were found, and the metabolic pathway related to lung cancer was the central carbon metabolism of cancer. This study shows that Aconiti Radix Cocta (ARC) may regulate the energy metabolism of the body by influencing arginine synthesis, so as to play the roles of anti-inflammation, analgesia, anti-tumor and immune regulation.


Inflammatory activation and cholinergic anti-inflammatory system in eating disorders.
Dysfunctional serotoninergic regulation and hypothalamic-pituitary-adrenal (HPA) axis overreactivity have been consistently reported in research studies with eating disorders (ED). In addition, the links between stress response, serotonin function, HPA axis and inflammatory mechanisms in ED have also been suggested in a number of studies. In our study, inflammatory parameters in white blood cells were investigated in 26 female patients with ED and 25 healthy control subjects matched for sex, age and ethnicity. Patients were free of medication for at least two weeks at the time of the study. Results showed a significant increase in plasma levels of the proinflammatory cytokine IL1β and the protein expression of cyclooxygenase 2 (COX2) in peripheral mononuclear blood cells (PMBCs) in ED patients compared with controls. As well as a significant increase of the oxidative-nitrosative marker TBARS (Thiobarbituric Acid Reactive Substances) in plasma. These findings were associated with increased expression of the alpha7 subunit of the nicotinic receptor (α7nAChR) in PMBC in ED patients independent of plasma cotinine levels. These results suggest that a pro-inflammatory and oxidant phenotype might be present in ED patients. Further research on cellular inflammatory and anti-inflammatory pathways might be oriented to investigate differences between ED subtypes and to search for new potential targets for pharmacological treatment.


A high-throughput solid phase screening method for identification of lignocellulose-degrading bacteria from environmental isolates.
The development of cost-effective biofuels will require improvements in the efficiency of biomass deconstruction, a process typically carried out by lignocellulose-degrading enzymes. Environmental microbes represent an abundant and diverse source of lignocelluloses-degrading enzymes for use in biotechnology. However, identification of microorganisms that possess these enzymes has been slowed by a lack of rapid screening methodologies, particularly those that utilize native lignocellulosic substrates. In this report, we describe a new, solid-phase screening system for the identification of microbes capable of lignocellulose degradation. The critical component of this screening system is the use of acrylamide, instead of agar, as the solidifying agent. Our results show that this screening method allows for the identification of Gram-positive and Gram-negative bacteria that possess cellulose and hemicellulose degrading activities from environmental isolates.


Long-term declining in carbon monoxide (CO) at a rural site of Beijing during 2006-2018 implies the improved combustion efficiency and effective emission control.
Carbon monoxide (CO) is primarily the result of incomplete combustion, which has important impacts on the atmospheric chemical cycle and climate. Improved quantitative characterization of long-term CO trends is important for both atmospheric modeling and the design and implementation of policies to efficiently control multiple pollutants. Due to the limitations of high time-resolution and high-quality long-term observational data, studies on long-term trends in the CO concentration in China are quite limited. In this study, the observational data of the concentration of CO in a rural site of Beijing during 2006-2018 was used to analyze the long-term trend in CO concentration in Beijing. The Theil-Sen method and the generalized additive model (GAM)-based method, were used to conduct the trend estimation analysis. We found that the concentration of CO at the Shangdianzi site showed a significant downward trend during 2006-2018, with a decline rate of 22.8 ± 5.1 ppbV per year. The declining trend in CO also showed phasic characteristics, with a fast decreasing rate during the period of 2006-2008, stable variations during the period of 2009-2013 and a continuous downward trend after 2013. The declining trend in the CO concentration in the south to west (S-W) sectors where the polluted air masses come from is more rapid than that in the sectors where the clean air masses come from. The declining trend in the CO concentration implies the improved combustion efficiency and the successful air pollution control policies in Beijing and the surrounding area.


[Coumarin-induced necrotic purpura of the skin -- case report and review of the literature].
We report the case of a 28-year old woman with extensive red-black colored lesions of the skin on the left thigh, which appeared without trauma. The disease arrived during longterm coumarin therapy because of a deep vein thrombosis and an antiphospholipid syndrome. After consideration of the differential diagnoses and due to the typical clinical picture we made the diagnosis of coumarin necrosis. We review the clinical and therapeutic features for this rare complication.


Nuclear factor I and cerebellar granule neuron development: an intrinsic-extrinsic interplay.
Granule neurons have a central role in cerebellar function via their synaptic interactions with other neuronal cell types both within and outside this structure. Establishment of these synaptic connections and its control is therefore essential to their function. Both intrinsic as well as environmental mechanisms are required for neuronal development and formation of neuronal circuits, and a key but poorly understood question is how these various events are coordinated and integrated in maturing neurons. In this review, we summarize recent work on the role of the Nuclear Factor I family in the transcriptional programming of cerebellar granule neuron maturation and synapse formation. In particular, we describe (1) the involvement of this family of factors in key developmental steps occurring throughout postmitotic granule neuron development, including dendrite and synapse formation and synaptic receptor expression, and (2) the mediation of these actions by critical downstream gene targets that control cell-cell interactions. These findings illustrate how Nuclear Factor I proteins and their regulons function as a "bridge" between cell-intrinsic and cell-extrinsic interactions to control multiple phases of granule neuron development.


An association of actin isoforms with the expression of motile response in pigmentation variants induced from goldfish erythrophoroma cells.
Comparison of actin isoforms in unpigmented goldfish cells (a normal dermal fibroblast-like cell line, and an unpigmented erythrophoroma cell line capable of being induced to undergo melanization) and in normal and neoplastic melanized goldfish cells shows that the melanized phenotype is accompanied by the presence of multiple actin isoforms. In contrast, the unpigmented cells have only beta-actin. The possible significance of this to pigment organelle translocation is discussed.


SIRT1 regulation-it ain't all NAD.
SIRT1 is a phylogenetically conserved energy sensor. The molecular mechanisms that regulate its catalytic activity, however, are incompletely understood. Gerhart-Hines et al. (2011) have identified β-adrenergic/cAMP signaling as a regulatory input that rapidly controls SIRT1 activity and fatty acid oxidation.


The Magnitude and Potential Causes of Sex Disparities in Statin Therapy in Veterans with Type 2 Diabetes: A 10-year Nationwide Longitudinal Cohort Study.
Past research has shown that women eligible for statin therapy are less likely than their male counterparts to receive any statin therapy or be prescribed a statin at the guideline-recommended intensity. We compared statin treatment in men and women veterans from a national cohort of older veterans with type 2 diabetes. The Veterans Health Administration Corporate Data Warehouse and Centers for Medicare and Medicaid Services data were used to create a unique dataset and perform a longitudinal study of veterans with type 2 diabetes from 2007 to 2016. Mixed-effects logistic regression was used to model the association between the primary exposure (sex) and statin use. The study included 714,212 veterans with diabetes, including 9,608 women, with an overall mean age of 75.9 years. In the unadjusted model for any statin use, women veterans had a 14% significantly lower odds of having any statin use compared with men. After adjusting for all covariates, including markers of Veterans Administration care use (service-connected disability rating, Veterans Administration use, and primary care visits) that serve as proxies for access and mental health comorbidities (depression and psychiatric disorder), this disparity narrowed from 14% to 3% and was no longer statistically significant. In the model for high-intensity statin therapy (high-intensity vs. low or none), women were 10% less likely than men to use high-intensity statins in the base model that included only time and sex. After adjusting for all measured covariates, the direction of the association changed and women had 16% higher odds of high-intensity statin use compared with men (odds ratio, 1.16; 95% confidence interval, 1.03-1.31). Consistent with prior research, in the unadjusted analysis a significant sex disparity was observed in statin use, with lower rates observed in women. For the outcome of any statin use, after adjustment for covariates that included variables that are proxies for access as well as psychiatric and depression comorbidities, this disparity lost statistical significance and narrowed. In the high-intensity statin versus low or none model, the direction of the association changed after controlling for measured covariates and women had a 16% higher odds of high-intensity statin use compared with men. This study highlights a persistent health disparity in lipid-lowering therapy for women veterans. Additional research is needed to further elucidate the reasons for and develop interventions to mitigate this persistent sex disparity in cholesterol management for veterans with diabetes.


Combined retrosigmoid and middle fossa approach for a small, superiorly located petroclival meningioma: how I do it.
Petroclival meningiomas pose significant surgical challenges because of their deep location and complex surrounding neurovasculature. The use of multiple surgical approaches can optimize safe tumor removal from multiple anatomic compartments. We describe a patient with a growing superior petroclival meningioma centered at the posterior clinoid with extension into Meckel's cave that was successfully removed with a combined retrosigmoid and subtemporal middle fossa approach. This strategy avoided the need for anterior petrous bone drilling and tentorial splitting. A combined retrosigmoid and subtemporal middle fossa approach can provide safe access to tumors spanning the supra- and infratentorial compartments.


Sexual dysfunction in stroke patients.
A marked decline in sexual activity has been reported in stroke patients. Little information, however, is available on clinical correlates of sexual dysfunction, changes in the sexual life of spouses of stroke patients, and abnormalities of nocturnal penile erections. In this prospective 6-month follow-up study, we assessed the impact of stroke on libido, sexual arousal, coital frequency and satisfaction with sexual life in 50 stroke patients (38 men, 12 women, aged 32 to 65 years) and in their spouses. We also measured nocturnal penile erections of the male patients using a strain gauge attached around the penis. All the analyzed aspects of sexuality, i.e., libido, coital frequency, erection, ejaculation, vaginal lubrication, orgasm and satisfaction with sexual life, were commonly decreased as a consequence of stroke both in the patients and in their spouses. Fourteen (28%) patients at 2 months post-stroke and 6 (14%) patients at 6 months had ceased having sexual intercourse. Nocturnal erections at 2 months post-stroke were normal in 17 (45%) of the 38 male patients and impaired in 21 (55%) patients, but all of the patients had some nocturnal erections. Sexual dysfunction correlated significantly (P<0.05) with the presence of the sensory hemisyndrome. Sexual dysfunction and dissatisfaction with sexual life seems to be common both in male and female stroke patients and in their spouses. Decreased libido, sexual arousal and satisfaction are related particularly to the presence of the hemisensory syndrome. The etiology for sexual dysfunction after stroke is multifactorial including both organic and psychosocial factors.


