Synthesis of an active hybrid growth factor (GF) in bacteria: transforming GF-alpha/vaccinia GF fusion protein.
A hybrid gene encoding for a polypeptide consisting of the first 33 N-terminal amino acid (aa) residues of transforming growth factor-alpha (TGF-alpha) and a C terminus consisting of 20 aa residues of vaccinia growth factor (VGF) was chemically synthesized and expressed as a fusion protein in Escherichia coli. The primary structure of the hybrid gene product maintained the same positioning of the three disulfide bonds found in each parent molecule thus conserving the first two loop regions of TGF-alpha and the third loop region of VGF. After cleavage with CNBr its renatured biological activity was found to be comparable to TGF-alpha and VGF with respect to binding to the epidermal growth factor receptor, stimulation of DNA synthesis and induction of anchorage-independent growth of NRK cells in the presence of TGF-beta. Thus, we suggest that similar domains can be interchanged within the same family of molecules and equivalent functionality maintained.


Use of 2-Octyl-Cyanoacrylate in surgical closing of Postparotidectomy salivary fistulas.
A salivary fistula is one of possible postoperative complications in the surgery of parotid gland tumors. We present three cases of postparotidectomy salivary fistulas, successfully treated by surgical access using 2-octyl-cyanoacrylate while closing the skin layer. The previous treatment of these cases by other therapeutic options did not give satisfactory results. In a 5-year follow-up period there were no signs of fistulas relapses. The surgical access with use of 2-octyl cyanoacrylate can be one of therapeutic options for the closing of postparotidectomy salivary fistulas, especially in cases where other therapeutic accesses are not successful.


Friction and morphology of pleural mesothelia.
To verify the hypothesis that by enmeshing lubricants, microvilli reduce the coefficient of kinetic friction (μ) of pleural mesothelium, μ was measured during reciprocating sliding of rabbit's visceral against parietal pleura before and after addition of hyaluronan, and related to the morphological features of the microvillar network. Because no relation was found between μ or μ changes after hyaluronan and microvillar characteristics, the latter are not determinants of the frictional forces which oppose sliding of normal mesothelial surfaces under physiological conditions, nor of the effects of hyaluronan. Addition of hyaluronan increased μ slightly but significantly in normal specimens, probably by altering the physiological mix of lubricants, but decreased μ of damaged mesothelia, suggesting protective, anti-abrasion properties. Indeed, while sliding of an injured against a normal pleura heavily damaged the latter and increased μ when Ringer was interposed between the surfaces, both effects were limited or prevented when hyaluronan was interposed between the injured and normal pleura before onset of sliding.


Medication versus trauma-focused psychotherapy for adults with posttraumatic stress disorder: A systematic review and meta-analysis.
The goal of this study was to summarize evidence from head-to-head randomized trials for treatment of posttraumatic stress disorder (PTSD) in adults comparing trauma-focused psychotherapies and selective serotonin reuptake inhibitors (SSRIs) or serotonin/norepinephrine reuptake inhibitors (SNRIs) in a systematic review and meta-analysis. We conducted a search of multiple databases to identify trials comparing a trauma-focused psychotherapy (cognitive behavioral therapy, prolonged exposure, cognitive therapy, cognitive processing therapy or eye movement desensitization and reprocessing) to an SSRI or SNRI. Cochrane Risk of Bias 2.0 was used to assess risk of bias; high risk of bias trials were included only in sensitivity analyses. PTSD symptom reduction was the primary outcome. Four trials met inclusion criteria. Random effects meta-analysis of the two trials that were not high risk of bias showed no difference in PTSD symptom reduction, but a wide confidence interval, including effects favoring psychotherapy and effects favoring medication. Heterogeneity was high. Inclusion of the two high risk of bias trials did not change substantive conclusions. There is insufficient evidence to determine whether SSRIs or trauma-focused psychotherapies are more effective for PTSD symptom reduction among adults with PTSD.


Examining weekly relationships between obsessive-compulsive and eating disorder symptoms.
Despite the severity and high rate of co-occurrence between eating disorders (ED) and obsessive-compulsive disorder (OCD), less is known regarding the longitudinal sequencing of their comorbidity and whether and how their symptoms may influence one another over time. The current study sought to answer these questions by testing if a bidirectional, longitudinal relationship exists between ED symptoms and OCD obsessions and compulsions. We examined the relationship between ED symptoms, obsessions and compulsions across five time points, each one week apart using auto-regressive cross-lagged panel modeling. The final sample consisted of 358 individuals from the community with moderate levels of ED and OCD symptoms, the majority of whom identified as White and male. Bivariate correlations revealed that ED symptoms, obsessions and compulsions were associated with one another across the five weeks. Two cross-lagged panel models indicated that ED symptoms predicted OCD symptoms at numerous time points and vice versa. However, we found this significant longitudinal associations across only certain weeks. Notably, the models found that only ED symptoms and OCD obsessions predicted one another across different time points across the five weeks; ED symptoms and OCD compulsions did not predict one another. Due to the non-clinical nature of the sample, there is limited generalizability to clinical populations. Our results provide preliminary evidence that there is a bidirectional, longitudinal relationship between ED symptoms and OCD symptoms among a community sample, particularly with respect to cognitive as opposed to behavioral symptoms.


