Inhibition of invasion and metastasis by glypican-3 in a syngeneic breast cancer model.
Glypican-3 (GPC3), a proteoglycan bound to the cell membrane through a GPI anchor, is widely expressed in the embryo but down regulated in most adult tissues, with some exceptions as mammary cells. GPC3 is involved in the regulation of cell proliferation and survival in specific cell types. LM3, a murine mammary tumor cell line unable to express GPC3, was stably transfected with the rat GPC3 gene to analyze its role in tumor progression. Upon injection into syngeneic BALB/c mice LM3-GPC3 clones showed less local invasiveness and developed fewer spontaneous and experimental lung metastasis than controls. GPC3-expressing cells were more sensitive to apoptosis induced by serum depletion, exhibited a delay in the first steps of spreading and were less motile than controls. On the other hand, LM3-GPC3 cells were significantly more adherent to FN than control ones. We observed that GPC3 transfectants presented a higher expression of E-cadherin and beta-catenin, molecules whose down regulation has been associated with tumor progression. Exogenous TGF-beta increased MMP-9 activity in both control and GPC3-expressing cells, but did not modulate MMP-2. Contrarily, GPC3 expression prevented the increase of MMP-2 activity induced by IGF-II. Our results suggest that GPC3 has a protective role against mammary cancer progression.


Left ventriculotomy of the heart: tissue repair and localization of collagen types I, II, III, IV, V, VI and fibronectin.
The reparative process following left ventriculotomy was investigated immunohistochemically using anti-type I, II, III, IV, V and VI collagen antibodies, and anti-fibronectin antibody. Wound healing began with proliferation of young fibroblasts positive for type I, III and V collagens at the wound margin; vascular granulation tissue then grew into the injured myocardium followed by deposition of fibrous components immunoreactive with type I and III. At 30 days after operation when almost the entire thickness of the myocardium at the wound was replaced by fibrosing granulation tissue, a small cluster of adipocytes appeared around capillaries at the wound margin. The granulation tissue was gradually replaced by the adipose tissue with establishment of a fibrous union at the subendocardium by 90 days. In addition to type I and III collagens, type VI collagen was detected in a fine fibrillary pattern along thick collagen fibre bundles in the fibrous tissue and around the adipocytes. Fibronectin was distributed diffusely in the granulation tissue and gradually decreased with increase of the fibrous components. These results indicate that the ventriculotomy was finally repaired in the form of a fibrous scar, particularly in the endocardium. There was marked infiltration of adipose tissue in the damaged myocardium. Presumably type VI collagen, as well as type I and type III collagens, plays an important role in wound union.


Mastectomy with one-stage or two-stage reconstruction in breast cancer: analysis of early outcomes and patient's satisfaction.
Aim of this study is to compare early post-operative outcomes and patient's satisfaction after skin-sparing and/or nipple-sparing mastectomy (SSM/SNSM) followed either by breast reconstruction with one-stage prepectoral implantation or two-stage technique for breast cancer (BC) or BRCA1/2 mutation.From January 2018 to December 2021, 96 patients (mean age of 51.12 ± 10.9) underwent SSM/SNSM and were divided into two groups: in group A (65 patients, 67.7%), mastectomy was followed by one-stage reconstruction; in group B (31 patients, 32.3%) by two-stage. Operative time was significantly longer in A vs. B (307.6 ± 95.7 vs. 254.4 ± 90.91; P < 0.05). Previous breast surgery was more common in B vs. A (29.0% vs. 7.7%; P < 0.05), while bilateral surgery was performed more frequently in A vs. B (40% vs. 6.5%; P = 0.001). All SSM/SNSM for BRCA1/2 mutation were followed by immediate prepectoral implantation. No significant differences were found between groups in terms of post-operative complications. At pathology, DCIS and invasive ST forms, such as multicentric/multifocal forms, were detected more frequently in B, while NST type in A (all P < 0.05). A multivariate analysis showed improved post-operative satisfaction at BREAST-Q survey in Group A (P = 0.001). Encouraging oncologic outcomes after SSM/SNSM for BC enabled the improvement of breast reconstructive techniques. One-stage reconstruction is characterized by better aesthetic outcomes and by greater patient's satisfaction. When SSM/SNSM is technically difficult to perform, as in multicentric/multifocal forms or previous breast surgery, mastectomy followed by two-stage reconstruction should be considered to achieve a radical surgery.


Corticosteroid resistance in chronic obstructive pulmonary disease: inactivation of histone deacetylase.
By contrast with patients with asthma, those with chronic obstructive pulmonary disease (COPD) are poorly responsive to the anti-inflammatory actions of corticosteroids, and these drugs provide little clinical benefit. In both diseases, multiple inflammatory genes are activated, which results from acetylation of core histones around which DNA is wound. This acetylation opens up the chromatin structure allowing gene transcription and synthesis of inflammatory proteins to proceed. Corticosteroids recruit histone deacetylase 2 (HDAC2) to the actively transcribing gene, which reverses this process and switches off inflammatory gene transcription. We propose that in patients with COPD, HDAC2 function is impaired by cigarette smoking and oxidative stress, leading to a pronounced reduction in responsiveness to corticosteroids. Oxidative stress could generate peroxynitrite, which impairs HDAC2 activity through nitration of critical tyrosine residues. This hypothesis raises the possibility that novel therapeutic approaches might unlock this corticosteroid resistance, leading to more effective anti-inflammatory treatments for COPD and other severe inflammatory diseases.


Two-sample Kolmogorov-Smirnov test for truncated data.
A nonparametric statistical test to compare two cumulative frequency distribution functions is presented that can be used even when both samples include censored data, as is often the case when comparing the survival of two groups of laboratory animals under conditions in which the experiment is terminated before all the animals die. (Such a design can produce considerable savings and is to be recommended.) The program calculates exact probabilities for both the one-sided and two-sided alternatives to the null hypothesis, applicable to the case of equal group size, as well as the corresponding general asymptotic values; a continuity correction is employed that markedly improves the asymptotic approximation. Expressions are stated in terms of two different but related statistics, and the one that utilizes more information in any particular set of data is selected for the probability calculations. All basic equations and definitions are provided.


Formalization of a new stock trend prediction methodology based on the sector price book value for the Colombian market.
As a financial indicator, Tobin's Q is related to making investment decisions based on the organization's market value related to the organization's replacement costs. The purpose of this study is to develop a methodology for predicting the trend of stock value based on the relationship between the fluctuation of Tobin's Q by sector as a trend index and the stock price variation of the Columbia stock market. To this end, a quantitative quasi-experimental survey will be conducted on shares traded by December 30, 2019. This is at least 90% of the time we have traded in the last 5 years. From the average Q value of the relevant economic sector, the value of each company's stock is adjusted to calculate the estimated price of the company's stock. If there is a disparity between the estimated value of the stock and the value at time t, you can forecast the stock price transition. If the computation yields a more significant result than what is now witnessed in the market, the next period's development will be positive; if it yields a lower result, its development will be negative. The results allow us to establish a significant influence of industry results on the performance of corporate Tobin's Q at the individual level. The significance level is greater than 50% in all cases, and profitability does not go below 30% in any sector, even reaching 100%. The methodology used in this study is essential to all investors tiny firms because it uses publicly available, freely available information, providing tremendous potential for safer non-business revenue.


BCOFGs loaded with nano-FexSy for the catalytic degradation of QNC: Contribution and mechanism of OFGs for reductive iron regeneration.
Biochar currently served as the support for dispersed metal nanoparticles and cooperated with pyrite to generate more reactive radicals in organic pollution degradation system. But the mechanism of interaction between biochar and pyrite has not been elucidated. In this paper, biochar with oxygen-containing functional groups (OFGs) served as a stable dispersant to prepare nano-FexSy loaded biochar materials (BCOFGs@nano-FexSy). BCOFGs coordinated with nano-FexSy to overcome its drawbacks, boosting QNC removal efficiency from 28.64% to 100%. The XPS and the linear sweep voltammetry (LSV) results revealed higher Fe(II) content and higher electron transfer rate on used BCOFGs@nano-FexSy, further validating that hydroxyl functional groups on biochar surface provided electrons to Fe(III) to achieve efficient Fe(II)/Fe(III) cycling. Based on comparative experiments and studies on the roles of iron, S(II) species and OFGs, we clearly revealed that OFGs on biochar materials surface coordinated with nano-FexSy to catalyze the degradation of QNC. The degradation efficiency of BCOFGs@nano-FexSy for QNC was still as high as 91.39% after five cycles, providing full demonstrations that OFGs and S(II) as the abundant electron donor coordinated with Fe species for QNC catalytic degradation and further enhanced the catalytic performance and stability of nano-FexSy.


Efficacy and Safety of LixiLan, a Titratable Fixed-Ratio Combination of Lixisenatide and Insulin Glargine, Versus Insulin Glargine in Type 2 Diabetes Inadequately Controlled on Metformin Monotherapy: The LixiLan Proof-of-Concept Randomized Trial.
This study assessed the efficacy and safety of LixiLan, a fixed-ratio, titratable, combination of 2 units insulin glargine (Gla-100) and 1 μg lixisenatide administered once daily via a single pen, versus Gla-100 in insulin-naïve type 2 diabetes on metformin. Participants were randomized to once-daily LixiLan (n = 161) or Gla-100 (n = 162) for 24 weeks, while continuing metformin. LixiLan and Gla-100 were started at 10 units/5 μg and 10 units, respectively, and titrated based on the Gla-100 requirement according to fasting plasma glucose levels. The primary objective was to test noninferiority (upper bound of the 95% CI ≤0.4%) of LixiLan in reducing HbA1c; if met, statistical superiority was tested. Secondary objectives included body weight changes, hypoglycemia, and safety. Baseline characteristics (mean age 57 years, diabetes duration 6-7 years, BMI 32 kg/m(2)) were similar between groups. At week 24, mean HbA1c was reduced from 8.0% (64 mmol/mol) at baseline to 6.3% (45 mmol/mol) and 6.5% (48 mmol/mol) with LixiLan and Gla-100, respectively, establishing statistical noninferiority and superiority of LixiLan (least-squared mean [95% CI] difference: -0.17% [-0.31, -0.04] {-1.9 mmol/mol [-3.4, -0.4]}; P = 0.01). HbA1c <7.0% (<53 mmol/mol) was achieved in 84% and 78% of participants (nonsignificant), respectively. LixiLan improved 2-h postmeal plasma glucose versus Gla-100 (least-squared mean difference: -3.17 mmol/L [-57 mg/dL]; P < 0.0001). Body weight was reduced with LixiLan (-1 kg) and increased with Gla-100 (+0.5 kg; P < 0.0001), with no increase in hypoglycemic events (∼25% in each group). The incidence of nausea (7.5%) and vomiting (2.5%) was low with LixiLan. LixiLan achieved statistically significant reductions to near-normal HbA1c levels with weight loss and no increased hypoglycemic risk, compared with insulin glargine alone, and a low incidence of gastrointestinal adverse events in type 2 diabetes inadequately controlled on metformin.