NMDA and non-NMDA receptor antagonists inhibit photic induction of Fos protein in the hamster suprachiasmatic nucleus.
We previously reported that systemic treatment with a noncompetitive antagonist affecting the NMDA subtype of excitatory amino acid (EAA) receptor, MK-801, inhibits photic induction of Fos-like immunoreactivity (Fos-lir) in the hamster suprachiasmatic nucleus (SCN). Because MK-801 blocks the Ca2+ channel associated with the NMDA receptor, it may also influence the activity of other transmitters acting through Ca2+ channels. To assess the specificity of these effects, we compared the effects on photic induction of Fos-lir of several treatments: central injection of a competitive NMDA antagonist, CPP; central injection of a non-NMDA antagonist, DNQX; and systemic injection of the non-competitive NMDA antagonist, ketamine. Fos-lir was induced in SCN cells of vehicle-injected hamsters exposed to a light pulse 4-5 h after dark onset. Pretreatment with CPP (greater than 2 nmoles) or ketamine (greater than 100 mg/kg) caused a dose-related inhibition of photic induction of Fos-lir in portions of the SCN. These treatments reduced Fos-lir mainly in the rostral SCN and ventrolateral, but not dorsolateral, portions of the caudal SCN. Pretreatment with DNQX (greater than 20 nmoles) also inhibited photic induction of Fos-lir in the same regions of the SCN. These results indicate that photic induction of Fos protein in a portion of the hamster SCN is regulated by both NMDA and non-NMDA types of EAA receptor.


An intersubunit interaction regulates trafficking of rod cyclic nucleotide-gated channels and is disrupted in an inherited form of blindness.
A mutation in a cyclic nucleotide-gated channel (CNGA1) is associated with retinitis pigmentosa (RP), a common, inherited eye disease. Expression of mutant (CNGA1-RP) homomeric channels in Xenopus oocytes revealed no measurable differences compared to wild-type CNGA1 homomers. As native retinal rod CNG channels comprise CNGA1 and CNGB1 subunits, we coexpressed CNGA1-RP and CNGB1. Surprisingly, this subunit combination did not produce detectable channels at the membrane surface. We show that the mechanism underlying this defect involves an intersubunit interaction between CNGA1 and CNGB1 that was not formed between CNGA1-RP and CNGB1 subunits. In the absence of this interaction, a short N-terminal region in CNGB1 prevented membrane expression. Thus, disruption of a regulatory interaction by mutation in CNGA1 exposed a region of CNGB1 that disrupted surface expression of heteromeric CNGA1-RP/CNGB1 channels, accounting for this instance of RP.


Author Correction: PGBD5 promotes site-specific oncogenic mutations in human tumors.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Effects of vitamin B6 on growth, diarrhea rate, intestinal morphology, function, and inflammatory factors expression in a high-protein diet fed to weaned piglets1.
Vitamin B6 (VB6) is an important coenzyme factor which participates in many metabolic reactions, especially amino acid metabolism. There are few reports on how VB6 mediates weaned piglet intestinal health. This study purposed to investigate dietary VB6 effects on growth, diarrhea rates, and intestinal morphology and function in weaned piglets fed a high-crude protein (22% CP) diet. Eighteen 21-d-old weaned [(Yorkshire × Landrace) × Duroc] piglets with body weights of 7.03 ± 0.15 (means ± SEM) kg were randomly assigned into 3 VB6-containing dietary treatments. Vitamin B6 content was: 0, 4, and 7 mg/kg, respectively. The feeding period lasted 14 d. The results showed that no significant difference existed for the growth performance. The 7 mg/kg VB6 group had a tendency to decrease diarrhea rate (P = 0.065). Blood biochemical parameters analysis demonstrated that total protein, cholesterol, and high-density lipoprotein significantly increased in the 7 mg/kg VB6 group (P < 0.05). In the jejunum, no significant differences were detected for villus height, villus width, crypt depth, villus height and crypt depth ratios, and positive Ki67 counts and the mRNA expression of inflammatory cytokines. Vitamin B6 significantly increased the mRNA expression of SLC6A19 and SLC6A20 (P < 0.05) and decreased the mRNA expression of SLC36A1 (P < 0.05). In the ileum, VB6 significantly increased villus height and villus width (P < 0.05) while decreased positive Ki67 cell counts for 7 mg/kg VB6 group (P < 0.05). Vitamin B6 had significantly increased the mRNA expression of interleukin-1β, tumor necrosis factor-α,cyclo-oxygen-ase-2, and transforming growth factor-β (P < 0.05). Vitamin B6 also had significantly increased mRNA expression of SLC6A19, SLC7A6, SLC7A7, and SLC36A1 (P < 0.05). These findings suggest that dietary supplementation with VB6 may affect the intestinal morphology and absorption and metabolism of protein in weaned piglets fed a high-protein diet by altering the expression of intestinal inflammatory cytokines and amino acid transporters.


Dual effects of carbamazepine-phenytoin interaction.
By intrapatient comparison at constant phenytoin (PHT) dose, the effect of increased carbamazepine (CBZ) dose was studied in 32 epileptic outpatients treated with a combination of PHT and CBZ. The mean PHT plasma concentration, as well as the concentration/dose ratio for PHT, became significantly higher secondary to increased doses of CBZ (14.1 +/- 3.5 vs. 19.3 +/- 3.6 micrograms/ml and 2.8 +/- 1.0 vs. 3.9 +/- 1.4 micrograms/ml plasma per milligram/kilogram daily dose, respectively; p less than 0.001). Concomitantly, in spite of CBZ dose higher by 17.6%, the CBZ concentration increased by only 6.4%, and the CBZ concentration/dose ratio actually decreased by 10%. In contrast, by intrapatient comparison at constant CBZ dose, the effect of reduced PHT dose on CBZ was studied in 22 patients. The mean CBZ plasma concentration as well as the concentration/dose ratio for CBZ appeared significantly higher, with a concomitant reduction of PHT (6.7 +/- 1.6 vs. 8.6 +/- 1.6 micrograms/ml and 0.37 +/- 0.1 vs. 0.49 +/- 0.2 micrograms/ml plasma per milligram/kilogram daily dose, respectively; p less than 0.001). This simultaneous dual effect--inhibition of PHT metabolism by CBZ and induction of CBZ metabolism by PHT--can result in PHT intoxication along with a fall in CBZ plasma concentration to a subtherapeutic range. This effect may be avoided or reduced if the PHT concentration is adjusted to approximately 13 micrograms/ml before CBZ is added or increased.


Hospitals wise up when adding physician practices.
The feverish competition to buy doc practices in the '90s was disastrous for hospitals. This time around, CEOs are establishing clearer goals and smarter integration strategies.


Vowel quality changes produced by surrounding tone sequences.
In three experiments, we examined whether energy at the same frequency as one of a vowel's harmonics in the F1 region can be captured by a preceding or following sequence of tones. The position of the /I/-/E/ phoneme boundary along an F1 continuum was used to assess the extent of capture. The first two experiments showed that a sequence of tones at 500 Hz (56-msec duration at 10/sec) can perceptually remove added energy at 500 Hz from a steady vowel (F0 = 125 Hz) that forms part of the sequence. The effect is detectable with one preceding tone, asymptotes with four, and is greater when two tones follow the vowel than when none do. Rising and falling sequences of tones (at 62.5-Hz intervals or at whole-tone intervals) differ in their effect. Falling sequences behave much like constant tones at 500 Hz but with less effect, whereas rising sequences show no evidence of removing the added tone. The second experiment replicated the first and also showed that when the vowel is embedded in a rising or a falling sequence of tones that continue after it, the following tones have no effect. The third experiment suggested that the different effects found with rising versus falling sequences are qualitatively predictable on the basis of the additive effects of their constituent tones rather than by virtue of their contour. The experiments indicated that sequences of repeating tones are much more effective at capturing a harmonic from a vowel than are sequences that follow a simple pattern. This result may reflect the operation of a principle of least commitment in auditory grouping.


Chitosan-hydroxyapatite composites.
Bone repair or regeneration is a common and complicated clinical problem in orthopedic surgery. The importance of natural polymers such as chitosan and its derivatives, and minerals such as calcium phosphates has grown significantly over the last two decades due to its renewable and biodegradable source, increasing the knowledge and functionality of composites in technological and biomedical applications. The properties of bone in health and disease attract much attention. A great proportion of the population need those medical devices for hard tissue regeneration and/or replacement, the pressure on the health systems in all countries became substantial. The short review focus in biomaterials such as chitosan and calcium phosphates composites with excellent properties such as biocompatibility, biofunctionality, and non-antigenic, showing the feasibility and ideal material to treat musculoskeletal disorders for hard tissue regeneration.


Preliminary study of analgesic effect of bumetanide on neuropathic pain in patients with spinal cord injury.
The current study evaluated the analgesic effects of bumetanide as an adjunctive treatment in managing neuropathic pain following spinal cord injury. The peripheral expression level of Na-K-Cl-cotransporter-1 (NKCC1) and K-Cl-cotransporter-2 (KCC2) genes in polymorphonuclear lymphocytes (PMLs) assessed as a possible biomarker indicating central underlying mechanisms. This open-label, single-arm, pilot trial of bumetanide (2 mg/day) is an add-on treatment conducted in 14 SCI patients for 19 weeks. The whole duration consisted of three phases: pre-treatment (1 month), titration (3 weeks), and active treatment (4 months). Ultimately, nine patients completed the study. The primary outcome variables were the endpoint pain score measured by the numeric rating scale (NRS), and the short-form McGill Pain Questionnaire. Secondary endpoints included the Short-Form Health Survey that measures the quality of life. Blood samples were collected and used for determining the expression of NKCC1 and KCC2 genes in transcription and translation levels. Bumetanide treatment significantly reduced average pain intensity according to the NRS and the short form of the McGill Pain Questionnaire scores. The baseline expression of KCC2 protein was low between groups and increased significantly following treatment (P < 0.05). Through the current study, pain improvement accompanied by the more significant mean change from the baseline for the overall quality of life. These data might be a piece of preliminary evidence for the analgesic effect of bumetanide on neuropathic pain and could support the potential role of the upregulation of KCC2 protein and involvement of GABAergic disinhibition in producing neuropathic pain.