Correlations between spin equilibrium shift, reduction rate, and N-demethylation activity in liver microsomal cytochrome P-450 and a series of benzphetamine analogues as substrates.
Cytochrome P-450 forms a thermal ferric spin equilibrium which is significantly shifted by substrate binding. Within a series of benzphetamine analogues the liver microsomal enzyme system exhibits a close correlation of the substrate induced spin equilibrium shift towards the high spin state and both the rate of P-450 reduction, and of substrate turnover, as well. The spin equilibrium regulates the first electron transfer by favoured high spin state reduction and rapid pre-equilibration with respect to the low spin fraction.


Quantitative elemental mapping of biological tissues by laser-induced breakdown spectroscopy using matrix recognition.
The present study demonstrates the importance of converting signal intensity maps of organic tissues collected by laser-induced breakdown spectroscopy (LIBS) to elemental concentration maps and also proposes a methodology based on machine learning for its execution. The proposed methodology employs matrix-matched external calibration supported by a pixel-by-pixel automatic matrix (tissue type) recognition performed by linear discriminant analysis of the spatially resolved LIBS hyperspectral data set. On a swine (porcine) brain sample, we successfully performed this matrix recognition with an accuracy of 98% for the grey and white matter and we converted a LIBS intensity map of a tissue sample to a correct concentration map for the elements Na, K and Mg. Found concentrations in the grey and white matter agreed the element concentrations published in the literature and our reference measurements. Our results revealed that the actual concentration distribution in tissues can be quite different from what is suggested by the LIBS signal intensity map, therefore this conversion is always suggested to be performed if an accurate concentration distribution is to be assessed.


Intensifying the saturation biopsy technique for detecting prostate cancer after previous negative biopsies: a step in the wrong direction.
To report the results using an extensive saturation biopsy in men with negative prostate biopsies but in whom there is still a clinical suspicion for carcinoma. Between February 1999 and October 2004 we offered 40 patients (median age 63 years) an extensive saturation biopsy if there was clinical suspicion of prostate cancer after previous negative prostate biopsies. The median (range) number of cores taken was 64 (39-139) and was adjusted to the size of the prostate. All patients received general or spinal anaesthesia. Of the 40 patients, 18 (45%) had carcinoma in at least one core; 16 had a radical prostatectomy, which showed pT2a, pT2b, pT2c, pT3a and pT3b adenocarcinoma of the prostate in three, four, six, two and one patients, respectively. Brachytherapy and external radiation were the therapies of choice in the other patients. Sixteen patients had marked haematuria after the biopsy procedure. There is no significant increase in the cancer detection rate in an extensive saturation-biopsy regimen compared to published series with fewer cores, but the morbidity increased.


Dimorphic expression of sex-related genes in different gonadal development stages of sterlet, Acipenser ruthenus, a primitive fish species.
Molecular mechanism of sex determination and differentiation of sturgeon, a primitive fish species, is extraordinarily important due to the valuable caviar; however, it is still poorly known. The present work aimed to identify the major genes involved in regulating gonadal development of sterlet, a small species of sturgeon, from 13 candidate genes which have been shown to relate to gonadal differentiation and development in other teleost fish. The sex and gonadal development of sterlets were determined by histological observation and levels of sex steroids testosterone (T), 11-ketotestosterone (11-KT), and 17β-estradiol (E2) in serum. Sexually dimorphic gene expressions were investigated. The results revealed that gonadal development were asynchronous in 2-year-old male and female sterlets with the testes in early or mid-spermatogenesis and the ovaries in chromatin nucleolus stage or perinucleolus stage, respectively. The levels of T and E2 were not significantly different between sexes or different gonadal development stages while 11-KT had the higher level in mid-spermatogenesis testis stage. In all the investigated gonadal development stages, gene dmrt1 and hsd11b2 were expressed higher in male whereas foxl2 and cyp19a1 were expressed higher in female. Thus, these genes provided the promising markers for sex identification of sterlet. It was unexpected that dkk1 and dax1 had significantly higher expression in ovarian perinucleolus stage than in ovarian chromatin nucleolus stage and in the testis, suggesting that these two genes had more correlation with ovarian development than with the testis, contrary to the previous reports in other vertebrates. Testicular development-related genes (gsdf and amh) and estrogen receptor genes (era and erb) differentially expressed at different testis or ovary development stages, but their expressions were not absolutely significantly different in male and female, depending on the gonadal development stage. Expression of androgen receptor gene ar or rspo, which was supposed to be related to ovarian development, presented no difference between gonadal development stages investigated in this study whenever in male or female.


Can categorical knowledge be used in visual search?
Smith, Redford, Gent, and Washburn (2005) have proposed a new categorization paradigm called the visual-search categorization task to study how display size affects categorization performance. Their results show that, in a wide range of conditions, category knowledge collapses as soon as multiple stimuli are simultaneously displayed in a scene. This result is surprising and important considering that humans parse and categorize objects from complex scenes on a daily basis. However, Smith et al. only studied one kind of category structure. This article presents the results of three experiments exploring the effect of display size on perceptual categorization as a function of category structure. We show that rule-based and information-integration categories are differently affected by display size in the visual search categorization task. For rule-based structures, target-present and target-absent trials are not much affected by display size. However, the effect of display size is bigger for information-integration category structures, and much more pronounced for target-absent trials than for target-present trials. A follow-up experiment shows that target redundancy (i.e., having more than one target in the display) does not improve performance with information-integration category structures. These results suggest that categories may be learned differently depending on their underlying structure, and that the resulting category representation may influence performance in the visual search categorization task.