Urine kidney injury molecule-1: a potential non-invasive biomarker for patients with renal cell carcinoma.
KIM-1 staining is upregulated in proximal tubule-derived renal cell carcinoma (RCC) including clear renal cell carcinoma and papillary renal cell carcinoma, but not in chromophobe RCC (distal tubular tumor). This study was designed to prospectively examine urine KIM-1 level before and 1 month after removal of renal tumors. A total of 19 patients were eventually enrolled in the study based on pre-operative imaging studies. Pre-operative and follow-up (1 month) urine KIM-1 levels were measured. The urine KIM-1 levels (uKIM-1) were then normalized to urine creatinine levels (uCr). Renal tumors were also stained for KIM-1 using immunohistochemical techniques. The KIM-1-negative staining group included 7 cases, and the KIM-1-positive group consisted of 12 cases. The percentage of KIM-1-positive staining RCC cells ranged from 10 to 100 %, and the staining intensity ranged from 1+ to 3+. In both groups, serum creatinine levels were both significantly elevated after nephrectomy. In the KIM-1-negative group, uKIM-1/uCr remained at a similar level before (0.37 ± 0.1 ng/mg Cr) and after nephrectomy (0.32 ± 0.01 ng/mg Cr). However, in the KIM-1-positive group, elevated uKIM-1/uCr at 1.20 ± 0.31 ng/mg Cr was significantly reduced to 0.36 ± 0.1 ng/mg Cr, which was similar to the pre-operative uKIM-1/uCr (0.37 ± 0.1 ng/mg Cr) in the KIM-1-negative group. Our small but prospective study showed significant reduction in uKIM-1/uCr after nephrectomy in the KIM-1 positive group, suggesting that urine KIM-1 may serve as a surrogate biomarker for kidney cancer and a non-invasive pre-operative measure to evaluate the malignant potential of renal masses.


Protective Effects of Japanese Soybean Paste (Miso) on Stroke in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP).
Soybean isoflavones have been shown to reduce the risk of cerebral infarction in humans according to epidemiological studies. However, whether intake of miso can reduce the incidence of stroke in animal models remains unknown. In this study, we investigated the effects of soybean paste (miso) in an animal model of stroke. Stroke-prone spontaneously hypertensive rats (SHRSP) were fed a miso diet (normal diet 90%, miso 10%; final NaCl content 2.8%), a high salt diet (normal diet and NaCl 2.5%; final NaCl content 2.8%), or a low salt diet (normal diet; final NaCl content 0.3%). Kaplan-Meier survival curves revealed a significantly lower survival rate in the high salt group compared to the miso group (P = 0.002) and the low salt group (P ≤ 0.001). Large hemorrhagic macules were found in the cerebrum in the high salt group, whereas none were found in the other 2 groups. There were also fewer histological and immunohistochemical changes in the brain and kidneys in the miso group compared to the high salt group. Our results suggest that miso may have protective effects against stroke despite its high salt content.


Angiotensin: physiological role in water-deprivation-induced thirst of rats.
Cerebroventricular infusion of P-113, the blocking agent of angiotensin II, into rats for 75 minutes prior to their being allowed to drink, significantly attenuated their water intake when they had been deprived of water for 30 hours. However, a similar infusion had no effect on the food intake in rats fasted for 30 hours. The results indicate a physiological role for angiotensin II in the drinking response of rats deprived of water.


The individuals' discretionary behaviors at work. An overview and analysis of its growing interest.
Nearly forty years have passed since the term Organizational Citizenship Behavior appeared. Despite a current consensus among scholars about the citizenship gestures as prosocial acts of employees that benefit the organization, it does not apply commonly to the exponential growth of all OCB-related concepts. The concept's expansion has confused the researchers and practitioners, mainly when choosing the most appropriate instruments (constructs) and dimensions to use in their area of interest and context. A systematic literature review was conducted and 420 articles were analyzed. Results point that the trends on OCB-like behaviors goes higher, with an average annual growth rate of new studies of 3.13%. United States (39%) and China (25%) lead but some "under-studied" contexts like Africa, Latin America, the Caribbean, and Oceania start being studied towards OCB. New trends appear in the spectrum of the many different domains and disciplines related to OCB, while leadership and task performance remain the most studied domains and disciplines. In future studies, researchers must freely choose the OCB dimensions and constructs they want to use or adapt to meet their needs and research needs since there is no written rule about their use, only the care to be taken with the context and discipline studying.


Energetic cost of feeding territories in an Hawaiian honeycreeper.
By analysis of time budgets the daily energy expenditure in territorial individuals of a Hawaiian honeycreeper (Vestiaria coccinea, Fam. Drepanididae) were estimated during the nonbreeding season and compared to that of nonterritorial individuals. The mean rise in living costs was 2.3 kcal/24 h or 17% of the nonterritorial energy budget. The most costly territorial behavior was advertisement rather than chasing, and total territorial cost was seen to be little affected by the number of intruders or the size of the territory. These results are compared with data on feeding (nonbreeding) territories of other nectar-feeding birds. The suggestion is made that hummingbirds may be more likely to develop nonbreeding territorial behavior in any set of environmental circumstances than are honeycreepers because of relatively lower total cost of advertisement plus chasing.


Effects of microvibration stimulation on developmental potential of discarded germinal vesicle oocytes of human.
This research aims to study the effects of continuous microvibration stimulation on the parthenogenetic development of human germinal vesicle oocytes. Ninety-five discarded germinal vesicle oocytes from intracytoplasmic sperm injection treatment (ICSI) cycles performed at Amcare Women's & Children's Hospital between January and December 2021 were used for conventional static culture as well as 10 Hz microvibration culture. We investigated the differences between the two groups in terms of oocyte maturation rate, parthenogenetic activation rate, and parthenogenetic blastocyst formation rate. The static culture and 10 Hz microvibration culture of 95 oocytes showed that the parthenogenetic blastocyst formation rate in the microvibration culture group was significantly higher than those in the traditional static culture group. A continuous microvibration stimulation can significantly improve the parthenogenetic developmental potential of human immature oocytes.


'Stranger' child-murder: issues relating to causes and controls.
Most industrialised countries are concerned with a perceived increase in the killing of children and adolescents by strangers. Though reliable statistics are lacking, the growth of serial murder suggests that more young persons may be at risk than ever before. Explanations, either of a psychological or sociological kind, of child murder by strangers are inadequately developed. Despite the tendency to see such killers as psychiatrically ill a number of studies suggest that the majority of offenders do not differ significantly, at least in psychological traits, from non-offenders. Subcultural and other sociological perspectives stressing "social disadvantage" have low levels of exploratory power and do not assist greatly in understanding child killings. Despite sketchy and contradictory evidence on the effects of the media on sexual and violent crime case study material supports the view that pornography, including popular music, may increase the propensity of individuals to commit atrocities. Counter-measures to control stranger child killing lie in more sophisticated law enforcement (profiling and computer links between police forces) long periods of incarceration of the offender and more sophisticated analyses of the crimes.


Serum antitrypsin synthesis by the isolated perfused rat liver.
The isolated perfused rat liver synthesizes antitrypsin activity in a linear fashion as long as 24 hr. The rate of synthesis may be ten times the rate necessary for physiologic levels in vivo. These data are compatible with the liver as the principal site of synthesis of serum antitryptic activity in the rat. The antitrypsin activity of the rat perfusate resembles that of normal human plasma in liability to heat (56 degrees) and to acid (below pH 6) and in apparent molecular size (elution from Sephadex G-200).


The immunomodulatory action of inosiplex in relation to its effects in experimental viral infections.
The effect of inosiplex (Isoprinosine) on viral replication, experimental viral infections and host immune functions has been examined. Inosiplex was found to have a broad spectrum of antiviral activity, inhibiting the RNA viruses, influenza (INFV) and parainfluenza (PIV), as well as the DNA viruses, herpes simplex (HSV) and vaccinia (VACV). However, the antiviral effects were modest when compared to amantadine and adenine arabinoside (ARA-A). Inosiplex in vivo caused a statistically significant increase in survival of treated animals (hamster, mice) infected with RNA or DNA viruses. This effect of inosiplex was apparent in animals which were previously immunosuppressed. Inosiplex, at optimal dose, conferred total protection in treated mice against secondary influenza infection. Since this was accompanied by statistically significant increases in serum anti-hemagglutinin and anti-neuraminidase titers, an effect of inosiplex on host defenses against secondary viral infection was implicated. This effect was further demonstrated by passive transfer of protection by splenocytes from inosiplex-treated donors to untreated recipients. Inosiplex was found to enhance the mitogen- (PHA-, ConA and MLC-) induced blastogenesis of lymphocytes from untreated mice. The LPS response was not affected. Inosiplex added in vitro caused a dose-dependent increase in the primary immune anti-SRBC response in vitro, as determined by direct and indirect PFC; there was also a dose-dependent effect on the secondary in vitro direct and indirect PFC responses. Inosiplex in vivo enhanced the primary immune response to SRBC, as determined by direct PFC assay; this was also the case for immunosuppressed mice. The drug enhanced delayed type hypersensitivity to picryl chloride in the mouse. Macrophage function was also enhanced by inosiplex, as was apparent from phagocytosis of SRBC. Gamma interferon production from murine lymphocytes was augmented by inosiplex in vitro. Treatment with inosiplex had no effect on natural killer cells or on antibody dependent cellular cytotoxicity. Thus, the pronounced effect of inosiplex on secondary viral infections may result through two different mechanisms: a direct antiviral effect and an elevation of multiple parameters of host immunity, which are usually compromised during viral infection. The latter mechanism may be the more important.


Lipid-bound sugars in malignant human breast tumors. Partial characterization of mannosyl and glucosyl transferase activities.
Microsomal preparations from malignant human breast tumors catalyzed the transfer of mannose and glucose from GDP-[14C]-Man and UDP-[14C]-Glc into lipid-linked sugars and glycoprotein-like substances. As judged by several criteria the obtained lipid-linked monosaccharides behaved as dolichyl phosphate mannose and dolichyl phosphate glucose whereas lipid-linked oligosaccharides behaved as polyprenyl diphosphate derivatives. The optimum conditions for mannosyl- and glucosyl-transfer reactions and the effect of dolichyl phosphate, detergent and EDTA on incubation mixture were described.