Immunoglobulin G4-related sclerosing cholecystitis presenting as gallbladder cancer: a case report.
Immunoglobulin G4 (IgG4)-related sclerosing disease is a systemic inflammatory syndrome, and an understanding of its characteristics is currently evolving. IgG4-related cholecystitis is a manifestation of IgG4-related sclerosing disease in the gallbladder. This case report describes the clinical, radiographic, and histopathological findings in a young male patient who presented with a synchronous mass in the gallbladder. Serum levels of IgG4 and the IgG4/IgG ratio were normal, and there was no associated autoimmune pancreatitis. Therefore, establishing a preoperative diagnosis of IgG4-related cholecystitis was very difficult, and a differential diagnosis of gallbladder cancer infiltrating the liver was suggested. Postoperative histopathological examination established a diagnosis of IgG4-related cholecystitis definitively. A preoperative diagnosis of IgG4-related cholecystitis, although possible, would have been highly challenging in this case. It is difficult to establish whether surgical intervention is necessary in IgG4-related cholecystitis. Because malignant tumors are frequently suspected with this clinical presentation, surgical intervention should be undertaken only after due deliberation.


Recent progress in understanding the genomic architecture of sexual conflict.
Genomic conflict between the sexes over shared traits is widely assumed to be resolved through the evolution of sex-biased expression and the subsequent emergence of sexually dimorphic phenotypes. However, while there is support for a broad relationship between genome-wide patterns of expression level and sexual conflict, recent studies suggest that sex differences in the nature and strength of interactions between loci are instead key to conflict resolution. Furthermore, the advent of new technologies for measuring and perturbing expression means we now have much more power to detect genomic signatures of sexual conflict. Here, we review our current understanding of the genomic architecture of sexual conflict in the light of these new studies and highlight the potential for novel approaches to address outstanding knowledge gaps.


Glucose and insulin responses during mixed meals or infusion of glucose in pregnant and lactating rats.
We studied the glucose tolerance in freely moving rats throughout pregnancy and lactation and during the first week after weaning. Dioestrous virgin rats served as controls. Basal glucose and insulin levels were determined after a 2-hr fasting period. Subsequently, the changes of the insulin and the glucose levels were determined during ingestion of a mixed ad lib meal or a 2 g mixed test meal, or during infusion of glucose (7.4 mg/min for 20 min) into the vena cava. Basal glucose levels were high during early pregnancy, low during late pregnancy, and in the normal range throughout lactation and after weaning. Basal insulin levels were decreased at the end of lactation. The results of the ad lib meal and test meal experiments were essentially the same. Glucose tolerance during meals was somewhat decreased early in pregnancy. The corresponding insulin responses greatly increased during the last week of pregnancy. Glucose tolerance during IV infusion of glucose was normal during pregnancy, but increased during lactation. Insulin responses to the infusion were increased during pregnancy and decreased during lactation. We concluded that glucose tolerance is hardly affected by pregnancy and even increases in the course of lactation. This is effected by an increased responsiveness of the B-cells to glucose during late pregnancy and by an increased turnover of glucose during lactation. We discuss to what extent the actions of progesterone, placental lactogen and prolactin may explain these adaptions of maternal metabolism.


Dispersive solid-phase extraction and dispersive liquid-liquid microextraction for the determination of flavor enhancers in ready-to-eat seafood by HPLC-PDA.
The dispersion solid-phase microextraction (DSPE) combined with dispersion liquid-liquid microextraction (DLLME) was developed as a rapid, simple and effective pretreatment method for the determination of flavor enhancers (maltol, ethyl maltol, vanillin, methyl vanillin, ethyl vanillin) of ready-to-eat seafood products (dried squid, baked squid, fried fish, steamed abalone). Under the optimized DSPE-DLLME method, the developed method exhibited low limits of quantitation (0.20-0.50 μg g-1) and excellent linearity (R2 ≥ 0.995). The recoveries of flavor enhancers in the actual samples were 83.7%-114.9%. Compared with traditional pretreatment methods, the developed DSPE-DLLME method was rapid (17 min) and easy to determine the flavor enhancers by high performance liquid chromatography with photodiode array detector (HPLC-PDA). In the actual samples, creamy compounds such as vanillin, methyl vanillin and ethyl vanillin were hardly found. However, the flavor compounds produced by thermal reactions such as maltol (except for dried squid 3) and ethyl maltol were present in all samples.


Induction of implantation in the mouse by intrauterine injection of adenosine monophosphate.
Like cyclic AMP or dibutyryl cyclic AMP, intrauterine administration of AMP (non-cyclic) induced implantation in ovariectomized, progesterone-treated mice.


The hazard of infection from the shared communion cup.
Interest and concern that the shared communion cup may act as a vehicle for indirectly transmitting infectious disease was reawakened when the human immunodeficiency virus (HIV) was detected in the saliva of infected persons. Bacteriological experiments have shown that the occasional transmission of micro-organisms is unaffected by the alcoholic content of the wine, the constituent material of the cup or the practice of partially rotating it, but is appreciably reduced when a cloth is used to wipe the lip of the cup between communicants. Nevertheless, transmission does not necessarily imply inoculation or infection. Consideration of the epidemiology of micro-organisms that may be transmitted via saliva, particularly the herpes group of viruses, suggests that indirect transmission of infection is rare and in most instances a much greater opportunity exists for direct transmission by other means. There is substantial evidence that neither infection with hepatitis B virus nor HIV can be transmitted directly via saliva so that indirect transmission via inanimate objects is even less likely. No episode of disease attributable to the shared communion cup has ever been reported. Currently available data do not provide any support for suggesting that the practice of sharing a common communion cup should be abandoned because it might spread infection.


Activation of the electrogenic sodium pump in guinea-pig atria by external potassium ions.
1. When cardiac preparations are rewarmed following prolonged hypothermia a transient hyperpolarization occurs in K-containing media. This hyperpolarization is correlated with the active Na efflux. It might be due to electrogenic Na pumping or to extracellular K depletion brought about by the activity of an electroneutral Na-K exchange pump. In order to distinguish between these mechanisms the effect of various extracellular K concentrations ([K](o)) on the membrane potential of guineapig atria was studied before and after hypothermia.2. The membrane potential increased with decreasing [K](o) before cooling. It reached values of -64 and -92 mV at 10.8 and 0 mM-K, respectively.3. The membrane hyperpolarized transiently after hypothermia beyong the potential observed before cooling. Maximal values of about -94 mV were obtained during rewarming in solutions containing 0.4-2.7 mM-K. The membrane potential was significantly lower (-88 mV) in K-free media. It was also diminished at [K](o) higher than 2.7 mM and was measured to be -74 mV at 10.8 mM-K.4. The hyperpolarization of the cell membrane during the first 20 min of rewarming was maximal at 2.7 mM-K and yielded 15.5 mV. The hyperpolarization amounted to 7.2 and 10 mV at 0.4 and 10.8 mM-K, respectively. No hyperpolarization occurred in K-free solutions.5. The rate of decline of the transient hyperpolarization increased with [K](o).6. Variations of membrane input resistance after changes in [K](o) were measured in rewarmed atrial trabecula. The measurements revealed an increase in membrane resistance in lower [K](o).7. It is concluded that the transient hyperpolarization of the cardiac cell membrane during rewarming is due to the activation of an electrogenic Na pump.8. The (relative) strength of the pump current at various [K](o) was derived from the observed dependence of the hyperpolarization and of the membrane input resistance on [K](o). The current is estimated to be half-maximal at about 1.5 mM-K.


Understanding the physics of hydrocolloids interaction using rheological, thermodynamic and functional properties: A case study on xanthan gum-cress seed gum blend.
Some rheological, thermodynamic and functional properties of selected hydrocolloids (xanthan gum-cress seed gum (XG-CSG)) blends at different ratios (1-0, 3-1, 1-1, 1-3, 0-1) were characterized to understand physically the biopolymers interaction and networks. XG showed a greater rigidity (elastic modulus, G'LVE = 58.60 Pa), total structural strength (complex modulus, G*LVE = 70.69 Pa), yield stress (limiting value of stress, τL = 7.58 Pa), emulsion capacity (EC = 6.78%) and foam stability (FC = 18.92%) than CSG (G'LVE = 7.05 Pa, G*LVE = 8.53 Pa, τL = 1.44 Pa, EC = 86.48% and FC = 14.98%), respectively. Among blends, 3-1 XG-CSG showed the highest G*LVE, foaming stability (FS) and the extent of recovery (Rr%). The results were summarized using the clustering technique and principal component analyses. The coefficient of the interaction of some parameters, Cole-Cole plots and Gibbs free energy changes (ΔG) of predisturbed and intact networks were investigated. In samples with an intact network, greater compatibility directly related to the extent of synergistic interaction, while in predisturbed samples, the lower compatibility directly related to the extent of synergistic interaction. Although all blends were highly incompatible with antagonistic behavior, 1-1 XG-CSG showed the lowest incompatibility (ΔG = 8028.60 J/mol) among samples with intact structure, while at disrupted state, 1-3 XG-CSG showed the lowest incompatibility (ΔG = 158.6 J/mol).