Lipopolysaccharide intracerebral administration induces minimal inflammatory reaction in rat brain.
An inflammatory reaction, essential for defence against infection and for wound repair, may also induce irreversible tissue damage. It appears that the central nervous system has developed its own immunosuppressive strategy in order to limit the destructive effects of inflammation. To clarify this point, we have characterized in one unique model of inflammation induced in the rat by intracerebral lipopolysaccharide injection the kinetics of the inflammatory reaction, the participation of immunitary and glial cells and of three growth factors. Among these molecules, brain-derived neurotrophic factor mRNA expression was found decreased following LPS injection. No striking differences were observed in the brain parenchyma after stab lesion or inflammatory lesion apart from an increase in the number of monocytes/macrophages recruited early to the lesion area. Macrophages were later accumulated around the lesion when astroglia and microglia reactions occurred. Some of the macrophages and microglia expressed major histocompatibility complex class II antigens on their surface whereas no T or B lymphocytes were observed in the brain parenchyma. However, a subpopulation of CD3- and CD4-negative CD8-positive cells, likely natural killer cells, was observed around the lesion site; this recruitment was inhibited by the highest dose of LPS. This study therefore supports the hypothesis of a suppression of some aspects of cell-mediated immunity in the brain, mechanisms which need to be further characterized.


Development of cardiac sympathetic and adrenal-medullary responses in borderline hypertensive rats.
Borderline hypertensive (BHR) rats are the first generation offspring of a cross of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats. In adulthood, BHRs have systolic blood pressures in the 140-160 mm Hg range. If subjected to chronic stress paradigms, however, BHRs develop sustained and permanent elevations in systolic blood pressure (180-200 mm Hg). In the present study, we examined the functional development of cardiac and adrenal medullary responses to reflex activation of the sympathetic nervous system in preweanling BHR and WKY rats. Pups of the two groups were injected with insulin or saline at 4, 8, 12, or 16 days of age and sacrificed 3 h later. Insulin produces an acute lowering of blood glucose which is attended by a centrally mediated increase in sympathetic activity. The induction of ornithine decarboxylase (ODC) activity in heart and the depletion of epinephrine from the adrenal medulla were biochemical indicators of functional sympathetic neurotransmission. WKY and BHR pups had similar levels of cardiac ODC activity under basal conditions and following administration of insulin. In contrast, BHRs had higher amounts of adrenal norepinephrine and epinephrine from 4 to 16 days of age and greater depletion of adrenal epinephrine following insulin administration at 8, 12 and 16 days of age. These findings indicate that BHRs have a greater capacity for catecholamine biosynthesis, storage and release in the adrenal medulla during the preweanling period compared to age-matched normotensive WKY controls. This alteration in the adrenal medulla during the preweanling period may contribute to the susceptibility of adult BHR rats to stress-induced hypertension.


Hematopoietic stem cell gene therapy with drug resistance genes: an update.
Transfer of drug resistance genes into hematopoietic stem cells (HSCs) has promise for the treatment of a variety of inherited, that is, X-linked severe combined immune deficiency, adenosine deaminase deficiency, thalassemia, and acquired disorders, that is, breast cancer, lymphomas, brain tumors, and testicular cancer. Drug resistance genes are transferred into HSCs either for providing myeloprotection against chemotherapy-induced myelosuppression or for selecting HSCs that are concomitantly transduced with another gene for correction of an inherited disorder. In this review, we describe ongoing experimental approaches, observations from clinical trials, and safety concerns related to the drug resistance gene transfer.


Acute Hemodynamic Effects of Sacubitril-Valsartan In Heart Failure Patients Receiving Intravenous Vasodilator and Inotropic Therapy.
Prior study has demonstrated that transitioning patients in acutely decompensated heart failure with a low cardiac output directly from intravenous (i.v.) vasoactive (ie, vasodilators or inotropes) drugs to sacubitril-valsartan (S/V) can be done safely with tolerance to the 1-month follow-up. Here, we further characterize the hemodynamic impact of S/V after patients have been optimized on vasoactive therapy. In a single-center, retrospective analysis, 25 patients with cardiac index of less than 2.2 L/min/m2 were admitted to the cardiac intensive care unit and newly initiated on angiotensin receptor-neprilysin inhibitor therapy with the guidance of invasive hemodynamic monitoring. Hemodynamic data were gathered and compared upon cardiac intensive care unit admission, after optimization with i.v. vasoactive therapy, and after S/V initiation and weaning off i.v. All patients who tolerated S/V (n = 20) were weaned off vasoactive medications before transfer out of cardiac intensive care unit. Patients maintained their significant improvement in cardiac index and reduction in SVR/PVR on transition from i.v. inotropic and vasodilator therapy to oral S/V. There was an increase in pulmonary artery pulsatility index with S/V therapy compared with the i.v. vasoactive phase of care. Patients in the cardiac intensive care unit can be successfully bridged from vasoactive i.v. therapy to oral S/V with sustained improvement in cardiac index garnered from vasoactive agents. We also observed improvement in the pulmonary artery pulsatility index and maintenance of left and right ventricular unloading with S/V. These encouraging findings merit further prospective study.