Circulating acylated and total ghrelin and galanin in children with insulin-treated type 1 diabetes: relationship to insulin therapy, metabolic control and pubertal development.
To study the circulating levels of two gut-derived peptides in children with type 1 (insulin-dependent) diabetes mellitus (IDDM). Plasma levels of ghrelin, both total ghrelin (TG) and the acylated form (AG), and galanin and their relationships with insulin dosage, metabolic control, IGFBP-1, body mass and pubertal development were evaluated in 91 children, aged 11.1 +/- 2.7 years, affected by IDDM and treated with insulin. Ninety-one healthy children were selected as controls. Body mass index (BMI)-adjusted levels of both forms of ghrelin were reduced in IDDM compared with healthy subjects, with greater values in prepubertal than pubertal IDDM subjects. A negative association was found between AG and fasting insulin serum levels and insulin resistance [measured by using the homeostasis model assessment of insulin resistance (HOMA IR)] among the healthy children. IDDM children showed a negative association of their plasma ghrelin (both acylated and total) with daily insulin dosage, and the three adiposity indices (BMI, skinfold thickness and percentage fat mass). IGFBP-1 levels were higher among the IDDM children without any association with ghrelin serum values. BMI-adjusted plasma levels of galanin were higher among IDDM compared to healthy subjects, irrespective of sex or pubertal development. Greater values for galanin were found among pubertal than prepubertal subjects in both groups without any significant differences between the genders. A positive association was found between galanin and BMI in both groups and between galanin and haemoglobin A1c (HbA1c) among the IDDM children. No relationship existed between either galanin and fasting serum insulin among the healthy subjects or galanin and both insulin dosage or duration of treatment among the IDDM subjects. The associations found between both ghrelin and galanin with adiposity indices could be considered as an indirect signal of involvement of the two peptides in the development of the nutritional status of the IDDM adolescents. The reduction in both forms of ghrelin could be involved in the development of the body mass increase of IDDM subjects with opposite effects, either influencing insulin sensitivity or exerting a compensatory restraint of feeding.


Differential functions of RhoGDIβ in malignant transformation and progression of urothelial cell following N-butyl-N-(4-hydmoxybutyl) nitrosamine exposure.
Functional role of Rho GDP-dissociation inhibitor beta (RhoGDIβ) in tumor biology appears to be contradictory across various studies. Thus, the exploration of the molecular mechanisms underlying the differential functions of this protein in urinary bladder carcinogenesis is highly significant in the field. Here, RhoGDIβ expression patterns, biological functions, and mechanisms leading to transformation and progression of human urothelial cells (UROtsa cells) were evaluated following varying lengths of exposure to the bladder carcinogen N-butyl-N-(4-hydmoxybutyl) nitrosamine (BBN). It was seen that compared to expression in vehicle-treated control cells, RhoGDIβ protein expression was downregulated after 2-month of BBN exposure, but upregulated after 6-month of exposure. Assessments of cell function showed that RhoGDIβ inhibited UROtsa cell growth in cells with BBN for 2-month exposure, whereas it promoted the invasion of cells treated with BBN for 6 months. Mechanistic studies revealed that 2-month of BBN exposure markedly attenuated DNMT3a abundance, and this led to reduced miR-219a promoter methylation, increased miR-219a binding to the RhoGDIβ mRNA 3'UTR, and reduced RhoGDIβ protein translation. While after 6-mo of BBN treatment, the cells showed increased PP2A/JNK/C-Jun axis phosphorylation and this in turn mediated overall RhoGDIβ mRNA transcription and protein expression as well as invasion. These findings indicate that RhoGDIβ is likely to inhibit the transformation of human urothelial cells during the early phase of BBN exposure, whereas it promotes invasion of the transformed/progressed urothelial cells in the late stage of BBN exposure. The studies also suggest that RhoGDIβ may be a useful biomarker for evaluating the progression of human bladder cancers.


Depolarizing effect of noradrenaline on neurons of the rat supraoptic nucleus in vitro.
Noradrenaline (NA) (1-100 microM) was applied to 41 neurons recorded intracellularly from the supraoptic nucleus (SON) of the rat hypothalamic slice preparation; 34 (83%) neurons showed membrane depolarization which was dose-dependent. The depolarization was frequently accompanied by decreased membrane resistance, increased firing rate and increased fluctuations in membrane potential. Following the application of the alpha-agonist, phenylephrine, 10 out of 11 neurons tested showed similar responses, while the beta-agonist, isoproterenol, caused no changes in 6 out of 7 SON cells. We found no difference in responsiveness between neurons having a 'phasic' or a 'non-phasic' pattern of firing. We conclude that NA depolarized and increased the firing rate of both vasopressin- and oxytocin-containing neurons through an action on alpha-adrenergic receptors.


Outcome Analysis of Microlaryngeal Surgery for Benign Lesions of Vocal Cord Using Videostroboscopy and Voice Handicap Index.
Benign vocal cord mass lesions are common causes of dysphonia which are often surgically correctable. They include lesions like vocal polyps, vocal cysts, vocal nodules and Reinke's edema. A prospective study of 30 patients was carried out at SMS medical college and hospital between April 2014 to November 2015 after institutional ethical committee clearance. The purpose of our study was to evaluate outcome of microlaryngeal surgery for benign lesions of vocal cord using videostroboscopy and voice handicap index. All cases between the age group 15-60 years with clinical evidence of benign lesions of vocal cord were included in study. Preoperative amplitude, mucosal wave, glottic closure was seen by videostroboscopy and subjective assessment of severity of handicap in voice was assessed by set of questionnaire using voice handicap index (Jacobson et al. in Am J Speech Lang Pathol 6: 66-70, 1997). Postoperative follow up was done at 3rd week and 10th week, and outcome of microlaryngeal surgery was assessed using videostroboscope and voice handicap index. At the end of study data was compiled systemically and analysed using paired 't' test and Chi square test. Our study observed statistically significant improvement in amplitude and mucosal wave and glottic closure. Subjective improvement in perception of severity of handicap in voice was analysed by voice handicap index which shows statistically significant data. Overall our study conclude microlaryngeal surgery as an effective way for improvement in speech parameters, that can be assessed by use of videostroboscopy and voice handicap index.


The crystal structure of troponin C in complex with N-terminal fragment of troponin I. The mechanism of how the inhibitory action of troponin I is released by Ca(2+)-binding to troponin C.
Troponin (Tn), the complex of three subunits (TnC, TnI, and TnT), plays a key role in Ca2+ dependent regulation of muscle contraction. To elucidate the interactions between the Tn subunits and the conformation of TnC in the Tn complex, we have determined the crystal structure of TnC in complex with the N-terminal fragment of TnI (TnI1-47). The structure was solved by single isomorphous replacement method in combination with multiple wavelength anomalous dispersion data. The refinement converged to a crystallographic R-factor of 22.2% (R-free = 32.6%). The central, connecting alpha-helix observed in the structure of uncomplexed TnC (TnCfree) is unwound at the center and bent by 90 degrees. As a result, the TnC in the complex has a compact globular shape with direct interactions between the N- and C-lobes, in contrast to the elongated dumb-bell shaped molecule of uncomplexed TnC. The 31-residue long TnI1-47 alpha-helix stretches on the surface of TnC and stabilizes its compact conformation by multiple contacts with both TnC lobes. The amphiphilic C-terminal end of the TnI1-47 alpha-helix is tightly bound in the hydrophobic pocket of the TnC C-lobe through 38 van der Waals interactions. The results indicate the major difference between integrated (TnC) and isolated (calmodulin) Ca2+ receptors. The TnC/TnI1-47 structure suggests the model for a novel regulatory TnI segment bound to TnC and implies the mechanism of how Tn regulates the muscle contraction.


Acute respiratory failure revealing Guillain-Barre syndrome.
This article reports the occurrence of Guillain-Barre syndrome in a critically ill patient manifesting as a "difficult-to-wean" patient. This uncommon but possible etiology is worth noting by physicians in the intensive care unit.


Coupling of folding and binding for unstructured proteins.
There are now numerous examples of proteins that are unstructured or only partially structured under physiological conditions and yet are nevertheless functional. Such proteins are especially prevalent in eukaryotes. In many cases, intrinsically disordered proteins adopt folded structures upon binding to their biological targets. Many new examples of coupled folding and binding events have been reported recently, providing new insights into mechanisms of molecular recognition.


CATP is a critical component of the Neurospora circadian clock by regulating the nucleosome occupancy rhythm at the frequency locus.
Rhythmic frq transcription is essential for the function of the Neurospora circadian clock. Here we show that there is a circadian histone occupancy rhythm at the frq promoter that is regulated by FREQUENCY (FRQ). Using a combination of forward genetics and genome sequencing, we identify Clock ATPase (CATP) as an essential clock component. Our results demonstrate that CATP associates with the frq locus and other WCC target genes and promotes histone removal at these loci to allow circadian gene transcription. These results indicate that the rhythmic control of histone occupancy at clock genes is critical for circadian clock function.


Study of the antitumour effects and the modulation of immune response by histamine in breast cancer.
The aim of this work was to improve the knowledge of the role of histamine in breast cancer by assessing the therapeutic efficacy of histamine and histamine H4 receptor (H4R) ligands in a triple-negative breast cancer (TNBC) model developed in immunocompetent hosts. By using publicly available genomic data, we further investigated whether histidine decarboxylase (HDC) could be a potential biomarker. Tumours of 4T1 TNBC cells were orthotopically established in BALB/c mice. Treatments employed (mg kg-1): histamine (1 and 5), JNJ28610244 (H4R agonist, 1 and 5) and JNJ7777120 (H4R antagonist, 10). Increased HDC gene expression is associated with better relapse-free and overall survival in breast cancer patients. Histamine treatment (5 mg kg-1) of 4T1 tumour-bearing mice reduced tumour growth and increased apoptosis. Although no immunomodulatory effects were observed in wild-type mice, significant correlations between tumour weight and cytotoxic lymphocyte infiltration were detected in H4R knockout mice. H4R agonist or antagonist differentially modulated tumour growth and immunity in 4T1 tumour-bearing mice. Histamine plays a complex role and stands out as a promising drug for TNBC treatment, which deserves to be tested in clinical settings. HDC expression level is associated with clinicopathological characteristics, suggesting a prognostic value in breast cancer.