We have Neglected "Ourselves"; A Qualitative Study on Iranian Parents of Children with Aphakia.
Contact lenses play a substantial role in the management of childhood aphakia. However, the use and care of the lenses can be challenging. Despite its prevalence, the phenomenon of living with children with aphakia is not explained in Iran yet. The aim of this study was to illuminate the lived experience of the parents of children with aphakia. This hermeneutic phenomenological study was conducted on the parents who have been referred to Farabi Eye Hospital of Tehran, Iran in 2019, whose children were diagnosed with aphakia, and the condition was corrected with contact lenses. Qualitative semi-structured interviews were conducted with 20 parents of children with congenital cataract. Analysis was based on the framework of Diekelmann enabled data interpretation and elaboration of shared themes. The 20 parents involved in the study consisted of 12 women and 8 men. The participant's experiences were classified in 4 categories: Self-Ignorance, Troubled mind, Self-Regulation, and Coping with the problem while hoping for the future. "Self-Ignorance" and "Troubled Mind" indicates that because of the risk of burnout in the long-term process of treatment, the psychological support of parents is necessary. Psychological support will continue until the parents acquire the ability of self-regulation. Giving a realistic hope to families is a core element in psychological support.


Light guided procedure for congenital pyriform sinus fistula; new and simple procedure for impalpable fistula.
Pyriform sinus fistula causes acute suppurative thyroiditis, and there is a risk of recurrence if the sinus tract is not excised completely. The tract should be dissected as high as possible toward the pyriform fossa. We report our devised technique "the light guided procedure" for the impalpable fistula. A bronchoscope was inserted into the pyriform sinus fistula with the help of a gastrofiberscope positioned at the larynx. The tract of the fistula was identified with the help of the light from the bronchoscope. We were able to reach the proximal end of the fistula, directly. This procedure is easy, safe, and minimally invasive.


Case report: Malignant-type calcification of the nipple with histologic correlation.
Malignant-type calcification of the nipple is a rare lesion, with only 2 cases reported in literature. We present a case of a 48-year-old female who came to us because of noncycle breast pain, where malignant-type calcification of the nipple was incidentally seen on mammography. The final pathology is fibrocystic change with benign calcium in connective tissue. Different diagnosis of malignant and benign histology of malignant-type calcification with no associated mass is difficult or even not eligible so that wedge excision the nipple without making the deformity needs to perform to diagnose the histology.


Clinical impact of pharmacist-directed antimicrobial stewardship guidance following blood culture rapid diagnostic testing.
Rapid diagnostic testing (RDT) has been shown to be associated with improved clinical outcomes. To evaluate the clinical outcomes of using RDT paired with well-defined pharmacist-directed antimicrobial stewardship programme (ASP) guidance to achieve targeted treatment in patients with bacteraemia. In this quasi-study, a retrospective (pre-intervention) phase was compared with a prospective (post-intervention) phase. Adult patients with positive blood cultures identified using the BacT/ALERT system were included. Bacterial identification and susceptibility were provided by VITEK 2. During the post-intervention phase, Verigene ASP guidance was developed to optimize antibiotic selection. Pharmacists received the results from the microbiology laboratory, evaluated the appropriateness of current therapy (if any), and communicated the recommended antimicrobial therapy to the treating physician accordingly. The cohort consisted of 164 patients in the pre-intervention group and 148 patients in the post-intervention group. When comparing the post-intervention period with the pre-intervention period, the median time to culture identification was 22 vs 96 h (P<0.0001), median time to targeted antibiotics was 2 vs 22 h (P<0.0001), median time for antibiotic de-escalation was 12.2 vs 27 h (P<0.0001), and median time to escalation was 1.3 vs 24 h (P<0.003), respectively. In-hospital mortality and 30-day re-admission were significantly lower in the post-intervention group (P<0.003 and 0.034, respectively). Length of hospital stay was significantly shorter in the post-intervention group (6.5 vs 8 days; P=0.03). Rapid identification of bacteraemia combined with a pharmacist's recommendation as an ASP initiative significantly improved time to optimal therapy, and may have decreased the risk of mortality and re-admission.


Inhibition of nitric oxide synthesis by methylene blue.
Methylene blue appears to inhibit nitric oxide-stimulated soluble guanylyl cyclase and has been widely used for inhibition of cGMP-mediated processes. We report here that endothelium-dependent relaxation of isolated blood vessels and NO synthase-dependent cGMP formation in cultured endothelial cells were both markedly more sensitive to inhibition by methylene blue than effects induced by direct activation of soluble guanylyl cyclase. These discrepancies were also observed when superoxide dismutase (SOD) was present to protect NO from inactivation by superoxide anion. Subsequent experiments showed that formation of L-citrulline by purified NO synthase was completely inhibited by 30 microM methylene blue (IC50 = 5.3 and 9.2 microM in the absence and presence of SOD, respectively), whereas guanylyl cyclase stimulated by S-nitrosoglutathione was far less sensitive to the drug (50% inhibition at approximately 60 microM, and maximal inhibition of 72% at 1 mM methylene blue). Experimental evidence indicated that oxidation of NADPH, tetrahydrobiopterin or reduced flavins does not account for the inhibitory effects of methylene blue. Our data suggest that methylene blue acts as a direct inhibitor of NO synthase and is a much less specific and potent inhibitor of guanylyl cyclase than hitherto assumed.


Insights from an infodemiological study of mental health in Malaysia, the Philippines, Singapore, and Thailand from 2004 to 2021.
This infodemiological study utilized Relative Search Volumes (RSV) from Google Trends. It determined changes in public interest in mental health after the implementation of the mental health laws of Malaysia, the Philippines, Singapore, and Thailand using search volumes from 2004 to 2021. It found that public interest in mental health increased in Malaysia, the Philippines, and Singapore after implementing their mental health laws. On the contrary, public interest in mental health continued to decrease in Thailand despite its mental health law implementation. This can be explained by the unequal prioritization of mental health among these countries.


Bayesian Modeling of the Effects of Extreme Flooding and the Grazer Community on Algal Biomass Dynamics in a Monsoonal Taiwan Stream.
The effects of grazing and climate change on primary production have been studied widely, but seldom with mechanistic models. We used a Bayesian model to examine the effects of extreme weather and the invertebrate grazer community on epilithic algal biomass dynamics over 10 years (from January 2004 to August 2013). Algal biomass and the invertebrate grazer community were monitored in the upstream drainage of the Dajia River in Taiwan, where extreme floods have been becoming more frequent. The biomass of epilithic algae changed, both seasonally and annually, and extreme flooding changed the growth and resistance to flow detachment of the algae. Invertebrate grazing pressure changes with the structure of the invertebrate grazer community, which, in turn, is affected by the flow regime. Invertebrate grazer community structure and extreme flooding both affected the dynamics of epilithic algae, but in different ways. Awareness of the interactions between algal communities and grazers/abiotic factors can help with the design of future studies and could facilitate the development of management programs for stream ecosystems.


The effect of seed location on functional connectivity: evidence from an image-based meta-analysis.
Default mode network (DMN) is the most involved network in the study of brain development and brain diseases. Resting-state functional connectivity (rsFC) is the most used method to study DMN, but different studies are inconsistent in the selection of seed. To evaluate the effect of different seed selection on rsFC, we conducted an image-based meta-analysis (IBMA). We identified 59 coordinates of seed regions of interest (ROIs) within the default mode network (DMN) from 11 studies (retrieved from Web of Science and Pubmed) to calculate the functional connectivity; then, the uncorrected t maps were obtained from the statistical analyses. The IBMA was performed with the t maps. We demonstrate that the overlap of meta-analytic maps across different seeds' ROIs within DMN is relatively low, which cautions us to be cautious with seeds' selection. Future studies using the seed-based functional connectivity method should take the reproducibility of different seeds into account. The choice of seed may significantly affect the connectivity results.


Antibody Array as a Tool for Screening of Natural Agents in Cancer Chemoprevention.
The efficacy of a given drug resides mainly on its ability to specifically target disease mechanisms. Natural products represent the leading source of bioactive molecules with a broad range of activities. It is becoming increasingly clear that natural compounds exert their chemopreventive or antitumoral activities targeting simultaneously diverse cellular pathways. Here we describe the use of antibody array to assess the effects of natural compounds on the expression of multiple proteins and of their posttranslational modifications in cellular systems. This might turn to be a very flexible application for cancer chemoprevention studies.


Patient and clinician collaboration in the design of a national randomized breast cancer trial.
To show breast cancer patient involvement in the design of a national randomized trial of hormone replacement therapy (HRT) in symptomatic patients will increase accrual. Three stakeholder groups [(1) researchers from the Lynda Jackson Macmillan Centre, (2) the Consumers' Advisory Group for Clinical Trials (CAG-CT), (3) clinicians responsible for a pilot randomized HRT study in breast cancer patients] developed this collaborative study. (1) Nine focus group discussions were conducted to identify issues relevant to breast cancer patients about HRT and a national trial: six involved women from breast cancer support groups nationwide and three patients who had previously participated in the pilot randomized HRT study. (2) Recommendations from the focus groups (analysed by Grounded Theory) were debated by the research stakeholders and focus group representatives at a 1-day meeting and consensus reached (using a voting system) on mutual priorities for incorporation into the design of a national HRT trial. (3) Representatives from the CAG-CT and focus groups participated in subsequent national HRT steering committee meetings to ensure that these priorities were accounted for and the resulting trial design summary was circulated to the CAG-CT and all focus group representatives for comment. Focus groups demonstrated that the complexity of factors relating to trial participation was not just restricted to the research topic in question. Patient-clinician interaction provided a platform for negotiating potential conflicts over trial design and outcomes. Patient feedback suggested that mutually agreed priorities were accounted for in the trial design. Clinical research planning should involve all research stakeholders at the outset. Quantifying the impact of patient involvement in terms of trial accrual may be too simple given the complexity of their motivations for participating in trials.