The effect of two retraining programs, barefoot running vs increasing cadence, on kinematic parameters: A randomized controlled trial.
The aim of this study was to compare the effects of two 10-week non-laboratory-based running retraining programs on foot kinematics and spatiotemporal parameters in recreational runners. One hundred and three recreational runners (30 ± 7.2 years old, 39% females) were randomly assigned to either: a barefoot retraining group (BAR) with 3 sessions/week over 10 weeks, a cadence retraining group (CAD) who increased cadence by 10% again with 3 sessions/week over 10 weeks and a control group (CON) who did not perform any retraining. The footstrike pattern, footstrike angle (FSA), and spatial-temporal variables at comfortable and high speeds were measured using 2D/3D photogrammetry and a floor-based photocell system. A 3 × 2 ANOVA was used to compare between the groups and 2 time points. The FSA significantly reduced at the comfortable speed by 5.81° for BAR (p < 0.001; Cohen's d = 0.749) and 4.81° for CAD (p = 0.002; Cohen's d = 0.638), and at high speed by 6.54° for BAR (p < 0.001; Cohen's d = 0.753) and by 4.71° for CAD (p = 0.001; Cohen's d = 0.623). The cadence significantly increased by 2% in the CAD group (p = 0.015; Cohen's d = 0.344) at comfortable speed and the BAR group showed a 1.7% increase at high speed. BAR and CAD retraining programs showed a moderate effect for reducing FSA and rearfoot prevalence, and a small effect for increasing cadence. Both offer low-cost and feasible tools for gait modification within recreational runners in clinical scenarios.


Successful treatment with famciclovir for varicella zoster virus infection resistant to acyclovir.
Varicella zoster virus (VZV) reactivates more frequently in immunocompromised patients than immunocompetent subjects and is a significant cause of morbidity and mortality. Acyclovir is frequently used for treatment against VZV reactivation. However, long-term use of acyclovir can result in the emergence of VZV strain resistant to acyclovir. Here, we report a 67-year-old man with adult T-cell leukemia who suffered from herpes zoster with acyclovir-resistant VZV after long-term prophylaxis. The isolated viruses from his skin lesions were a mixture of acyclovir-resistant and acyclovir-susceptible strains. Sequence analysis showed the presence of thymidine kinase (TK) mutations in the resistant clones. Interestingly, oral administration of famciclovir, a prodrug form of penciclovir, resulted in resolution of his herpes zoster, although most acyclovir-resistant strains of VZV were reported to be resistant to penciclovir. This implied that a certain amount of susceptible VZV with wild-type viral TK gene was present in vivo, and that famciclovir could be phosphorylated intracellularly by the intact viral kinases. As famciclovir is more potent and longer-acting than acyclovir, the susceptible strains might have suppressed the generation and proliferation of the resistant in vivo. Even when VZV is developing resistance to acyclovir, famciclovir might be effective at least in the early resistant phase.


Tracheostomy: Experience at Tertiary Hospital.
An attempt was made to find indications of tracheostomy procedure and its complications in the modern era of medicine with refined surgical techniques at a tertiary hospital. A retrospective study of 240 patients, who had undergone tracheostomy, was done during the period from January 2013 to April 2017 at Govt. Medical College Hospital. Various details of all participants such as age and sex of patients, detailed history of the current disease, and detailed information about tracheostomy and complications were recorded. In the present study, the most common indication for tracheostomy was prolonged ventilation due to Organophosphorus poisoning and Snake bite. The complication rate for tracheostomy procedure was 11.5%. The most common complication was tubal occlusion (7.5%) followed by Granulations around stoma (2.5%), Tracheal stenosis (1.25%), tracheoesophageal fistula (0.4%). No death was occurred during the tracheostomy procedure. The morbidity and mortality due to tracheostomy are reduced definitely. Tracheostomy Complications can be prevented by refined surgical techniques, use of high volume low pressure cuffed tracheostomy tubes and attentive post-operative nursing care. Yet complications of tracheomalacia and tracheal stenosis call for further improvement.


Acute kidney injury in 2011: Biomarkers are transforming our understanding of AKI.
Acute kidney injury (AKI) is a syndrome of decreased renal function that is associated with an increased risk of death. Studies from 2011, particularly in the field of AKI biomarkers, have provided important insights into the diagnosis, prognosis, and treatment of AKI. These advances are now being brought to the bedside to improve diagnosis and treatment of AKI.


[Analysis of the articles published in Chinese journal of ophthalmology during years 2001 to 2004].
To study characteristics of the publication of Chinese Journal of Ophthalmology during years of 2001 to 2004. Statistic method was used to retrieve the following parameters of Chinese Journal of Ophthalmology: numbers of articles, columns, citation frequencies, grants support, time lag from accepted to publication. The journal published 926 pieces of papers and 16 reports during years of 2001 to 2004. There were 24 columns; citation rates were 89.98%; papers published in the journal 19.53% got grant support. The times lag for publication was relatively longer. Chinese Journal of Ophthalmology is a high quality, specialized and core periodical in china.