Cystic fibrosis in adults: a changing scene.
Cystic fibrosis is no longer a terminal illness of childhood and mean survival is now over 30 years. Adult patients with atypical CF are increasingly being diagnosed. In Israel, all patients are still followed in pediatric centers. To describe our experience with adult CF, stressing the importance of adult-related health and psychosocial issues. Twenty-five CF patients aged 20-50 years, constituting 44% of the 57 patients followed at our center, were analyzed for pulmonary and extrapulmonary features and management. Nineteen were diagnosed as children and 6 as adults. Nineteen were pancreatic-insufficient and 6 were pancreatic-sufficient, including 5 diagnosed as adults. Pulmonary status was usually stable, with forced expiratory volume in 1 second 66.3 +/- 21% (mean +/- SD) and no difference between pancreatic-sufficient and insufficient patients. The latter had more hemoptysis, Pseudomonas infection, intestinal obstruction, liver disease and diabetes. Two patients died of malignancy and two of advanced lung disease. A majority received continuous inhaled and oral antibiotics, bronchodilators, Dnase, physiotherapy and periodic home intravenous antibiotics. Psychosocial functioning was excellent: 60% were employed, 36% were married and 40% had children (none with CF). Patients diagnosed as adults had mild multisystem disease or isolated severe lung disease. CF adults generally have a good quality of life. Advances in understanding the CF defect and a plethora of new treatment modalities bode well for the future. Patients must be maintained in optimal condition to reap the benefits, and there is an urgent necessity for adult physicians to develop expertise in CF.


Copper-induced heart malformations in hamsters.
The injection of copper citrate into pregnant golden hamsters induces a specific pattern of cardiovascular malformations in their embroys. The syndrome consists of double-outlet right ventricle, pulmonary hypoplasia and a ventricular spetal defect.


Incidence and prevalence of generalized pustular psoriasis in multiethnic Johor Bahru, Malaysia: a population-based cohort study using routinely captured electronic health records in the Teleprimary Care (TPC®) clinical information system from 2010 to 2020.
There is limited understanding of the epidemiology of generalized pustular psoriasis (GPP) internationally, with no population-based estimates of GPP in South East Asia. To determine the incidence and prevalence of GPP in the Malaysian population and characterize its flares and trigger factors. We conducted a population-based cohort study using the Teleprimary Care database between January 2010 and December 2020. We identified 230 dermatologist-confirmed GPP cases using International Classification of Diseases, 10th revision, diagnostic codes. Annual prevalence and incidence rates were stratified by age, sex and ethnicity. We compared data regarding flares and trigger factors for patients with GPP who had associated psoriasis vulgaris (PV) with those who did not have associated PV. The prevalence of GPP was 198 per million (267 women, 127 men) and incidence was 27.2 per million person-years [95% confidence interval (CI) 22.8-31.6]; 35.3 (28.4-42.2) per million person-years for women and 18.3 (13.1-23.5) per million person-years for men. Rates were higher in Chinese individuals [prevalence 271 per million; incidence 41.6 per million person-years (28.9-54.3)] than in the Malay population [prevalence 186; incidence 24.6 (19.4-29.7)] or the Indian ethnic group [prevalence 179; incidence 25.0 (13.8-36.3)]. Annual prevalence was consistently higher in women than in men and highest among the Chinese population, followed by the Indian and Malay populations. Overall, 67% of patients with GPP had associated PV. The prevalence and incidence of GPP without PV were lower than GPP with PV at 66 vs. 132 per million and 19.3 (95% CI 15.6-23.0) vs. 8.0 (95% CI 5.6-10.3) per million person-years, respectively. The mean age at GPP onset was 42.7 years (SD 18.4). A bimodal trend in the age of GPP onset was observed, with first and second peaks at age 20-29 years and age 50-59 years, respectively. Disease onset was significantly earlier in patients with GPP without PV than in those with PV [mean age 37.5 years (SD 20.7) vs. 44.9 years (SD 17.0), P = 0.026]. Flares occurred more frequently in patients without PV than in those with PV [mean number of flares per patient per year was 1.35 (SD 0.77) vs. 1.25 (SD 0.58), P = 0.039]. Common triggers of flares in patients with GPP who did not have PV were infections, pregnancy, menstruation and stress, whereas withdrawal of therapy, particularly systemic corticosteroids, was a more frequent trigger in patients with GPP who also had PV. Our findings contribute to the global mapping of GPP, which will help inform the management of this rare condition.


[A case of rapid palatal expansion treated with a double telescopic screw appliance].
A case of maxillary hypoplasia with serious crowding in the upper arch, treated by the utilization of a special telescopic double screw permitting rapid expansion of the palate is described.


Protective efficacy of commercial Newcastle disease vaccines against challenge of goose origin virulent Newcastle disease virus in geese.
Since 1997, severe outbreaks of Newcastle disease (ND) in geese in many regions throughout China have resulted in high morbidity and mortality, and great economic loss to farmers; however, no licensed, specific vaccine is yet available for this disease in China. In this study, goslings were immunized with different combinations and dosages of several commercial ND vaccines including La Sota vaccine, Mukteswar vaccine, recombinant live vaccine against avian influenza (AI) and ND (rL-H5 strain), and inactivated ND oil-emulsion vaccine (La Sota strain). The protective effects were evaluated based upon the level of antibody response and the degree of protection against the goose-origin virulent NDV strain. The result showed that two doses (i.e., one more than that for chicken) of La Sota vaccine priming, followed by 2-5 doses of Mukteswar vaccine boosting 2-3 weeks later, not only induced higher HI antibody levels, but also conferred longer-lasting protection. This immunization procedure can be recommended for prevention of ND in geese.


Comparison of various chemometric approaches for large near infrared spectroscopic data of feed and feed products.
In the present study, different multivariate regression techniques have been applied to two large near-infrared data sets of feed and feed ingredients in order to fulfil the regulations and laws that exist about the chemical composition of these products. The aim of this paper was to compare the performances of different linear and nonlinear multivariate calibration techniques: PLS, ANN and LS-SVM. The results obtained show that ANN and LS-SVM are very powerful methods for non-linearity but LS-SVM can also perform quite well in the case of linear models. Using LS-SVM an improvement of the RMS for independent test sets of 10% is obtained in average compared to ANN and of 24% compared to PLS.


Ordering genetic testing by neurologists: points to consider.
A significant challenge limiting the comprehensive utilization of genomic medicine is the lack of timely access to genetics specialists. Although neurologists see patients for whom genetic testing should be considered, the knowledge regarding the choice of the optimal genetic test for each case and the management of the test results are out of the scope of their everyday practice. In this review, we provide a step-by-step guide for non-geneticist physicians through the decision-making process when ordering diagnostic genetic testing for monogenic neurological diseases and when dealing with their results.


Differentiating motives for nonmedical prescription stimulant use by personality characteristics.
Nonmedical prescription stimulant use (NPS) is increasing, particularly among college students. College students typically engage in NPS for cognitive enhancement, recreational, and appetite/weight-related purposes; however, little research has used these motives to identify specific risk for, or consequences of, NPS. Moreover, there may be unique risk factors for motive-specific NPS that have yet to be explored, such as relevant personality traits (i.e., distress tolerance, impulsivity, and perfectionism) that are associated with NPS in general. Therefore, this study aimed to examine whether NPS users and nonusers could be differentiated via facets of impulsivity, perfectionism, and distress tolerance, and whether users could be further differentiated by reported motive for use based on these traits. Midwestern university undergraduate students (N = 668) who were enrolled in a psychology research pool completed an online survey assessing demographics, NPS and motives, and measures of distress tolerance, impulsivity, and perfectionism. Participants were primarily female (78%) and aged 18-54 (M = 20.10, SD = 3.19) years. Univariate and multivariate analysis of variance tests revealed associations between lifetime NPS and higher impulsivity, higher perfectionism, and lower distress tolerance. Further tests revealed NPS for appetite/weight-related purposes was associated with lower distress tolerance, while NPS for recreational purposes was associated with higher impulsivity. These findings contribute novel information regarding NPS motives and personality constructs. This information may aid in comprehensive identification of high-risk individuals for NPS and inform the development of specialized prevention and intervention efforts.


Clinical and radiological results of lumbar microdiskectomy technique with preserving of ligamentum flavum comparing to the standard microdiskectomy technique.
The ligamentum flavum is the anatomic plane between the epidural and laminar-extralaminar spaces, which should be meticulously preserved for a possible reoperation. Preservation of the ligamentum flavum together with other epidural anatomic structures, such as epidural fat tissue and venous plexuses, and limited removal of the lamina are important components in preventing epidural fibrosis that may be the cause of failed back surgery syndrome. One thousand five hundred patients underwent microdiskectomy with preservation of the ligamentum flavum over an 8-year period. This technique was performed with a small incision using an 18 mm-width mini Taylor retractor. The ligamentum flavum was released and preserved as a 3-sided flap. The disk content was totally removed and a pediculated fat graft was used to cover the root at the end. Four hundred patients operated on with the ligamentum flavum preserving technique were randomly selected for this study (Group 1). Their results were compared with those of 200 patients who were operated on with the standard microdiskectomy (Group 2). Standard microdiskectomy technique was performed with fenestration and foraminotomy and the ligamentum flavum was partially or totally excised. Early clinical outcome was classified as excellent, good, fair, poor, or failure. The clinical mean follow-up period in Group 1 was 36.8 months and in Group 2 it was 32.4 months. One hundred patients from each group had computed tomographic scans with contrast administration performed at least one year after the operation to examine late epidural fibrosis. A questionnaire was given to all patients at least 3 times during the late follow-up period. The questionnaire required patients to describe their relief of pain, job performance, and abstinence from narcotic analgesic use. Early clinical outcome (fourth postoperative week) in Group 1 was satisfactory in 96.75% of the patients, whereas it was satisfactory in only 81.5% in Group 2 (p < 0.001). The radiological examinations revealed fibrosis in 18% of the patients in Group 1 and 37% in Group 2 (p < 0.001). None of the patients in Group 1 were readmitted because of fibrosis-related symptoms. The reoperation rate in Group 1 was 4.5%. The recurrence rate was 1.75% and disc at another level was 2.5%. One patient was reoperated because of a suture granuloma. In Group 2, the reoperation rate was 9% (p < 0.05). The recurrence rate was 4.5%, disc at another level was 3.5% and extensive epidural fibrosis was 1%. Two patients who underwent surgery for epidural fibrosis in this group had disappointing outcomes. Overall success rate based on the questionnaire was 91% in Group 1 and 76% in Group 2 (p < 0.001). The ligamentum flavum preserving technique is useful in achieving a favorable long-term outcome, and reoperation, if necessary, is easier and safer.