Preferential association with ClC-3 permits sorting of ClC-4 into endosomal compartments.
ClC-4 is an intracellular Cl-/H+ exchanger that is highly expressed in the brain and whose dysfunction has been linked to intellectual disability and epilepsy. Here we studied the subcellular localization of human ClC-4 in heterologous expression systems. ClC-4 is retained in the endoplasmic reticulum (ER) upon overexpression in HEK293T cells. Co-expression with distinct ClC-3 splice variants targets ClC-4 to late endosome/lysosomes (ClC-3a and ClC-3b) or recycling endosome (ClC-3c). When expressed in cultured astrocytes, ClC-4 sorted to endocytic compartments in WT cells but was retained in the ER in Clcn3-/- cells. To understand the virtual absence of ER-localized ClC-4 in WT astrocytes, we performed association studies by high-resolution clear native gel electrophoresis. Although other CLC channels and transporters form stable dimers, ClC-4 was mostly observed as monomer, with ClC-3-ClC-4 heterodimers being more stable than ClC-4 homodimers. We conclude that unique oligomerization properties of ClC-4 permit regulated targeting of ClC-4 to various endosomal compartment systems via expression of different ClC-3 splice variants.


A selective analysis of sulfamethoxazole - Trimethoprim in tablet formulations using graphene oxide-zinc oxide quantum dots based nanocomposite modified glassy carbon electrode.
In this study, simultaneous analysis on electrochemical detection of SMX and TMP in tablet formulation has been made using graphene oxide (GO) and ZnO QDs (GO-ZnO QDs) based nanocomposite modified glassy carbon electrode (GCE). The functional group presence was observed using FTIR study. The electrochemical characterization for GO, ZnO QDs and GO-ZnO QDs was studied using cyclic voltammetry using [Fe(CN)6]3- medium. In order to estimate the electrochemical redox behavior of SMX and TMP from tablet, the developed electrodes GO/GCE, ZnO QDs/GCE and GO-ZnO QDs/GCE are initially tested for electrochemical activity towards the SMX tablet in BR pH 7 medium. Later their electrochemical sensing has been monitored using square wave voltammetry (SWV). On observing the characteristic behavior of developed electrodes, GO/GCE exhibited detection potential of +0.48 V for SMX and +1.37 V for TMP whereas, ZnO QDs/GCE with +0.78V for SMX and for TMP 1.01 V respectively. Similarly, for GO-ZnO QDs/GCE, its 0.45 V for SMX and 1.11 V for TMP are observed using cyclic voltammetry. The obtained potential results on detecting SMX and TMP are in good agreement with previous results. Under optimized conditions, the response has been monitored with linear concentration range 50 μg/L to 300 μg/L for GO/GCE, ZnO QDs/GCE and GO-ZnO QDs/GCE in SMX tablet formulations. Their detection limits for the individual detection using GO-ZnO/GCE for SMX and TMP are found to be 0.252 ng/L and 19.10 μg/L and for GO/GCE it was 0.252 pg/L and 2.059 ng/L respectively. It was observed that ZnO QDs/GCE could not provide the electrochemical sensing towards SMX and TMP which may be due to the ZnO QPs can act as a blocking layer impeding the electron transfer process. Thus, the sensor performance lead to promising biomedical applications in real-time monitoring on evaluating selective analysis with SMX and TMP in tablet formulations.


Evaluation of the Abbott RealTime HCV genotype II plus RUO (PLUS) assay with reference to core and NS5B sequencing.
HCV genotyping remains a critical tool for guiding initiation of therapy and selecting the most appropriate treatment regimen. Current commercial genotyping assays may have difficulty identifying 1a, 1b and genotype 6. To evaluate the concordance for identifying 1a, 1b, and genotype 6 between two methods: the PLUS assay and core/NS5B sequencing. This study included 236 plasma and serum samples previously genotyped by core/NS5B sequencing. Of these, 25 samples were also previously tested by the Abbott RealTime HCV GT II Research Use Only (RUO) assay and yielded ambiguous results. The remaining 211 samples were routine genotype 1 (n=169) and genotype 6 (n=42). Genotypes obtained from sequence data were determined using a laboratory-developed HCV sequence analysis tool and the NCBI non-redundant database. Agreement between the PLUS assay and core/NS5B sequencing for genotype 1 samples was 95.8% (162/169), with 96% (127/132) and 95% (35/37) agreement for 1a and 1b samples respectively. PLUS results agreed with core/NS5B sequencing for 83% (35/42) of unselected genotype 6 samples, with the remaining seven "not detected" by the PLUS assay. Among the 25 samples with ambiguous GT II results, 15 were concordant by PLUS and core/NS5B sequencing, nine were not detected by PLUS, and one sample had an internal control failure. The PLUS assay is an automated method that identifies 1a, 1b and genotype 6 with good agreement with gold-standard core/NS5B sequencing and can aid in the resolution of certain genotype samples with ambiguous GT II results.


Infrared light induced sustainable enhancement of photocatalytic efficiency by thermoelectric effect.
Hindering the recombination of photoinduced electron-hole pairs is of significance for enhancing photocatalytic performance. Applying a voltage to separate carriers offers an option to realize it. Thermoelectric materials own the ability to continuously sustain a voltage when a temperature difference exists between its two sides. However, maintaining the thermoelectric effect without wasting additional energy remains a challenge. Herein, a C3N4/Polyaniline/Poly(vinylidene fluoride) cilia array was fabricated to reach efficient photocatalysis through thermoelectric effect and photothermal effect. The cilia array structure offers more than 40% of light absorbance compared to the film. Hence, the infrared light in sunlight, which was usually omitted in photocatalysis, was transformed into heat. Through the unique design which draws upon the huge difference in thermal conductivity of air and water, a temperature gap was formed between the top and bottom sides of the cilia array by half-submerging it in water. Therefore, the photocatalytic efficiency was improved by 84.4%. This work achieves an energy-saving method to enhance photocatalytic performance by activating thermoelectric effect through infrared light, shedding light on the application of multi-modes enhanced photocatalysis.


Prospective comparison of in vitro normal cell radiosensitivity and normal tissue reactions in radiotherapy patients.
This pilot study was undertaken to assess the relationship between in vitro radiosensitivity of different normal cell types and the type and severity of normal tissue reactions in individual patients after radiotherapy. Twenty-one patients with head and neck cancer were studied prospectively; four with head and neck and two with breast cancer were studied retrospectively. The retrospective cases were chosen because they exhibited unusual (severe or minimal) normal tissue reactions after radiotherapy. Small skin biopsies and blood samples were obtained and used to generate in vitro fibroblast and lymphocyte cultures, respectively. Clonogenic assays were used to measure in vitro fibroblast and lymphocyte radiosensitivity after high- and low-dose rate irradiation. Head and neck patients were treated by conventional, hyperfractionated, or concomitant boost regimens, which have been found to yield an equal probability of late normal tissue reactions. The highest dose received by each normal tissue in the target volume was estimated using computed tomography treatment plans. The median patient follow-up time was 19 months (range: 13-25). The distributions of in vitro radiosensitivity parameters and the grade of tissue reaction scores in the patients showed a broad range between individuals. When in vitro parameters were compared to the acute and late tissue reactions, the radiosensitivity of fibroblasts, measured as surviving fraction at 2 Gy after high-dose rate irradiation, showed a highly significant correlation with the maximum grade of late effects (p < 0.0001 for the whole group and p = 0.0013 for the group of patients studied prospectively). No significant correlation was found between fibroblast radiosensitivity and maximum grade of acute effects or between lymphocyte radiosensitivity and either acute or late effects. We conclude that individuals vary in normal cell radiosensitivity, and that in vitro measurements of fibroblast radiosensitivity may predict the magnitude of late normal tissue reactions after radiotherapy. These preliminary results, however, need to be validated in a larger group of patients.


Dimerization of ZIP promotes its transcriptional repressive function and biological activity.
Self-association of a protein to form dimer and oligomer is a general theme in biological control mechanism, and is increasingly understood to be an important step in many cellular processes, including signaling transduction, protein degradation and transcriptional regulation. Previously, we cloned and functionally characterized a gene encoded for ZIP (zinc finger and G-patch domain-containing protein). We showed that ZIP is a novel transcription repressor that regulates, through recruitment of the nucleosome remodeling and deacetylase (NuRD) complex, a collection of functionally important genes including the epidermal growth factor receptor (EGFR) oncogene. The important role ZIP plays in controlling cell proliferation and carcinogenesis highlights the need for a detailed understanding of the finely mechanisms by which ZIP is regulated. Here, we report that ZIP forms homodimers in vitro and in vivo through its C-terminal domains. We demonstrated that ZIP dimerization promotes its transcriptional repressive activity and is essential for its DNA binding. We showed that enforced dimerization of ZIP suppresses EGFR expression, leading to the delay of cell cycle progression and the inhibition of breast cancer cell proliferation. Thus, our results revealed that dimerization is crucial for is transcriptional repressive function and biological activity and provided a finely tuned means for the regulation the expression of EGFR oncogene. These may shed new light on the EGFR-related breast carcinogenesis and offer a potential new target for breast cancer therapy.


A comparative study of black-box and white-box data-driven methods to predict landfill leachate permeability.
Due to the dynamic and complexity of leachate percolation within municipal solid waste (MSW), planning and operation of solid waste management systems are challenging for decision-makers. In this regard, data-driven methods can be considered robust approaches to modeling this problem. In this paper, three black-box data-driven models, including artificial neural networks (ANN), adaptive neuro-fuzzy inference systems (ANFIS), and support vector regression (SVR), and also three white-box data-driven models, including the M5 model tree (M5MT), classification and regression trees (CART), and group method of data handling (GMDH), were developed for modeling and predicting landfill leachate permeability ([Formula: see text]). Based on a previous study conducted by Ghasemi et al. (2021), [Formula: see text] can be formulated as a function of impermeable sheets ([Formula: see text]) and copper pipes ([Formula: see text]). Hence, in the present study, [Formula: see text] and [Formula: see text] were adopted as input variables for the prediction of [Formula: see text] and evaluated for the performance of the suggested black-box and white-box data-driven models. Scatter plots and statistical indices such as coefficient of determination (R2), root mean square error (RMSE), and mean absolute error (MAE) were used for qualitative and quantitative evaluations of the effectiveness of the suggested methods. The outcomes indicated all of the provided models successfully predicted [Formula: see text]. However, ANN and GMDH had higher accuracy between the proposed black-box and white-box data-driven models. ANN with R2 = 0.939, RMSE = 0.056, and MAE = 0.017 was marginally better than GMDH with R2 = 0.857, RMSE = 0.064, and MAE = 0.026 in the testing stage. Nevertheless, an explicit mathematical expression provided by GMDH to predict k was easier and more understandable than ANN.