Capillary electrophoresis-integrated immobilized enzyme microreactor with graphene oxide as support: Immobilization of negatively charged L-lactate dehydrogenase via hydrophobic interactions.
We report the first application of hydrophobic interaction between graphene oxide (GO) and negatively charged enzymes to fabricate CE-integrated immobilized enzyme microreactors (IMERs) by a simple and reliable immobilization procedure based on layer by layer assembly. L-lactate dehydrogenase (L-LDH), which is negatively charged during the enzymatic reaction, is selected as the model enzyme. Various spectroscopic techniques, including SEM, FTIR, and UV-vis are used to characterize the fabricated CE-IMERs, demonstrating the successful immobilization of enzymes on the negatively charged GO layer in the capillary surface. The IMER exhibits excellent repeatability with RSDs of inter-day and batch-to-batch less than 3.49 and 6.37%, respectively, and the activity of immobilized enzymes remains about 90% after five-day usage. The measured Km values of pyruvate and NADH of the immobilized L-LDH are in good agreement with those obtained by free enzymes. The results demonstrate that the hydrophobic interactions and/or π-π stacking is significant between the GO backbone and the aromatic residues of L-LDH and favorable to fabrication of CE-integrated IMERs. Finally, the method is successfully applied to the determination of pyruvate in beer samples.


Antegrade or Retrograde Cerebral Perfusion in Ascending Aorta and Hemiarch Surgery? A Propensity-Matched Analysis.
Over the years, numerous options have been proposed for surgical management of ascending aorta and aortic arch pathology in an attempt to minimize postoperative morbidity and probability of death. We present a propensity score-matching analysis of 259 patients from a single unit who were operated on under deep hypothermic arrest with retrograde cerebral perfusion (DHCA/RCP) or moderate hypothermic circulatory arrest with selective antegrade cerebral perfusion (via common carotid artery) (MHCA/ACP). Between 2006 and 2014 a total of 259 consecutive patients underwent ascending aorta and hemiarch correction under HCA. DHCA/RCP and MHCA/ACP were performed on 207 and 52 patients, respectively. Baseline patient characteristics accounted for in the propensity matching were age, sex, acute aortic dissection, emergency operation, re-operation, preoperative hemodynamic instability, preoperative kidney injury, and CA time. After propensity scoring 40 pairs (80 patients) were successfully matched (p = 0.732). Outcomes were defined as the incidence of postoperative neurologic complications, 30-day mortality, and all-cause midterm mortality. Surgical procedure that involved the MHCA/ACP technique was associated with 76.5% decreased risk (risk ratio, 0.235; 95% CI, 0.079 to 0.699) of postoperative neurologic complications (p = 0.009). In addition to MHCA/ACP in surgical procedure for acute aortic dissection a relevant trend was established for 30-day mortality (risk ratio, 0.333; 95% CI, 0.09 to 1.23). For midterm all-cause mortality, MHCA/ACP modestly decreased the number of deaths (p = 0.0456) in comparison with the DHCA/RCP technique. MHCA/ACP in aortic arch surgical procedure is associated with a decreased risk of all types of neurologic complications and a trend toward decreased 30-day and midterm mortality in comparison with DHCA/RCP.


Computed tomography features and clinicopathological characteristics of gastric glomus tumor.
Gastric glomus tumor (GGT) is a rare neoplasm that is difficult to distinguish from other gastric submucosal tumors due to a lack of diagnostic experience. The goal of this study was to better understand GGT by looking at its clinicopathological features, computed tomography (CT) features, and differential diagnosis. The clinical data and CT findings of 21 pathologically confirmed GGT patients were examined. The clinical characteristics and CT findings of benign GGT were compared to gastric stromal tumors (GST) (n = 30) and heterotopic pancreas (n = 30). The 21 cases included six males and fifteen females ranging in age from 42 to 64 years. The lesions were found in the gastric body in four cases and the antrum in seventeen. GGT was diagnosed as benign in 20 cases and malignant in one. In benign cases, the glomus cells were small, uniform, showed perivascular hemangiopericytoma‑like or solid nest‑like structures. Obvious mitotic figures were observed in the malignant case. SMA staining was positive in the tumor cells. A quasi-round or round solid mass protruded into the gastric cavity in 20 benign cases, with a clear and smooth edge. The long to short diameter ratio was 1.01 ± 0.15. All of the benign cases had obvious enhancement, with homogeneous enhancement in ten cases and heterogeneous enhancement in ten cases, as well as central filling enhancement in 12 cases. The ratio of CT value of lesion to abdominal aorta in arterial phase and venous phase were (0.41 ± 0.11) and (0.81 ± 0.20), which were significantly higher than GST and heterotopic pancreas. The irregular mass broke through the gastric wall and invaded liver with poorly defined boundary and internal necrosis, heterogeneous persistent moderate enhancement with thickening blood supply arteries was seen in one malignant case with a long diameter of 150 mm and a thick diameter of 30 mm. CT enhancement usually shows persistent obvious enhancement, especially in arterial phase, which provides important value for the diagnosis. CT findings can help in the differential diagnosis of GGT and other submucosal tumors.