[Effect of selection techniques on chromosome and ultrastructure of human spermatozoa].
To know the effect of different selection techniques on chromosome abnormality rate and the percentage of spermatozoa with relatively intact head ultrastructure in human sperm. The selection techniques of swim-up, Percoll density gradient centrifugation and doule-flection tube were used to observe sperm chromosome abnormality rate, sex chromosomal ratio and the percentage of spermatozoa with relatively intact head ultrastructure. The sperm chromosome abnormality rate, sex chromosomal ratio and the percentage of spermatozoa with relatively intact head ultrastructure remained unchanged after the application of the three selection techniques(P > 0.05). The three selection techniques used in this study neither increase the damage to sperm ultrastructure nor exert effects on human chromosome.


Incomplete prenatal diagnosis of G-trisomy mosaicism.
Chromosomal mosaicism is difficult to detect in prenatal diagnosis, and it seems even more difficult to predict its significance correctly. We present a case, in which G-trisomy mosaicism was diagnosed prenatally but was not verified in the aborted fetus. A practical approach to suspected fetal mosaicism in prenatal diagnosis is proposed.


[Hypofractionation and radiotherapy: "the eternal return"].
Hypofractionation is not a new idea in radiotherapy. The use of a few high-dose fractions has been proposed by some pioneers of our specialty in the early years of the 20th century. Hypofractionation then reappeared several times in the next decades, based on successive radiobiological concepts, a number of them having been shown to be wrong. The nominal single dose (NSD), for example, so fashionable in the 1970's, dramatically underestimated the late toxicity of the high-dose fractions. Consequently, the NSD was directly responsible for a significant increase of the incidence and of the severity of late complications in large cohorts of patients. The linear-quadratic model (LQ) unequivocally improved our understanding of fractionation sensitivity, but one has to keep in mind its limitations, both in the areas of low and high doses per fraction. For more than a decade, prostate cancer has been the subject of fierce discussions about its sensitivity to fractionation. A number of studies have suggested an unusually low (for a malignant tumor) alpha/beta ratio. However, the available data do not allow a precise evaluation of this ratio; "very low" (1.5 Gy), with an advantage of hypofractionation in terms of local control? Or simply "low" (3-4 Gy), only allowing a reduction of the total number of fractions (with a dose adequately reduced)? While waiting for complementary data, it is advised to remain very careful when modifying the classical schemes towards hypofractionation.


Shengmai Yin formula exerts cardioprotective effects on rats with chronic heart failure via regulating Linoleic Acid metabolism.
The objective of this study was to investigate the protective effects of Shengmai Yin(SMY) on rats with chronic heart failure(CHF).Sprague-Dawley rats were used to establish a CHF animal model via ligation of the left anterior descending branch of the coronary artery and exhaustive swimming.Echocardiography, serum biochemical indicators and histopathology were used to evaluate the pharmacodynamics of SMY in CHF rats.UPLC-Q-TOF/MS analysis based on serum was performed to identify the potential metabolites in the pathological process of CHF. Metabolic pathway analysis was carried out to elucidate the metabolic network associated with SMY treatment of CHF.Moreover,quantitative real-time PCR (qRT-PCR), Western blotting (WB), and Enzyme-linked immunosorbent assay (ELISA) were used to measure the RNA and protein expression levels in related pathways. Results revealed that SMY significantly restored the cardiac function of CHF rats, reduced the serum biochemical indicators, and alleviated cardiac histological damage. Metabolomics analysis shows that the therapeutic effect of SMY for CHF involves 14 biomarkers and 8 metabolic pathways, especially linoleic acid pathway, to be influenced, which implied the potential mechanism of SMY in treating CHF. Two key indicators Lipoxygenase arachidonic acid 15 lipoxygenase (ALOX15) and Cytochrome P450 1A2(CYP1A2) of linoleic acid metabolism pathway were verified by RT-PCR, WB and ELISA. Verification result showed that compared with the model group, expression levels of ALOX15 and CYP1A2 in SMY group were lower. In conclusion, SMY has cardioprotective effect on chronic heart failure rats, and its mechanism may be related to linoleic acid metabolism pathway.


Retrospective analysis of clinical and virological parameters of influenza cases at four university hospitals in Germany, 2015.
We conducted a retrospective observational study at four German university hospitals of patients with laboratory-confirmed influenza in 2014/2015. Overall, a fatality rate of 8% was observed. Significantly more A(H1N1)pdm09 patients were admitted to ICU compared to those with A(H3N2). However, fatal outcome was not significantly increased among A(H1N1)pdm09 cases. Nosocomial infections were seen in 17% of cases. Systematic collection of data from hospitals will complement national influenza surveillance.


Evaluation of an infrared thermography camera for measuring body temperature in dairy calves.
The objective of this diagnostic accuracy study was to validate an infrared thermography (IRT) camera and its software (FLIR One, FLIR, Global) for accuracy and precision for ocular temperature readings to serve as a proxy for rectal temperature in commercially housed calves. A total of 318 male Holstein calves were enrolled into this study from the day of arrival to a calf rearing facility until 14 d later. Researchers took an ocular temperature reading using an IRT camera, and a rectal temperature on each calf each day in the morning. The reference standard method for body temperature in the calves was rectal temperature. We assessed the data for agreement between the IRT and the reference standard using Pearson correlations by calf (accuracy), coefficients of determination (precision), and Bland-Altman plots for bias. In addition, a logistic regression model was built using the reference method as the outcome, with IRT as an explanatory variable to assess the diagnostic accuracy of IRT as an indicator of fever (rectal temperature ≥39.5°C). There was a negligible correlation between the IRT readings and rectal temperature (r = 0.22) and the coefficient of determination for IRT to predict rectal temperature was negligible (R2 = 0.05), suggesting poor precision. The average mean difference between the IRT data and rectal temperature was 0.55°C, and the differences between IRT and rectal formed a linear line around the mean difference, suggesting the Bland-Altman analyses showed proportional error and bias. The optimal probability cut-off for IRT readings for fever was at 39.5°C, and had a receiver operating characteristic area under the curve of 0.67, a sensitivity of 61%, a specificity of 71%, and 78% (3,134/4,427) of the samples were correctly labeled as either having a fever or not using IRT readings. In summary, the IRT camera and software were not validated for serving as a proxy for rectal temperature in commercially housed calves due to poor precision, and proportional error partially explained by ambient environmental conditions. We suggest that this infrared thermography system should not replace rectal temperature readings for use in commercially housed calves.


The relationship of mammary temperature to parturition in human subjects.
Four hundred and seventy thermography studies were performed on 210 women to measure mammary temperature prior to, during, and immediately following pregnancy. Mean mammary temperature of 33.3 +/- 0.1 degrees C. (S.E.M.) obtained in 14 nonpregnant patients increased to 34.2 +/- 0.1 C. (S.E.M.) by nine weeks of gestation (p less than 0.01). The difference between mammary and sternal temperature was negative in the nonpregnant state and became positive after 18 weeks of pregnancy. Mammary temperature remained significantly higher in the pregnant group than in the nonpregnant group (p less than 0.001) up to term. In six postpartum patients, a further increase from prepartum values to 35.4 +/- 0.6 degrees C. (S.E.M.) occurred. The results suggest that relatively large changes in mammary blood flow and/or metabolic rate take place in human subjects in early pregnancy and on the day following parturition.


Are females selected against in ephemeral habitats? The case of a holometabolous insect (Chironomus pulcher).
Adults of the rain-pool dwelling midge Chironomus pulcher are sexually dimorphic with females larger than males. This difference is achieved by females remaining in the growing larval stage for longer. When food is scarce, as under crowded conditions, the average size of both sexes is reduced, but the difference between them is maintained. However, more females perish, presumably because they are unable to achieve a minimum female size. Under conditions of crowding, there is thus a switch in favour of males. Since crowding due to a diminishing habitat is a frequent event in rain-pools, males seem fitter than females in C. pulcher. This paradox is discussed.


Two-dimensional gel electrophoresis analysis in simultaneous influenza pneumonia and bacterial infection in mice.
Severe pneumonia is found in simultaneous influenza pneumonia and bacterial infection, and suggests a relationship with immunological mechanisms. Here, we performed two-dimensional gel electrophoresis to detect immunological molecules related to the fulminant pneumonia caused by influenza virus and Streptococcus pneumoniae co-infection in mice. We found two spots that were expressed strongly in co-infected mouse lungs, compared with S. pneumoniae or influenza virus singly infected mouse lungs. The spots were analysed by mass spectrometry, and identified as alpha-1 anti-trypsin (A1AT), known as an anti-protease for neutrophil-derived proteolytic enzymes, and creatine kinase, which reflects a greater degree of lung damage and cell death. A1AT expression was increased significantly, and proteolytic enzymes from neutrophils, such as neutrophil elastase, myeloperoxidase and lysozyme, were also secreted abundantly in influenza virus and S. pneumoniae co-infected lungs compared with S. pneumoniae or influenza virus singly infected lungs. These data suggest that A1AT may play a central role as a molecule with broad anti-inflammatory properties, and regulation of the neutrophil-mediated severe lung inflammation is important in the pathogenesis of co-infection with influenza virus and bacteria.


Transforming growth factor-alpha and nonsyndromic cleft lip with or without palate or cleft palate only in Kelantan, Malaysia.
To determine the frequency of the transforming growth factor-alpha (TGFalpha) Taq1 polymorphism in nonsyndromic cleft lip with or without cleft palate (CL+/-P) and cleft palate only (CP) in Kelantan, Malaysia. The study was conducted at the Combined Cleft Clinic and at the Human Genome Centre in Hospital Universiti Sains Malaysia in Kelantan, Malaysia. We examined the C2/Taq1 variant of the TGFalpha gene in 46 patients with nonsyndromic CL+/-P or CP only and in 33 controls. The TGFalpha genotype frequencies in patients were compared with those in controls using the chi-square or Fisher exact test. DNA samples were obtained from peripheral blood. No association was found between TGFalphaTaq1 polymorphism and CL+/-P or CP in this case-control study. In addition, no homozygosity for the rare allele C2 was noted in CL+/-P, CP, or the controls. No evidence of TGFalphaTaq1 polymorphism was observed in association with CL+/-P and CP in this study.


Data-driven cascade control system: Response estimation and controller design.
In this study, we propose a data-driven design method for a cascade control system with inner and outer control loops. First, the input-output response of a controlled plant, which varies with the controller parameters of a fixed-structure inner-outer control law, is estimated directly from open-loop input-output data. Next, based on the estimated response, the controller parameters are optimized to minimize the difference between a reference model with a controlled closed-loop system. In the proposed method, the response of a fictitious reference input, which varies with the controller parameters, is estimated, and then the closed-loop response is estimated. Therefore, a closed-loop input-output data is not required, and the controller parameters are determined directly from an open-loop input-output data. Furthermore, the time constant of a reference model is also optimized so as to reduce the control error. The proposed method is compared with both conventional single-loop and cascade data-driven methods by means of numerical examples.