General Gel-sol Method to Synthesize Various Highly Fluorescent Nanoclusters and Assay of Nuclease with the Near Infrared-emitting Gold Nanoclusters.
A general egg white gel-sol strategy for fabrication of highly fluorescent Au, Ag, Cu, and Pt nanoclusters (NCs) and the first example of using Au NCs for assay of nuclease activity and inhibition were described. The Au NCs enabled bright red fluorescence, and the other Ag, Cu, and Pt NCs have highly blue emission. The red-emitting Au NCs were further applied in assay of S1 nuclease activity and inhibition. Free hemin efficiently quenches the emission of Au NCs by photoinduced electron transfer due to the formation of Au NCs-hemin conjugates. However, G-quadruplex/hemin exerts negligible effect on its fluorescence due to no Au NCs-hemin conjugate formed. There are stronger electrostatic repulsion effects between both negatively charged G-quadruplex and Au NCs. Therefore, a novel G-quadruplex/hemin-based Au NCs fluorescent sensor for S1 nuclease was designed. A known G-rich oligonucleotide (ODN) serves as not only substrate for S1 nuclease but also for the construction of G-quadruplex/hemin. The G-rich ODN is hydrolyzed into fragments by S1 nuclease resulting in no G-quadruplex/hemin formation. Therefore, the free hemin quenches Au NCs fluorescence remarkably and the assay of S1 nuclease activity and inhibition has accomplished. Both the fluorescent NCs syntheses and the detection of S1 nuclease are facile and efficient.


A Workflow for the Identification of Mycotoxin Metabolites Using Liquid Chromatography-Ion Mobility-Mass Spectrometry.
The structural identification of phase-I and phase-II metabolites of mycotoxins is a difficult task, mostly due to the lack of standards and because of the large number of isomeric forms. Here, we describe the use of ion mobility-mass spectrometry to analyze cereal extracts and how structural information on newly discovered mycotoxins metabolites could be obtained.


Detection of Bacterial Neutral Ceramidase in Diabetic Foot Ulcers with an Optimized Substrate and Chemoenzymatic Probes.
Ceramidases (CDases) are important in controlling skin barrier integrity by regulating ceramide composition and affording downstream signal molecules. While the functions of epidermal CDases are known, roles of neutral CDases secreted by skin-residing microbes are undefined. Here, we developed a one-step fluorogenic substrate, S-B, for specific detection of bacterial CDase activity and inhibitor screening. We identified a non-hydrolyzable substrate mimic, C6, as the best hit. Based on C6, we designed a photoaffinity probe, JX-1, which efficiently detects bacterial CDases. Using JX-1, we identified endogenous low-abundance PaCDase in a P. aeruginosa monoculture and in a mixed skin bacteria culture. Harnessing both S-B and JX-1, we found that CDase activity positively correlates with the relative abundance of P. aeruginosa and is negatively associated with wound area reduction in clinical diabetic foot ulcer patient samples. Overall, our study demonstrates that bacterial CDases are important regulators of skin ceramides and potentially play a role in wound healing.


Facile synthesis of multifunctional C@Fe3O4-MoO3-rGO ternary composite and its versatile roles as sonoadsorbent to ameliorate triphenylmethane textile dye and as potential electrode for supercapacitor applications.
The toxic wastewater effluents from textile dyes have been a significant environmental threat worldwide in recent decades. Against this backdrop, this study investigates the performance of C@Fe3O4-MoO3-rGO as a sonoadsorbent to ameliorate crystal violet (CV) dye from the aqua matrix and further explores its potential as an electrode in supercapacitor applications. The phase purity, crystal structure, surface morphology, thermal stability and magnetic behaviour characteristics of the composite were studied using various characterisation techniques such as powder X-ray diffraction (XRD), Raman Spectroscopy, Fourier transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (FESEM), High-resolution transmission electron microscopy (HRTEM), Thermogravimetric analysis (TGA) and Vibrating-sample magnetometry (VSM). From the Langmuir isotherm model, the synthesised sonoadsorbent exhibited a maximum adsorption capacity of 1664.26 mg/g for crystal violet, which is remarkably high. Further, to its inherited magnetic characteristics, the composite can be easily separated from the solution by using an external magnet. Furthermore, the working electrode was synthesised with 80% active material, 10% carbon black, and 10% polyvinylidene difluoride to investigate its suitability in supercapacitor applications. The C@Fe3O4-MoO3-rGO composite exhibited an excellent capacitance value of 180.36 F/g with commendable cycling stability, making it suitable as a potential cathode material for the next generation supercapacitors.


Production and properties of crude enterotoxin of Pseudomonas aeruginosa.
Pseudomonas aeruginosa CTM-3 was found to be the most potentially enterotoxigenic strain out of the 12 isolates recovered from milk, as a high fluid length ratio, i.e. F/L (1.1) in rabbit gut and a strong permeability response in rabbit skin (38.5 mm2 necrotic zone) was obtained with this culture. No clear-cut relationship between the two tests was observed. Six of the ethidium bromide (300 micrograms/ml) cured variants of this culture completely lost their ability to produce enterotoxin indicating the possible involvement of a plasmid in enterotoxin synthesis. The crude enterotoxin from P. aeruginosa CTM-3 was completely inactivated in 15 s at 72 degrees C. However, it was fairly stable at pH values in the range 4.5-7.5. Both pepsin and trypsin inactivated the enterotoxin activity at a concentration of 40 micrograms/ml. Organic acids, formalin and hydrogen peroxide had no significant effect on the enterotoxin activity. The need for further investigations with purified preparations is emphasized.


Headache temporal patterns: towards a chronobiological model.
Rhythmical changes in terrain susceptibility and trigger occurrence can induce periodic temporal patterns in headache patients, with readily foreseeable frequency cycles of attacks. The impaired ability of biological functions to adjust to cyclic environmental changes represents the minus, the handicap, the increased risk of clinical symptomatology (headache); attacks occur when the precarious systems of these patients are forced by cyclical environmental stimuli towards phase shiftings or to cope with new levels of performance. A dyschronic hypothesis of primary headache must be based upon observations demonstrating that along with dysfunctions of the pain control systems there is also a vulnerability of the rhythmic physiological organization of CNS.


Video-assisted thoracoscopy for the diagnosis of mediastinal masses in children.
Video-assisted thoracoscopy has been successfully used for several different thoracic procedures in adults. However, its use in children has been limited. The present study evaluated our experience with video-assisted thoracoscopy in the diagnosis of mediastinal masses in children. Nine children (age range, 3 to 18 years) with undiagnosed mediastinal masses underwent video-assisted thoracoscopy. The operation was performed using general anesthesia, with the patient intubated with a single lumen endotracheal tube. In all cases adequate tissue for diagnosis was obtained. Three patients had tuberculosis, two had Hodgkin's disease, two had granuloma, one had metastatic Wilms' tumor, and one had thymic hyperplasia. There were no complications related to the operative procedure. Video-assisted thoracoscopy for the diagnosis of mediastinal masses in children is a safe procedure. It provides good visualization, access to the mediastinum and adequate tissue for diagnosis. Further, postoperative discomfort is tolerable and cosmetic results are excellent.


The influence of the cost of growth on ectotherm metabolism.
A new model of ectothermic growth and metabolism is proposed. This model differs from most earlier models in representing explicitly the contribution of the "cost of growth" to ectotherm metabolism. It is shown that the cost of growth may constitute between 17 and 29% of the metabolism of an "average" ectotherm population. Furthermore, the metabolism of an "average" growing ectotherm may be between 40 and 79% greater than that of a non-growing ectotherm. As many environmental factors induce changes in metabolic rates of this magnitude, it is suggested that many factors which cause changes in metabolic rates do so indirectly by altering growth rates. In particular, it is suggested that body size, food availability and temperature often indirectly influence metabolic rates through their effects on growth rates, rather than by directly determining metabolic rates as has usually been assumed.


[The clinico-morphological parallels in diffuse connective tissue diseases].
The authors present an investigation of the clinical and morphological signs and symptoms of diffuse diseases of the connective tissue in 27 of 50 examined patients. For verification of connective tissue disease it is recommended to carry out early histological examination of the biopsy specimens. The biopsy material should be adequately taken with consideration of the area and depth of involved tissue.


An Electromyography-Based Constitutive Law for Force Generation in Skeletal Muscle-Part II: Model Validation on the Ankle Joint Complex.
Part II of this study evaluates the predictive ability of the skeletal muscle force model derived in Part I within the ankle joint complex. The model is founded in dimensional analysis and uses electromyography and the muscle force-length, force-velocity, and force-frequency curves as inputs. Seventeen subjects (eight males, nine females) performed five different exercises geared toward activating the primary muscles crossing the ankle joint. Motion capture, force plate, and electromyography data were collected during these exercises for use in the analysis. A constant, Km, was calculated for each muscle of each subject using four of the five exercises. The fifth exercise was then used to validate the results by treating the moments due to muscle forces as known and all other components in Euler's second law as unknown. While muscle forces cannot be directly validated in vivo, methods can be developed to test these values with reasonable confidence. This study compared moments about the ankle joint due to the calculated muscle forces to the sum of the moments due to all other sources and the kinematic terms in the second Newton-Euler equation of rigid body motion. Average percent errors for each subject ranged from 4.2% to 15.5% with a total average percent error across all subjects of 8.2%, while maximum percent errors for each subject ranged from 33.3% to 78.0% with an overall average maximum of 52.4%. Future work will examine sensitivity analyses to identify any potential simplifications to the model and solution process, as well as validate the model on a more complex joint system to ensure it still performs at a satisfactory level.