Interaction of alkylputrescines with ornithine decarboxylase from rat liver and Escherichia coli: an in vitro and in vivo study.
The inhibitory effect of a series of 2-alkylputrescines on rat liver and Escherichia coli ornithine decarboxylase (L-ornithine carboxy-lyase, EC 184.108.40.206) was examined. At 2.5 mM concentrations, 2-methyl-, 2-propyl-, 2-butyl-, 2-pentyl- and 2-hexylputrescines were stronger inhibitors of the mammalian enzyme than putrescine. Only the higher homologues (from 2-propyl- to 2-hexylputrescine) were inhibitors of the E. coli enzyme. An analysis of the effect of increasing concentrations of the 2-alkylputrescines showed that the main difference in the behaviour of the mammalian and E. coli decarboxylases toward 2-alkylputrescines was that the former was strongly inhibited by 2-methylputrescine whereas the latter was not. 2-Alkylputrescines were found to be competitive inhibitors of both the bacterial and mammalian enzyme. The smallest Ki values (0.1 and 0.5 mM) were found for the 2-hexyl- and 2-pentylputresciens. N-Methyl-, N-ethyl-, N-propyl- and N-butylputrescines (50 mumol per 100 g body weight) were assayed as inhibitors of thioacetamide-induced rat liver ornithine decarboxylase. N-Propylputrescine was found to be the most inhibitory (66% inhibition) and although the N-alkylputrescines were taken up by the liver, they did not inhibit the liver polyamine pools. Both putrescine and N-methylputrescine were found to stabilize the thioacetamide-induced ornithine decarboxylase at the onset of the enzyme's degradation, while 2-alkylputrescines were inhibitory under similar conditions. N-Methylputrescine induced antizyme in thioacetamide-treated rats. In thioacetamide- or dexamethasone-treated rats, 2-methylputrescine was found to be the strongest in vivo inhibitor of the liver decarboxylase. Although 2-alkylputrescines were efficiently taken up by the liver, they did not noticeably inhibit its polyamine pools. 2-methylputrescine decreased the putrescine concentration of the liver, but not its spermidine and spermine content. No induction of ornithine decarboxylase antizyme by 2-methylputrescine could be detected. The intrahepatic concentration of the latter decreased with time, very likely due to its degradation by a diamine oxidase, since the decrease was inhibited by aminoguanidine.


Ginkobiloba extract improves working memory performance in middle-aged women: role of asymmetry of prefrontal cortex activity during a working memory task.
In order to clarify the mechanism through which extract of Ginkgo biloba leaves (EGb) improves cognitive function, we examined the effects of EGb on cerebral blood oxygenation in the prefrontal cortex (PFC) and on performance during a working memory task, using near-infrared spectrometry (NIRS). First, we evaluated differences in behavioral performance of the Sternberg working memory test (ST) and in the activation pattern of the PFC during ST between 15 young and 19 middle-aged healthy women. Then, we examined the effect of EGb (120 mg/day for 6 weeks) on ST performance and PFC activation pattern in the middle-aged group. The middle-aged group exhibited a longer reaction time (RT) in ST than the young group and showed a different PFC activation pattern during ST, i.e., the middle-aged group showed bilateral activation while the young group showed right-dominant activation. In the middle-aged group, administration of EGb for 6 weeks shortened the RT of ST and changed the PFC activation pattern to right-dominant, like that in the young group. The results indicate the PFC plays a role in the physiological cognitive function-enhancing effect of EGb. EGb might improve working memory function in middle-aged individuals by counteracting the occurrence of aging-related hemispheric asymmetry reduction.


Legacy effects of simulated short-term climate change on ammonia oxidisers, denitrifiers, and nitrous oxide emissions in an acid soil.
Although the effect of simulated climate change on nitrous oxide (N2O) emissions and on associated microbial communities has been reported, it is not well understood if these effects are short-lived or long-lasting. Here, we conducted a field study to determine the interactive effects of simulated warmer and drier conditions on nitrifier and denitrifier communities and N2O emissions in an acidic soil and the longevity of the effects. A warmer (+2.3 °C) and drier climate (-7.4% soil moisture content) was created with greenhouses. The variation of microbial population abundance and community structure of ammonia-oxidizing archaea (AOA), bacteria (AOB), and denitrifiers (nirK/S, nosZ) were determined using real-time PCR and high-throughput sequencing. The results showed that the simulated warmer and drier conditions under the greenhouse following urea application significantly increased N2O emissions. There was also a moderate legacy effect on the N2O emissions when the greenhouses were removed in the urea treatment, although this effect only lasted a short period of time (about 60 days). The simulated climate change conditions changed the composition of AOA with the species affiliated to marine group 1.1a-associated lineage increasing significantly. The abundance of all the functional denitrifier genes decreased significantly under the simulated climate change conditions and the legacy effect, after the removal of greenhouses, significantly increased the abundance of AOB, AOA (mainly the species affiliated to marine group 1.1a-associated lineage), and nirK and nosZ genes in the urea-treated soil. In general, the effect of the simulated climate change was short-lived, with the denitrifier communities being able to return to ambient levels after a period of adaptation to ambient conditions. Therefore, the legacy effect of simulated short-time climate change conditions on the ammonia oxidizer and denitrifier communities and N2O emissions were temporary and once the conditions were removed, the microbial communities were able to adapt to the ambient conditions.