Leptin and its receptors: regulators of whole-body energy homeostasis.
Leptin is the adipocyte-specific product of the ob gene. Expression of leptin in fully fed animals reflects adipocyte size and body-fat mass. Leptin signals the status of body energy stores to the brain, where signals emanate to regulate food intake and whole-body energy expenditure. The leptin gene was identified in the leptin-deficient, obese ob/ob mouse by positional cloning techniques. Recently, leptin has been cloned in domestic species including pigs, cattle, and chickens. The leptin receptor has at least five splice variants; the long form of the receptor is primarily expressed in the hypothalamus and is thought to be the predominant signaling isoform. Leptin receptors are members of the cytokine family of receptors and signal via janus-activated kinases (JAK)/signal transducers and activators of transcription (STAT) and mitogen-activated protein kinase (MAPK) pathways. Mutations in the leptin or leptin receptor genes results in morbid obesity, infertility, and insulin resistance in rodents and humans. Leptin regulates food intake and energy expenditure via central and peripheral mechanisms. Leptin receptors are expressed in most tissues, and in vitro evidence suggests that leptin may have direct effects on some tissues such as adipose tissue, the adrenal cortex, and the pancreatic beta-cell. Leptin is thought to influence whole-body glucose homeostasis and insulin action. Studies are underway to determine the role that leptin plays in the biology of domestic animals.


How do ethically competent nurses behave in clinical nursing practice? A qualitative study.
This study explored how ethically competent nurses behave in clinical nursing practice. Nurses' ethical competency is crucial in nursing practice as it promotes patients' safety and quality of care. Using a purposive sampling technique, 20 clinical nurses in South Korea were interviewed via an online video platform. The data were analysed using a thematic analysis based on phenomenological approach. The main theme found among the participating nurses' ethical competency was caring beyond egocentrism, with two subthemes: (1) patient-centred care based on compassion and (2) responsible behaviour based on nursing professionalism. Factors that enabled this included (1) reasonable work conditions, (2) interpersonal relationships, and (3) nurses' rich personal experiences. Nurses' ethical competency depends on how far they can move away from their own egocentrism and act for their clients' benefit, wherein an appropriate workload and warm human relationships with one's colleagues are essential. Nurses should thus receive education on ethics and professionalism and participate in volunteer and leisure activities that cultivate their degree of empathy. Nursing leaders and managers should understand nurses' ethical competency and its enabling factors to devise effective strategies to promote it.


Tissue-specific transcriptional profiles and heterogeneity of natural killer cells and group 1 innate lymphoid cells.
Natural killer (NK) cells and type 1 innate lymphoid cells (ILC1s) are populations of non-T, non-B lymphocytes in peripheral tissues. Although NK and ILC1 subsets have been described, their identification and characteristics remain unclear. We performed single-cell RNA sequencing and CITE-seq to explore NK and ILC1 heterogeneity between tissues. We observed that although NK1 and NK2 subsets are conserved in spleen and liver, ILC1s are heterogeneous across tissues. We identified sets of genes expressed by related subsets or characterizing unique ILC1 populations in each organ. The syndecan-4 appeared as a marker discriminating murine ILC1 from NK cells across organs. Finally, we revealed that the expressions of EOMES, GZMA, IRF8, JAK1, NKG7, PLEK, PRF1, and ZEB2 define NK cells and that IL7R, LTB, and RGS1 differentiate ILC1s from NK cells in mice and humans. Our data constitute an important resource to improve our understanding of NK-ILC1 origin, phenotype, and biology.


Near IR overtone spectral investigations of cyclohexanol using local mode model--evidence for variation of anharmonicity with concentration due to hydrogen bonding.
The near infrared vibrational overtone absorption spectrum of liquid phase cyclohexanol in carbon tetrachloride in different concentrations are examined in the region Deltav=2, 3 and 4. The free and bonded OH local mode mechanical frequency values and anharmonicity values obtained from fitting the overtones are analysed. The observation supports the conclusions drawn from earlier experimental studies on anharmonicity variation of OH-stretching vibrations of alcohols due to intermolecular hydrogen bonding. Our observation is also in agreement with the ab initio calculations on water dimer and trimer. Mechanical anharmonicity of bonded OH-stretching bands tends to increase as a consequence of strong hydrogen bonding at higher concentrations.


The Use of a Small Private Online Course to Allow Educators to Share Teaching Resources Across Diverse Sites: The Future of Psychiatric Case Conferences?
The authors sought to demonstrate the feasibility of integrating small private online course (SPOC) technology with flipped classroom techniques in order to improve neuroscience education across diverse training sites. Post-graduate medical educators used SPOC web conferencing software and video technology to implement an integrated case conference and in-depth neuroscience discussion. Ten psychiatry training programs from across the USA and from two international sites took part in the conference. Feedback from participants was largely positive. This pilot demonstrated the feasibility of such a program and provided a diverse audience with the opportunity to engage in an interactive learning experience with expert faculty discussants. This may be a useful model for programs with limited local expertise to expand their teaching efforts in a wide range of topics.


Adult Neural Stem Cells from the Subventricular Zone Give Rise to Reactive Astrocytes in the Cortex after Stroke.
Reactive astrocytes (RAs) have been reported to convert to multipotent neural stem cells (NSCs) capable of neurosphere (NS) formation and multilineage differentiation in vitro. Using genetic tagging, we determined that subventricular zone (SVZ) NSCs give rise to NSs derived from the stroke-injured cortex. We demonstrate that these cells can be isolated from the cortex in two different models of stroke and from different stroke-lesioned cortical regions. Interestingly, SVZ NSCs give rise to a subpopulation of RAs in the cortex that contribute to astrogliosis and scar formation. Last, we show that these SVZ derived RAs can be converted to neurons in vivo by forced expression of Ascl1. Identifying the contribution of cells originating from the SVZ to injury repair has implications for neural regeneration strategies.


PVA-alginate immobilized cells for anaerobic ammonium oxidation (anammox) process.
The feasibility of an anaerobic ammonium oxidation (anammox) process combined with a cell-immobilization technique for autotrophic nitrogen removal was investigated. Anammox biomass was cultivated from local activated sludge and achieved significant anammox activity in 6 months. The development of a mature anammox biomass was confirmed by fluorescence in situ hybridization (FISH) analysis and off-line activity measurements. The abundance fraction of the anammox bacteria determined by FISH analysis was estimated by software. The anaerobic ammonia oxidizers occupied almost half of the total cells. Additionally, the anammox biomass was granulated as spherical gel beads of 3-4 mm in diameter by using a cell-immobilization technique. The nitrogen removal activity was proved to be successfully retained in the beads, with about 80% of nitrogenous compounds (NH(4) (+), NO(2) (- )and total nitrogen) removed after 48 h. These results offer a promising technique for the preservation of anammox microorganisms, the protection of them against the unfavorable surroundings, and the prevention of biomass washout towards the implementation of sustainable nitrogen elimination biotechnology. This is the first report on the immobilization of anammox biomass as gel beads.


Multilocular cyst of the kidney.
Five cases of multilocular cyst of the kidney are presented with a follow-up of 8 mo to 13 yr. Two children were treated with partial nephrectomy and three with nephrectomy. Radiation therapy and chemotherapy were not given pre- or postoperatively. Ultrasonography is helpful in preoperative diagnosis of this lesion. A brief review of the literature, differential diagnosis, possible etiology, preoperative evaluation and treatment are discussed.


Impact of age and vector construct on striatal and nigral transgene expression.
Therapeutic protein delivery using viral vectors has shown promise in preclinical models of Parkinson's disease (PD) but clinical trial success remains elusive. This may partially be due to a failure to include advanced age as a covariate despite aging being the primary risk factor for PD. We investigated transgene expression following intracerebral injections of recombinant adeno-associated virus pseudotypes 2/2 (rAAV2/2), 2/5 (rAAV2/5), 2/9 (rAAV2/9), and lentivirus (LV) expressing green fluorescent protein (GFP) in aged versus young adult rats. Both rAAV2/2 and rAAV2/5 yielded lower GFP expression following injection to either the aged substantia nigra or striatum. rAAV2/9-mediated GFP expression was deficient in the aged striatonigral system but displayed identical transgene expression between ages in the nigrostriatal system. Young and aged rats displayed equivalent GFP levels following LV injection to the striatonigral system but LV-delivered GFP was deficient in delivering GFP to the aged nigrostriatal system. Notably, age-related transgene expression deficiencies revealed by protein quantitation were poorly predicted by GFP-immunoreactive cell counts. Further, in situ hybridization for the viral CβA promoter revealed surprisingly limited tropism for astrocytes compared to neurons. Our results demonstrate that aging is a critical covariate to consider when designing gene therapy approaches for PD.


Effect of hydrazine based deproteination protocol on bone mineral crystal structure.
In several bone deproteination protocols the chemical agent used for protein cleavage is hydrazine. The effect of hydrazine deproteination method on the crystal size and crystallinity of the bone mineral was studied. Bovine bones were subjected to this protocol and the crystal size and crystallinity of the remaining bone mineral were determined by X-ray Diffraction (XRD), by measuring the width at the half of the maximum intensity of the (002) reflection. It was found that hydrazine deproteination induces noteworthy increase of crystal size and crystallinity. The effect was enhanced by increasing hydrazine temperature from 25 to 55°C. Furthermore, infrared spectroscopy revealed that hydrazine facilitates the removal of carbonate and acid phosphate ions from bone mineral. It is proposed that the mechanism of modification of crystal size and crystallinity lies on the removal of these ions thus, resulting in crystal re-organization.


Coexistent Loss of the Expressions of BRCA1 and p53 Predicts Poor Prognosis in Triple-Negative Breast Cancer.
To investigate the prognostic significance of altered breast cancer susceptibility gene 1 (BRCA1) and p53 expression in triple-negative breast cancer (TNBC). Immunohistochemical expression of BRCA1 and p53 was examined in the tumor tissues of 465 TNBC cases and relations were sought with clinicopathological features and patient survival. Loss of BRCA1 expression was found in 29.5% (137/465) of TNBCs. Positive expression of p53 was observed in 49.9% (232/465). Patients with loss of BRCA1 expression had a tendency to have higher rate of lymph node metastasis (p = 0.075). An association between p53 expression and high histological grade was observed (p = 0.039). TNBC patients with loss of BRCA1 expression had a tendency to have poorer overall survival (OS) than those positive for BRCA1 (p = 0.09). TNBC patients with positive p53 expression showed better OS than those with p53 negativity (p = 0.001). In terms of combined expression patterns, significantly poorer overall survival (OS) was observed for BRCA1-negative/p53-negative TNBCs and best OS for BRCA1-positive/p53-positive TNBCs (p = 0.005). Combined expression patterns of BRCA1 and p53 could serve as useful prognostic markers in TNBC.