Human somatosensory evoked magnetic fields to vibratory stimulation of the index finger: is there frequency organization in SI?
Frequency organization in the human somatosensory cortex was studied. Somatosensory evoked magnetic fields (SEFs) from 12 subjects were measured following vibratory stimulation of the index finger by using a 122 channel whole head SQUID system. Sensory stimuli comprising a 40 ms vibration at frequencies of 50, 100, 200 and 400 Hz were delivered to the volar surface of the tip of the right index finger. Using a single dipole model, the sources of the magnetic fields were estimated and mapped onto magnetic resonance images of each subject. The analysis of variance test (ANOVA) was used for statistics. Source localization was determined on the main two peaks (M60 and M110) of the SEFs. All of the sources were located in the area 3b of somatosensory cortex (SI). There were no statistically significant differences between the locations of the dipoles evoked by different frequency stimulations. These results demonstrate the absence of systematic frequency organization at the hand representation area of the SI cortex. We speculate that high frequency vibration above 100 Hz are coded by the fast-spiking interneurons which synapse with Pacinian pyramidal neurons in SI.


Cytotoxic drug treatment of reactive amyloidosis in rheumatoid arthritis with special reference to renal insufficiency.
Twenty-two patients with amyloidosis secondary to rheumatoid arthritis were randomised and followed prospectively in order to determine whether treatment with cytotoxic drugs could postpone the development of end-stage renal failure. The diagnosis of amyloidosis was based on albuminuria, amyloid-positive rectal and/or abdominal fat aspiration and/or renal biopsies. Renal function was followed by repeated 51Cr-EDTA measurements of the glomerular filtration rate (GFR). Urinary albumin and serum-creatinine were found unreliable as predictors of renal function. GFR declined more rapidly in the patient group receiving only symptomatic drugs and no cytotoxic drugs (NT-group). After an initial decline, the GFR in the cytotoxic drug treatment group (T-group), mean treatment quotient 79%, levelled off and remained constant for a considerable time. The mean observation time was 45.7 months in the NT-group and 53.5 months in the T-group. Seven out of eleven patients in the NT-group developed end-stage renal disease, compared to two out of eleven patients in the T-group. The cumulative proportion of survivors in the NT-group at 36 and 60 months was 71% and 27% respectively. The corresponding figures in the T-group were 89% and 89%. The difference in favour of the cytotoxic drug-treated group was significant (p less than 0.04).


Management of hydrocephalus around the world.
The objective of this study is to review the management of hydrocephalus and, in particular, how different economic and social conditions affect its treatment around the world. The main techniques for the surgical treatment and the management of hydrocephalus have been retraced through a brief historical overview up to the present day. During the last century, continuous technological progress has favored the diffusion of expensive and sophisticated shunt systems. On the other hand, the advent of minimally invasive endoscopic techniques, such as endoscopic third ventriculostomy, seems to represent a valid route for attempting a natural cerebrospinal fluid diversion, thus avoiding complications related to shunt failure. The management of hydrocephalus around the world is still widely debated. However, definition of proper indications and adequate training in neuroendoscopic techniques seem to represent the preeminent trend for new generations of neurosurgeons.


Automatic delineation algorithm of reference region for amyloid imaging based on kinetics.
This study aims to develop an algorithm named AutoRef to delineate a reference region for quantitative PET amyloid imaging. AutoRef sets the reference region automatically using a distinguishing feature in the kinetics of reference region. This is reflected in the shapes of the tissue time activity curve. A statistical shape recognition algorithm of the gaussian mixture model is applied with considering spatial and temporal information on a reference region. We evaluate the BPND with manually set reference region and AutoRef using 86 cases (43 positive cases, 10 equivocal cases, and 33 negative cases) of dynamically scanned 11C-Pittsburgh Compound-B. From the Bland-Altman plot, the difference between two BPND is 0.099 ± 0.21 as standard deviation, and no significant systematic error is observed between the BPND with AutoRef and with manual definition of a reference region. Although a proportional error is detected, it is smaller than the 95% limits of agreement. Therefore, the proportional error is negligibly small. AutoRef presents the same performance as the manual definition of the reference region. Further, since AutoRef is more algorithmic than the ordinary manual definition of the reference region, there are few operator-oriented uncertainties in AutoRef. We thus conclude that AutoRef can be applied as an automatic delineating algorithm for the reference region in amyloid imaging.


Ejaculate-hormonal traits in the leopard cat (Felis bengalensis) and sperm function as measured by in vitro penetration of zona-free hamster ova and zona-intact domestic cat oocytes.
Electroejaculate traits and circulating follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone concentrations were analyzed in adult leopard cats (Felis bengalensis), a rare felid species indigenous to east Asia. The ability of leopard cat sperm to bind and penetrate zona-free hamster ova and zona-intact domestic cat oocytes in vitro was examined as a means of testing sperm function. The influence of culture media [Biggers, Whitten, Whittingham (BWW) vs. modified Krebs Ringer bicarbonate (mKRB)], seminal plasma removal, and swim-up separation on sperm motility, sperm morphology, and oocyte penetration also were assessed. Sperm treatments included dilution of raw semen (DR), ejaculate centrifugation, and either resuspension (NS) or swim-up processing (SU). The percentage of oocytes penetrated (penetration rate) and the number of penetrated sperm/oocyte (penetration index) were determined. Ejaculates from each male consisted of at least a 50% sperm motility rating, and hormone concentrations in individual males were unrelated to any ejaculate trait measured concurrently on the same day. The SU technique improved (P less than 0.05) percent sperm motility and the proportion of structurally normal sperm compared to DR and NS treatments. Leopard cat spermatozoa were capable of binding to and penetrating hamster ova and domestic cat oocytes; however, penetration was influenced by culture medium and seminal processing. In the hamster assay, a higher (P less than 0.05) penetration rate and penetration index were achieved when mKRB was used for gamete incubation instead of BWW. NS processing also increased (P less than 0.05) overall penetration compared to DR and SU. In the cat oocyte assay, zona penetration rate was similar (P greater than 0.05) in the DR, NS, and SU aliquots; however, the zona penetration index was increased (P less than 0.05) by the NS compared to the DR and SU treatments. This study 1) provides baseline ejaculate and endocrine norms for the leopard cat, 2) demonstrates that leopard cat sperm undergo nuclear decondensation in hamster ova and penetrate zona-intact domestic cat oocytes, 3) indicates that seminal plasma removal enhances leopard cat sperm fertilizing ability and ovum penetration, and 4) suggests that heterologous oocyte penetration is effective for assessing factors influencing fertilization and sperm function in this nondomestic felid.


Early gut microbiological changes and metabolomic changes in patients with sepsis: a preliminary study.
The gut microbiota is closely related to the development of sepsis. The aim of this study was to explore changes in the gut microbiota and gut metabolism, as well as potential relationships between the gut microbiota and environmental factors in the early stages of sepsis. Fecal samples were collected from 10 septic patients on the first and third days following diagnosis in this study. The results showed that in the early stages of sepsis, the gut microbiota is dominated by microorganisms that are tightly associated with inflammation, such as Escherichia-Shigella, Enterococcus, Enterobacteriaceae, and Streptococcus. On sepsis day 3 compared to day 1, there was a significant decrease in Lactobacillus and Bacteroides and a significant increase in Enterobacteriaceae, Streptococcus, and Parabacteroides. Culturomica_massiliensis, Prevotella_7 spp., Prevotellaceae, and Pediococcus showed significant differences in abundance on sepsis day 1, but not on sepsis day 3. Additionally, 2-keto-isovaleric acid 1 and 4-hydroxy-6-methyl-2-pyrone metabolites significantly increased on sepsis day 3 compared to day 1. Prevotella_7 spp. was positively correlated with phosphate and negatively correlated with 2-keto-isovaleric acid 1 and 3-hydroxypropionic acid 1, while Prevotella_9 spp. was positively correlated with sequential organ failure assessment score, procalcitonin and intensive care unit stay time. In conclusion, the gut microbiota and metabolites are altered during sepsis, with some beneficial microorganisms decreasing and some pathogenic microorganisms increasing. Furthermore, Prevotellaceae members may play different roles in the intestinal tract, with Prevotella_7 spp. potentially possessing beneficial health properties and Prevotella_9 spp. potentially playing a promoting role in sepsis.


Role of 18F-FDG PET/CT in Guiding Surgical Management of Clinically Node Negative Neck (cN0) in Carcinoma Oral Cavity.
Conventional staging paradigm with clinical examination or imaging invariably leads to underestimation of occult metastatic neck disease in oral cavity carcinoma. The advantage of 18F-FDG PET/CT is in its ability to identify lymph nodes without morphological changes yet harboring occult metastases. We present findings of our study to evaluate diagnostic accuracy of 18F-FDG PET/CT, in detecting occult cervical lymph node metastasis in carcinoma oral cavity. In a single institution prospective study, 51 consecutive patients with histologically proven (cT1/T2) oral cavity carcinoma and clinically node negative neck (cNo), underwent 18F-FDG PET/CT before elective neck dissection of 58 neck sides. 18F-FDG PET/CT findings were compared with histopathology of dissected nodes, to calculate diagnostic accuracy. 18F-FDG PET/CT correctly characterized the occult lymph node metastasis status (true positive + true negative) in 51 of 58 neck sides, yielding diagnostic accuracy of 87.93%. Sensitivity of 18F-FDG PET/CT was 90% and specificity was 87.5%. While a positive 18F-FDG PET/CT accurately predicted the disease in only 60% (positive predictive value), a negative 18F-FDG PET/CT reasonably ruled out occult metastases in 97.67% (negative predictive value). If a decision regarding the need for neck dissection had been based solely on 18F-FDG PET/CT, the number of neck dissections would have been reduced by 74.13%. Based on diagnostic accuracy and high negative predictive value, incorporating 18F-FDG PET/CT in preoperative staging paradigm of cT1/T2 carcinoma oral cavity will guide in selection of patients in which cN0 neck can be safely observed.