Dust deposition mechanism and output characteristics of solar bifacial PV panels.
The utilization of solar photovoltaic (PV) power generation represents a highly promising technological solution for addressing environmental challenges and energy crises. Dust deposition on the front and back surfaces of solar bifacial PV panels greatly decreases the optical performance and power generation. In this study, the dust deposition characteristics and mechanism of solar bifacial PV panels are investigated using the CFD-DEM method. The effects of the dust deposition rate on the output characteristics of bifacial PV panels are discussed. The research results show that the particle deposition behaviors on the back and front surfaces of bifacial PV panels are influenced by the deposition and separation forces at the left or right inlets. The dust deposition rate of windward surfaces can be 1.48-7.60 times that of the leeward surfaces of bifacial PV panels. The particle motion trajectories on the windward and leeward sides can be mainly divided into five and three kinds, respectively. The dust deposition rate of bifacial PV panels increases when the air inlet velocity decreases and the particle size and concentration and relative humidity increase. The open circuit voltage and short circuit current of bifacial PV panels decreased by 26.7% and 16.4%, respectively, when the dust deposition rate increases by 45.8%. The attenuation rate of the maximum output power of PV panels has a positive linear correlation with the dust deposition rate, as shown in Eq. 22. The bifacial PV panels have better output characteristics than the mono-facial PV panels with consideration of dust deposition.


Microcephaly.
True microcephaly (head circumference ≤-3SD), either primary (present at birth) or secondary (of postnatal onset) results from an imbalance between progenitor cell production and cell death that lead to a reduced number of neuronal and glial cells within the brain, resulting in reduced brain growth. Primary non-syndromal microcephalies are recessive disorders resulting from abnormal control of mitotic spindle and cell cycle kinetics in progenitor cells. Microcephaly is also a frequent sign of defects in DNA double- and/or single-strand break repair and in nucleotide excision repair, in which it often is associated with general growth impairment. In these etiologies, cognitive functions are reasonably well preserved despite severe reduction in brain volume. Neuronal migration defects are often associated with secondary microcephaly, as are anomalies of telencephalic cleavage. Secondary microcephalies are often associated with increased neuronal death, and can be associated with metabolic disorders such as serine deficiency or thiamine pyrophosphate transporter deficiency. Microcephaly can be associated with hundreds of syndromal congenital anomalies, including many chromosomal disorders. Genetic etiologies of developmental microcephalies are reviewed.


Muscle artifacts in multichannel EEG: characteristics and reduction.
To study the characteristics of unintentional muscle activities in clinical EEG, and to develop a high-throughput method to reduce them for better revealing drug or biological effects on EEG. Two clinical EEG datasets are involved. Pure muscle signals are extracted from EEG using Independent Component Analysis (ICA) for studying their characteristics. A high-throughput method called ICA-SR is introduced based on a new feature named Spectral Ratio (SR). The spectral and temporal characteristics of the muscle artifacts are illustrated using representative muscle signals. The spatial characteristics are presented at both the group- and the subject-level, and are consistent under three different electrode reference methodologies. Objectively compared with an existing method, ICA-SR is shown to reduce more artifacts, while introduce less distortion to EEG. Its effectiveness is further demonstrated in real clinical EEG with the help of a CO(2)-inhalation EEG recording session. The characteristics of unintentional muscle activities align with the reported characteristics of controlled muscle activities. Artifact spatial characteristics can be EEG equipment dependent. The ICA-SR method can effectively and efficiently process clinical EEG. Armed with advanced signal processing algorithms, this study expands our knowledge of muscle activities in EEG from muscle-controlled experiments to general clinical trials. The ICA-SR method provides an urgently needed solution with validated performance for efficiently processing large volumes of clinical EEG.


Bacteriologic evidence of infection caused by coagulase-negative staphylococci in total hip replacement.
Coagulase-negative staphylococci are important agents of infected hip arthroplasties, but sample contamination from the skin flora may confuse the diagnosis. Recovery of multiple identical strains has been regarded as indication of true infection. We have evaluated 29 total hip replacement operations with cultures positive for coagulase-negative staphylococci in a prospective study, 16 with > or = 3 isolates available for strain identity analysis. In 26 episodes, > or = 3 cultures were positive for coagulase-negative staphylococci, but only 19 of them had strong or intermediate clinical evidence of infection. Negative clinical evidence of infection coincided with the absence of a predominating strain according to plasmid profile analysis. A reliable identity analysis may help to rule out infection when multiple cultures are positive in patients who lack clinical evidence of infection.


Comparison of different methods of obturator nerve block in transurethral resection of bladder tumors: A systematic review and network meta-analysis.
Bladder cancer is the most common malignancy of the urinary system, and accounts for 3% of newly diagnosed tumors. Transurethral resection of bladder tumor plays a key role in treating bladder cancer, among which one of the most serious complications is bladder perforation caused by obturator nerve reflex. Obturator nerve reflex can be prevented by inducing obturator nerve block after lumbar anesthesia. However, No study so far has compared the inhibitory effect of different obturator nerve block approaches on intraoperative obturator nerve reflex and bladder perforation. In this study, we conducted a network meta-analysis (NMA) of studies comparing the efficacy of different obturator nerve block approaches performed after lumbar anesthesia in operation. The distal obturator nerve block guided by peripheral nerve stimulator is the best approach for preventing obturator reflex. The proximal obturator nerve block guided by ultrasound is the best approach for preventing bladder perforation. Spinal anesthesia combined with the distal obturator nerve block guided by peripheral nerve stimulator is the most optimal approach to prevent the obturator nerve reflex. But the doctor should choose the appropriate anesthesia method according to the patient's general condition, tumor location, and doctor's proficiency in puncture techniques.