Bioactivity of bioresorbable osteosynthetic devices made of hydroxyapatite/poly-DL-lactide composites: an experimental study.
To investigate the bioactivity of the self-designed biodegradable osteosynthetic devices made of resorbable hydroxyapatite microparticles/poly-DL-lactide (HA/PDLLA) composites. Forty-three rabbits with a transverse transcondylar osteotomy of the distal femur were fixed intramedullary by a HA/PDLLA rod, the duration of follow-up were 3, 6, 12, 24 and 36 weeks. Histological, scanning electron microscopic (SEM), energy dispersive X-ray (EDX) and biomechanical analyses were done. Active new bone formation and direct bone-bonding were seen at the bone-implant interface. Generous apatite crystals deposited and grew on the surface of the composites at 3 approximately 6 weeks postoperation. The interfacial shear strength increased significantly. Through the incorporating of resorbable HA microparticles, specific bone-bonding and active osteogenic capacity is introduced. This kind of bioactivity, together with other properties such as sufficient mechanical strength, enhanced biocompatibility and radiopacity, which are intrinsically unobtainable in totally resorbable polymer/polymer systems, make the HA/PDLLA composites become a desirable material for the internal fixation of cancellous bone.


Preprocessing and Quality Control for Whole-Genome Sequences from the Illumina HiSeq X Platform.
The advancement of high-throughput sequencing technologies enables sequencing of human genomes at steadily decreasing costs and increasing quality. Before variants can be analyzed, e.g., in association studies, the raw data obtained from the sequencer need to be preprocessed. These preprocessing steps include the removal of adapters, duplicates, and contaminations, alignment to a reference genome and the postprocessing of the alignment. All later steps, such as variant discovery, rely on high data quality and proper preprocessing, emphasizing the great importance of quality control. This chapter presents a workflow for preprocessing Illumina HiSeq X sequencing data. Code snippets are provided for illustrating all necessary steps, along with a brief description of the tools and underlying methods.


Immunocytochemical characterization of pacinian-like corpuscles in the labia minora of prepubertal girls.
To better understand the precise role of sensory corpuscles within the female external genitalia. After IRB approval, waste tissue samples were obtained from 10 normal girls (aged 2-9 years) who underwent surgery for labial fusion. Immunocytochemistry against protein gene product 9.5 (PGP 9.5), neuron-specific enolase (NSE), vasoactive intestinal peptide (VIP), 5-hydroxytryptamine transporter (5HTT), 5-hydroxytryptamine receptor 1A (5HT1A), Neuronal Peptide Y (NPY), neuronal nitric oxide synthase (nNOS), and estrogen receptors (ER) α and β was performed. Pacinian-like corpuscles were identified in epithelium of labia minora of prepubertal girls. A central structure composed of an axon surrounded by a central core, outer core, external capsule, surrounded by encapsulated stroma, and a subsidiary innervation in the outer aspect of the corpuscle stroma stained for PGP 9.5 in the outer core and layers of the external capsule, NSE positive cells in layers of the outer core, 5HTT in stroma of the corpuscle and cells located in layers of the outer core, 5HT1A in cells of outer core, NPY in stroma of the corpuscle, and nNOS in external core and external capsule of the central structure. ERα was present in stroma, external core, and external capsule, and ERβ in stroma of the corpuscle with subsidiary innervation in the stroma positive to PGP 9.5, VIP, and NPY. PGP 9.5, NSE, ERα, nNOS, and 5HTT immunoreaction detected in the outer core and external capsule could indicate these areas may play an important role in the functional aspects of the Pacinian-like corpuscle.


Management and birth outcomes of pregnant women with Chiari malformations: A 14 years retrospective case series.
The management of Chiari malformations in pregnancy is challenging due to the perceived risk of adverse maternal neurological outcomes and raising intracranial pressure during labour. Our aim was to evaluate the management and health outcomes of pregnant women cared for at a regional referral centre and highlight elements of best practice. A retrospective case series of all pregnant women diagnosed with Chiari malformation over fourteen years (January 2004-June 2018) at the Birmingham Women's Hospital - UK. Twenty-one women (23 pregnancies) with Chiari malformation were included, four had syringomyelia (4/21,19%) and six had previously undergone craniovertebral decompression (6/21, 29%). The median age was 34-years (range 20-41), the median gravidity was two (range 1-8), the median parity was one (range 0-6), and the median extent of tonsillar herniation was 11 mm (range 9-18). The majority of women received their preferred mode of delivery (15 normal vaginal deliveries (15/23, 65.2%) and 6 elective Caesarean sections (6/23, 26.1%)) with two pregnancies ending with an emergency caesarean section for obstetric complications (2/23, 8.7%). Five Caesarean section were performed under general anaesthetic, two under spinal (2/23, 8.7%) and one under epidural anaesthesia (1/23, 4.3%) with no neurological sequelae. There were no adverse neurological outcomes at discharge postnatally. Offering normal vaginal delivery with effective analgesia, for women with Chiari malformation, appears to be safe. Pregnancy care should be provided by a multi-disciplinary team with experience in managing Chiari malformation.


Sensitivity of Escherichia coli to various beta-lactams is determined by the interplay of outer membrane permeability and degradation by periplasmic beta-lactamases: a quantitative predictive treatment.
In Gram-negative bacteria, beta-lactam antibiotics must overcome two barriers, the outer membrane and the periplasmic beta-lactamase, before they reach the targets of their action, penicillin-binding proteins. Although the barrier property of the outer membrane and catalytic property of the beta-lactamases have been studied and their significance in creating beta-lactam resistance emphasized, the interaction between these two barriers has not been treated quantitatively. Such treatment shows that the sensitivity, to a variety of beta-lactams, of the Escherichia coli K-12 cells containing very different levels of chromosomally coded AmpC beta-lactamase, or a plasmid-coded TEM-type beta-lactamase, can be predicted rather accurately from the penetration rate through the outer membrane and the hydrolysis rate in the periplasm. We further propose a new parameter, 'target access index', which is a quantitative expression of the result of interaction between the two barriers, and reflects the probability of success for the antibiotic to reach the targets.


Optimization of soaking conditions (temperature and time) on physicochemical properties of selected parboiled rice varieties grown in Eastern Ethiopia.
This study aimed to optimize soaking temperature and time for better physicochemical properties of parboiled rice varieties grown in Eastern Ethiopia. Two brown rice varieties (NERICA-4 and NERICA-6) were collected from the Somali Regional Agricultural and Pastoral Research Center in Gode. The experiment was designed to aid the design expert software using box-behnken experimental design of response surface methodology to optimize the effects of soaking temperature (60-70°C) and soaking time (4-6 h). Relevant physical and chemical composition properties of the parboiled rice varieties were investigated using standard methods. Numerical optimization of the responses was performed using design expert software. The results showed that soaking time and temperature significantly (p < .05) influenced the physicochemical quality of studied brown rice varieties. The optimal soaking temperature and time were 65°C and 6 h, respectively, for NERICA-4. Under these conditions, the optimum response variables obtained were 375.37 N, 52 min, 12.3%, 1.24%, 13.86%, 2.17%, 3.2942%, 67.1171%, 343.5 kcal/100 g, 274.72 mg/100 g, 318.35 mg/100 g, and 268.31 mg/100 g for hardness, cooking time, moisture, ash, protein, fat, fiber, carbohydrate, energy, magnesium, and potassium and phosphorous content, respectively. However, 65°C and 5 h were optimum soaking temperatures and time for NERICA-6, giving hardness, cooking time, moisture, ash, protein, fat, fiber, carbohydrate, energy content, magnesium, potassium, and phosphorous of 375.18 N, 52 min, 12.2%, 1.4%, 11.54%, 2.29%, 2.89%, 69.6%, 345.42 kcal/100 g, 156 mg/100 g, 105.9 mg/100 g and 136.9 mg/100 g, respectively. The findings showed that rice varieties, in particular NARICA 4, were processed under optimal parboiling conditions in the study setting for better physical properties, proximate composition, and mineral content.


Incorporation of trans-rectal color doppler flow imaging and risk-stratification nomogram reduce unnecessary prostate biopsies in suspected prostate cancer patients: a bi-centered retrospective validation study.
To explore the role of Trans-rectal Color Doppler Flow Imaging (TR-CDFI) and risk-stratification nomogram in a MRI-directed biopsy pathway and examine its clinical performance, via comparisons between existing four biopsy pathways. A Bi-centered retrospective cohort study on biopsy-naïve male population who received ultrasound-guided prostate biopsy from Jan. 2015 to Feb. 2022 was proposed. All enrolled patients should have undergone serum-PSA test, TR-CDFI and multiparametric MRI before biopsy, and subsequently opted for surgical intervention, enabling more accurate pathological grading. We then utilized univariate and multivariate logistic regression analysis to construct a predictive nomogram for risk-stratification. Outcome measurements were overall prostate cancer (PCA) detection rate, clinically significant PCA (csPCA) detection rate, clinically insignificant PCA (cisPCA) detection rate, biopsy avoidance rate and missed csPCA detection rate. Decision curve analysis was used to compare the performances between diagnostic pathways. Under the criteria mentioned above, 752 patients from two centers were included. Reference pathway (biopsy for all) showed that overall PCA detection rate was 46.1%, csPCA and cisPCA detection rates were 32.3% and 13.8% respectively. Risk-based MRI-directed TR-CDFI pathway, which incorporated both TR-CDFI and risk stratification nomogram, exhibited PCA detection rate of 38.7%, csPCA detection rate of 28.7%, cisPCA detection rate of 7.0%, Biopsy avoidance rate of 42.4%, and missed csPCA detection rate of 3.6%. Decision curve analysis revealed that the risk-based pathway held the most net benefit, under the threshold probability level between 0.1 and 0.5. The risk-based MRI-directed TR-CDFI pathway out-performed other strategies, balancing csPCA detection and biopsy avoidance. This suggested that incorporation of TR-CDFI and risk-stratification nomogram in the early PCA diagnostic procedures could reduce unnecessary biopsies.