AMPKα promotes basal autophagy induction in Dictyostelium discoideum.
Autophagy is a degradation process, wherein long-lived proteins, damaged organelles, and protein aggregates are degraded to maintain cellular homeostasis. Upon starvation, 5'-AMP-activated protein kinase (AMPK) initiates autophagy. We show that ampkα- cells exhibit 50% reduction in pinocytosis and display defective phagocytosis. Re-expression of AMPKα in ampkα- cells co-localizes with red fluorescence protein-tagged bacteria. The ampkα- cells show reduced cell survival and autophagic flux under basal and starvation conditions. Co-immunoprecipitation studies show conservation of the AMPK-ATG1 axis in basal autophagy. Computational analyses suggest that the N-terminal region of DdATG1 is amenable for interaction with AMPK. Furthermore, β-actin was found to be a novel interacting partner of AMPK, attributed to the alteration in macropinocytosis and phagocytosis in the absence of AMPK. Additionally, ampkα- cells exhibit enhanced poly-ubiquitinated protein levels and allied large ubiquitin-positive protein aggregates. Our findings suggest that AMPK provides links among pinocytosis, phagocytosis, autophagy, and is a requisite for basal autophagy in Dictyostelium.


Effects of a new synthetic zerumbone pendant derivative (ZPD) on apoptosis induction and anti-migratory effects in human cervical cancer cells.
A newly synthesised zerumbone pendant derivative (ZPD) was studied in human cervical cancer cells (HeLa) for its anticancer properties. ZPD significantly inhibited the growth of human cervical cancer cells with a GI50 value of 6.35 ± 1.30 μM, which also induced morphological changes and apoptosis in a dose-dependent manner. Our data indicated that ZPD actively encouraged programmed cell death in HeLa cells which were confirmed by DNA fragmentation, phosphatidylserine translocation, increased activity of caspase 3, upregulation of the expression of the pro-apoptotic protein Bax, cleaved PARP, cleaved caspase 3 and downregulation of anti-apoptotic protein Bcl-2. ZPD also inhibited cell migration of HeLa cells, decreasing the production of MMP-2,-9 and downregulation of expression of MMPs and pro-angiogenic factor VEGF. Also it is nontoxic to normal rat cardiac myoblasts. Overall, ZPD is a promising candidate for inducing cytotoxicity, apoptosis and anti-migratory effects in cervical cancer cells.


The stimuli-responsive multiphase behavior of core-shell nanogels with opposite charges and their potential application in in situ gelling system.
Concentrated p(N-isopropylacrylamide) (PNIPAM) nanogel dispersions exhibited rich temperature-sensitive sol-gel phase transition behavior. In the present work, the influence of electrostatic forces between nanogel particles, including attraction and repulsion, on the sol-gel phase transition behavior of PNIPAM nanogel dispersions has been studied. Both oppositely charged nanogels with core-shell structures (NIA and PND nanogels) were synthesized, and their shell charges were calculated to -0.33 and 0.082 mmol/g by potentiometric titration method. When mixed with various ratio of negative and positive charge (NC value), the resultant mixture dispersions of NIA and PND nanogel (OCNs) exhibited different aggregating behavior from NIA and PND nanogels. OCN-e aggregates (NC value=1/4), which exhibited temperature-independence of electric neutrality, had the maximum size, about 1.9-2.2 times larger than NIA or PND nanogels. Concentrated OCN-e dispersions exhibited stronger ability to form shrunken gel. Its CGC was about 2.0 wt%, 4-times lower than that of NIA and PND nanogels (about 8.0 wt%). In vitro and in vivo gelling results indicated that OCN-e aggregates could form free-standing gel with good mechanical strength, and were promising to be developed as new in situ gelling system.


Partial purification and characterization of Aspergillus niger inulinase produced from sugar-beet molasses in the shaking incubator and stirred-tank bioreactors.
The objectives of this study were to purify Aspergillus niger inulinase produced from sugar-beet molasses in the shaking incubator (100 mL) and stirred-tank bioreactors (5-L and 30-L) by using some downstream processes and to determine enzyme kinetics and characterization. The results showed that the best centrifuge-time combination was 16,873 ×g-5 min with the purification coefficient of 1.4. Besides, with the ultrafiltration process, the inulinase activities yielded using the shaking incubator, pH-controlled/uncontrolled small-scale bioreactors, and large-scale bioreactor were increased from 1101.3, 2079.2, 1561.3, and 787.5 U/mL to 12,065.2, 21,789.0, 11,296.9, and 2948.1 U/mL with purification coefficients of 5.33, 1.38, 1.46, and 1.67, respectively. Additionally, for the inulinase from shaking incubator and pH-uncontrolled bioreactor, the values of Km for inulin and sucrose were 17.8 and 49.4 mg/mL and 28.8 and 25.9 mg/mL, respectively. As the enzyme amount added to the substrate increased, the activity also increased. Mn2+ is the activator of the enzyme, and Cu2+ and Ag+ are inhibitors of the enzyme. The molecular weight of inulinase has been determined to be between 60 and 70 kDa. Consequently, this study ensures valuable and significant information about the purification and characterization of inulinase for industrial implementations.


[Stress analysis of the mandible by 3D FEA in normal human being under three loading conditions].
The condition and character of stress distribution in the mandibular in normal human being during centric, protrusive, laterotrusive occlusion were analysed. The three-dimensional finite element model of the mandibular was developed by helica CT scanning and CAD/CAM software, and three-dimensional finite element stress analysis was done by ANSYS software. Three-dimensional finite element model of the mandibular was generated. Under these three occlusal conditions, the stress of various regions in the mandible were distributed unequally, and the stress feature was different;while the stress of corresponding region in bilateral mandibular was in symmetric distribution. The stress value of condyle neck, the posterior surface of coronoid process and mandibular angle were high. The material properties of mandible were closely correlated to the value of stress. Stress distribution were similar according to the three different loading patterns, but had different effects on TMJ joint. The concentrated areas of stress were in the condyle neck, the posterior surface of coronoid process and mandibular angle.


Ureteroscopic treatment of ureteral lithiasis with pneumatic lithotripsy: analysis of 287 procedures in a public hospital.
Ureteroscopes and different lithotripsy methods have greatly improved the urologist's ability to treat ureteral stones, regardless of their location in the ureter. We retrospectively reviewed our experience with ureteroscopic pneumatic lithotriptor in 287 patients with ureteral calculi. Ureteroscopic stone treatment was performed between October 1999 and May 2004. Of 221 patients with distal ureteral calculi, 209 (group 1), and 58 of 66 patients with upper ureteral calculi (group 2) were treated successfully by ureteroscopy alone. In group 1, seven migrated stones (to the upper urinary tract) were successfully treated by ESWL later. There were five-treatment failures due to ureteral perforation which consequently required open ureterolithotomy. In group 2, there were five patients with migrated stones; two of them were sent to a percutaneous nephrolithotomy center because of previously unsuccessful ESWL attempts. Three of these with migrated stones were treated by ESWL later. In three patients, we switched to open ureterolithotomy because of ureteral rupture that required surgical repair. Ureteroscopic pneumatic lithotripsy is a safe and effective treatment modality for ureteral calculi.


DIAGNOSIS OF ENDOCRINE DISEASE: High-yield thyroid fine-needle aspiration cytology: an update focused on ancillary techniques improving its accuracy.
Thyroid fine-needle aspiration (FNA) cytology is a fast growing field. One of the most developing areas is represented by molecular tests applied to cytological material. Patients that could benefit the most from these tests are those that have been diagnosed as 'indeterminate' on FNA. They could be better stratified in terms of malignancy risk and thus oriented with more confidence to the appropriate management. Taking in to consideration the need to improve and keep high the yield of thyroid FNA, professionals from various fields (i.e. molecular biologists, endocrinologists, nuclear medicine physicians and radiologists) are refining and fine-tuning their diagnostic instruments. In particular, all these developments aim at increasing the negative predictive value of FNA to improve the selection of patients for diagnostic surgery. These advances involve terminology, the application of next-generation sequencing to thyroid FNA, the use of immunocyto- and histo-chemistry, the development of new sampling techniques and the increasing use of nuclear medicine as well as molecular imaging in the management of patients with a thyroid nodule. Herein, we review the recent advances in thyroid FNA cytology that could be of interest to the 'thyroid-care' community, with particular focus on the indeterminate diagnostic category.


[New drugs--chemical, pharmacological, metabolical, analytical and legal aspects].
The characterisation of new psychoactive drugs which were identified in the last years in continuously increasing numbers is a challenge for different academic institutions. This paper gives an overview on new psychoactive drugs in regard of their chemistry, pharmacology, metabolism, analytics and legal aspects in Germany.


Susceptibility of selected winter wheat cultivars produced in Poland to Fusarium head blight.
The susceptibility of six winter wheat cultivars toFusarium head blight has beenstudied. The lowest infected plants intensity, mean degree of head damage and fusariosis index exhibited cultivar Grana which also cumulated the lowest amount of trichothecenes (DON and derivatives ). Possibility to produce NIV by Polish strains has been found.in F.graminearum.


Campylobacter fetus subspecies venerealis meningitis associated with a companion dog in a young adult: a case report.
Campylobacter spp., common commensals in the gastrointestinal tract of animals, especially poultry, can cause acute gastrointestinal illness in humans through animal-to-human transmission. Although Campylobacter fetus, especially subspecies fetus, rarely leads to systemic infections such as bacteremia in immunocompromised patients, it is unclear whether Campylobacter fetus subspecies venerealis (Cfv) causes infectious diseases in humans. A 28-year-old man with a history of chronic alcoholism visited the emergency department with weakness of the left extremities. The patient was clinically diagnosed with community-acquired bacterial meningitis. The organism from the blood culture was subsequently identified as Campylobacter fetus. On phylogenetic analysis, the 16S rRNA sequence showed 99.93% similarity with other Cfv 16S rRNA sequences. The patient had no exposure to identifiable sources except for close contact with a companion dog, which could have been a possible source of transmission. This case suggests that Cfv could lead to human systemic infections such as meningitis and that companion animals, in addition to well-known animal hosts, could be sources of transmission.