A study of respiratory function in normal schoolchildren in northern Nigeria.
Respiratory function tests have been performed on schoolchildren in Zaria, Nigeria, to determine normal values among healthy children. Three hundred and eighty-eight students, comprising 257 male and 131 female children, from the Government Day Secondary School were included in this study. The forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), forced mid-expiratory flow (FMF 25-75%) and forced expiratory flow were measured using the vitalograph apparatus. It was observed from the results that the mean values of respiratory function tests in boys were significantly higher (P less than 0.01) than the mean values matched for age, height and weight in female children. It was also observed that the values obtained in the present study were lower than those for Caucasian children. However, it was observed that FVC, FEV1 and FMF 25-75% correlated significantly with age, height, weight and body surface area.


Geographic diversity in Helicobacter pylori oipA genotype between Korean and United States isolates.
Helicobacter pylori outer membrane inflammatory protein A (OipA) was originally named for its role in inducing inflammation in the host, as evidenced by high mucosal IL-8 levels. Expression of OipA is regulated by phase variation of a CT dinucleotide-repeat located in the 5' region of the gene. However, little is known about OipA geographic diversity across isolates. To address this gap, we conducted a large-scale molecular epidemiologic analysis using H. pylori clinical isolates obtained from two geographically distinct populations: Korea and the United States (US). Most Korean isolates (98.7%) possessed two copies of oipA located at two specific loci (A and B) while all US isolates contained only one copy of oipA at locus A. Furthermore, most Korean oipA (94.8%) possessed three or less CT repeats while most US oipA (96.6%) contained five or more CT repeats. Among the two copies, all Korean H. pylori possessed at least one oipA 'on' phase variant while the single copy of oipA in US isolates showed 56.2% 'on' and 43.8% 'off.' Thus, host differences seem to have driven geographic diversification of H. pylori across these populations such that OipA expression in US isolates is still regulated by phase variation with 5 or more CT repeats, while Korean isolates always express OipA; duplication of the oipA combined with a reduction of CT repeats to three or less ensures continued expression. En masse, these findings suggest that diversity in the oipA gene copy number, CT repeats, and phase variation among H. pylori from different populations may confer a benefit in adaptation to particular host populations.


Characterization of ovarian gonadotropin receptor. Monomer and associated form of the receptor.
We have purified luteinizing hormone/human choriogonadotropin (hCG) receptor from rat ovary by sequential affinity column on wheat germ lectin-Sepharose and hCG-Sepharose chromatography. The purified receptor, previously identified as a single protein on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) (Kusuda, S., and Dufau, M.L. (1986) J. Biol. Chem. 261, 16161-16168), was further characterized by radioiodination with 1,3,4,6-tetrachloro-3 alpha, 6 alpha-diphenylglycouril, and column chromatography on wheat germ lectin-Sepharose. Autoradiography of SDS-PAGE analysis under reducing conditions showed a single radiolabeled band of Mr = 80,000. The radioiodinated receptors treated with peptide:N-glycosidase F migrated at Mr = 54,000. Treatment with neuraminidase alone caused only a minor reduction in molecular weight, and subsequent treatment with endo-alpha-N-acetyl-D-galactosaminidase had little further effect on the receptor. When the radioiodinated receptor was analyzed by fast protein liquid chromatography, a single broad peak was eluted with Mr of approximately 350,000. The higher Mr of radioiodinated receptors than that of native receptors (Mr = 190,000 dimeric form) could be due to the aggregation of labeled molecules. These complexes dissociated into the monomeric form in the presence of SDS. To determine whether the monomers can bind hormone, the purified unlabeled receptors resolved with SDS were electroblotted to nitrocellulose membranes and incubated with 125I-hCG. Autoradiograms of the blots showed a band of monomer (Mr = 78,000) as well as one of dimer (Mr approximately 150,000). These studies have demonstrated that the luteinizing hormone/hCG receptors are predominantly N-linked glycosylated and suggest that the native receptor is a dimer of identical hormone binding subunits associated by noncovalent interactions. Although the individual subunits can bind hormone, it is conceivable that the dimeric form is necessary for signal transduction.


An action video clip database rated for familiarity in China and Germany.
Stimulus material for studying object-directed actions is needed in different research contexts, such as action observation, action memory, and imitation. Action items have been generated many times in individual laboratories across the world, but they are used in very few experiments. For future studies in the field, it would be worthwhile to have a larger set of action stimulus material available to a broader research community. Some smaller action databases have already been published, but those often focus on psycholinguistic parameters and static action stimuli. With this article, we introduce an action database with dynamic action stimuli. The database contains action descriptions of 1,754 object-directed actions that have been rated for familiarity in Germany and in China. For 784 of these actions, action video clips are available. With the use of our database, it is possible to identify actions that differ in familiarity between Western and Eastern cultures. This variable may be of interest to some researchers in the field, since it has been shown that familiarity influences action information processing. Action descriptions are listed and categorized in tables that can be downloaded, along with the corresponding video clips, as supplemental material.


Improvement of straw decomposition and rice growth through co-application of straw-decomposing inoculants and ammonium nitrogen fertilizer.
The growth of rice is reduced by the slow decomposition of accumulated straw, which competes with rice for soil nitrogen nutrient. In recent year, straw-decomposing inoculants (SDIs) that can accelerate straw decomposition and ammonium nitrogen (N) fertilizer that can quickly generate available N is increasingly adopted in China. However, it is still unknown whether the N demand of straw decomposition and crop growth can be simultaneously met through the co-application of SDIs and ammonium N fertilizer. In this study, we investigated the effect of the co-application of SDIs and ammonium bicarbonate on decomposition rate of wheat straw, rice growth and rice yield over two consecutive years in rice-wheat rotation system. Compound fertilizer (A0) was used as control. The ratios of ammonium bicarbonate addition were 20% (A2), 30% (A3) and 40% (A4), respectively, without SDIs or with SDIs (IA2, IA3, IA4). Our results revealed that without SDIs, compared with A0, straw decomposition rate, rice growth and yield were improved under A2; However, under A3, rice yield was decreased due to the slow decomposition rate of straw and limited growth of rice during late growth stage. Combining SDIs and N fertilizer increased straw decomposition rate, rice growth rate and yield more than that of N fertilizer alone, especially under IA3. Compared with A0, straw decomposition rate, tiller number, aboveground biomass, leaf area index, root length, and nitrogen use efficiency were significantly increased by 16%, 8%, 27%, 12%, 17%, and 15% under IA3. Consequently, the average rice yield of IA3 was increased to 10,856 kg/ha, which was 13% and 9% higher, respectively, than of A0 and A2. Our results indicated that ammonium bicarbonate application alone carried a risk of nutrient deficiency during late growth stage and yield decline. Therefore, the co-application of SDIs and 30% ammonium N fertilizer substitution can be a favorable practice to simultaneously accelerate straw decomposition and increase rice crop growth.


The physical forces mediating self-association and phase-separation in the C-terminal domain of TDP-43.
The TAR DNA-binding protein of 43kDa (TDP-43) has been identified as the main component of amyotrophic lateral sclerosis (ALS) cytoplasmic inclusions. The link between this proteinopathy and TDP-43's intrinsically disordered C-terminal domain is well known, but recently also, this domain has been shown to be involved in the formation of the membraneless organelles that mediate TDP-43's functions. The mechanisms that underpin the liquid-liquid phase separation (LLPS) of these membraneless organelles undergo remain elusive. Crucially though, these factors may be the key to understanding the delicate balance between TDP-43's physiological and pathological functions. In this study, we used nuclear magnetic resonance spectroscopy and optical methods to demonstrate that an α-helical component in the centre (residues 320-340) of the C-terminal domain is related to the protein's self-association and LLPS. Systematically analysing ALS-related TDP-43 mutants (G298S, M337V, and Q331K) in different buffer conditions at different temperatures, we prove that this phase separation is driven by hydrophobic interactions but is inhibited by electrostatic repulsion. Based on these findings, we rationally introduced a mutant, W334G, and demonstrate that this mutant disrupts LLPS without disturbing this α-helical propensity. This tryptophan may serve as a key residue in this protein's LLPS.


[Hungarian data on inflammatory bowel diseases: analytical data on ulcerative colistis].
Prospective data collection seems to be essential in evidence-based medicine. Because of the new therapeutic options, the need for standard data collection and testing has significantly increased. In Hungary, a registry for patients with inflammatory bowel disease has already been set up, which makes it possible for clinicians to collect prospective data on their patients. Basic characteristics of the database of patients with ulcerative colitis are presented in this paper. The inflammatory bowel disease registry uses the programme of Microsoft Access database management system. Data are stored in a central server. The incidence of inflammatory bowel diseases has been permanently increasing in Hungary; however, its overall prevalence is still low among the European countries. The frequent administration of immunosuppressive medications (azathioprine and corticosteroids) and their increased doses worsen the estimation of the activity. 1., It would be very useful to gain prospective data from all national centres. This kind of database would be able to give a complete picture regarding the Hungarian therapeutical practice. 2., Medications of patients may alter the clinical value of the laboratory findings in the process of determining the severity of the disease.


Novel VEGFR2 inhibitors with thiazoloquinoxaline scaffold targeting hepatocellular carcinoma with lower cardiotoxic impact.
Hepatocellular carcinoma (HCC) is a fatal tumor which is usually diagnosed at advanced stage. Molecular targeted drugs were used recently to treat HCC, however, due to serious side effects, mainly cardiotoxicity and emergence of resistance, there is demanding to explore new chemotherapeutics. 10 novel thiazoloquinoxaline derivatives coupled with different sulfonamide moieties 4(a-j) were designed and synthesized fulfilling pharmacophoric features of VEGFR-2 inhibition. Structures of all new compounds were verified via spectral and microanalytical data. After carrying in-vitro VEGFR-2 assay for compounds 4(a-j); sulfapyridine and sulfamethoxazole derivatives 4d and 4f showed potential inhibitory effect [61.04 and 83.35 nM], respectively, comparable to standard sorafenib [51.41 nM]. Both were then further evaluated for their cytocidal activity against HepG2 cell-line and against myocardium cells using H9C2 cell-line. As a result, only sulfapyridine derivative 4d exhibited a significant inhibition of HepG2 cells viability [IC50 = 4.31 μM]. Furthermore, it showed relatively lower cytotoxic impact against normal H9C2 myocardium cells [IC50, 33.47 μM] compared to that of sorafenib [IC50, 98.07 μM]. In-vivo study was carried out to determine myocardium safety of compound 4d on irradiated mice (8 Gy). In-vivo results of sulfapyridine derivative 4d showed normal cardiac enzyme function (CK) and serum catalase activity with significant reductions in LDH, cardiac TNF-α and caspase-9 levels, alongside with its efficacy in suppressing the expression of hepatic VEGF. In conclusion, sulfapyridine derivative 4d could be considered a promising candidate as VEGFR-2 inhibitor with less myocardium side effect.