An insulin-responsive element in the pancreatic enhancer of the amylase gene.
We have identified a distinct insulin-responsive element (IRE) located within the pancreatic enhancer of the mouse amylase gene Amy-2.2. A 30-base pair (bp) fragment was previously shown to be sufficient to transfer insulin response to a heterologous promoter. The 30-bp fragment overlaps the tissue-specific pancreatic enhancer that binds the putative transcriptional activator PTF1. To determine whether enhancer and IRE activities could be separated, we introduced three 10-base pair substitutions into the 30-bp region. The mutated regulatory regions were cloned upstream of a heterologous promoter and transferred to transgenic mice. Mutants 1 and 2 retained PTF1 binding activity and insulin response. Mutant 3 retained PTF1 binding, but was defective in insulin response. The results indicate that the IRE is functionally distinct from the PTF1-binding site, although the two overlap physically. In contrast to the wild-type gene, mutant 3 is characterized by constitutive expression in diabetic animals, suggesting that a binding site for a repressor has been destroyed. A nuclear protein with affinity for the IRE was detected in normal and diabetic pancreas. This protein does not bind mutant 3, suggesting that it may be involved in negative regulation of amylase in diabetic pancreas.


Prolonged survival with unresected pulmonary metastases.
The cases of 3 selected patients who had prolonged survival with pulmonary metastases that doubled in size yearly are reported. The experience with these patients and another, whose disease rapidly progressed after resection of pulmonary metastases, admonishes that the selection criteria for resection of pulmonary metastases require further refinement.


Type I collagen degradation product in serum of patients with early rheumatoid arthritis: relationship to disease activity and radiological progression in a 3-year follow-up.
The new assay of cross-linked carboxyterminal telopeptide of type I collagen (ICTP), a serum marker for bone collagen degradation, was evaluated in serial measurements of 66 patients with early RA during a 3-yr prospective study. Initially 51% of RA patients had elevated levels of serum ICTP compared to healthy controls. During the subsequent months after starting anti-rheumatic treatment, the mean ICTP levels decreased in parallel with the clinical and laboratory variables measuring disease activity. Despite marked clinical improvement with anti-rheumatic treatment, a steady increase in radiological progression of joints was observed. Throughout the follow-up serum ICTP levels correlated with inflammatory parameters and from the first year on with the radiological changes assessed annually. However, initial serum ICTP levels correlated better than the other variables of disease activity with the subsequent erosive progression of joints indicating that measurement of serum ICTP may serve as one of the prognostic markers for joint damage in early RA.


The Effects of Spark-Plasma Sintering (SPS) on the Microstructure and Mechanical Properties of BaTiO₃/3Y-TZP Composites.
Composite ceramics BaTiO₃/3Y-TZP containing 0 mol %, 3 mol %, 5 mol %, 7 mol %, and 10 mol % BaTiO₃ have been prepared by conventional sintering and spark-plasma sintering (SPS), respectively. Analysis of the XRD patterns and Raman spectra reveal that the phase composition of t-ZrO₂, m-ZrO₂, and BaTiO₃ has been obtained. Our results indicate that SPS can be effective for the decrease in grain size and porosity compared with conventional sintering, which results in a lower concentration of m-ZrO₂ and residual stress. Therefore, the fracture toughness is enhanced by the BaTiO₃ phase through the SPS technique, while the behavior was impaired by the piezoelectric second phase through conventional sintering.


[INERTIA study: Clinical inertia in non-insulinized patients on oral hypoglycemic treatment. A study in Spanish primary and specialty care settings].
To study clinical inertia in the management of oral hypoglycemic agents (OHA) in non-insulin treated patients with type 2 diabetes mellitus (T2DM) in Spain. Epidemiological, cross-sectional, retrospective (2 years), multicenter study. Clinical inertia was measured as the total number of patients without OHA treatment intensification divided by the total number of patients with inadequate HbA1c values (≥7%), multiplied by 100. Total clinical inertia (TCI) was the absence of OHA treatment intensification in all visits with a HbA1c≥7% values in the previous 2 years; partial clinical inertia (PCI) occurred when this absence only occurred in some of these visits. We assessed OHA treatment compliance with the Morisky-Green test. We included 2,971 patients, 1,416 adequately controlled (HbA1c<7%) and 1,555 inadequately controlled (HbA1c≥7%). PCI prevalence was 52.5%(95% confidence interval [95% CI] 52.4-52.6%) while TCI prevalence was 12.8% (95% CI 12.2-13.8%). PCI was lower in patients adequately controlled as compared with those inadequately controlled (31.4% vs. 71.8%; P<.001). PCI was associated with sedentary lifestyle, hypertension and higher prevalence of micro and macrovascular complications. Only 38.0% of patients were compliant with the OHA treatment, being this percentage even lower in subjects with ICP. Two variables were independently associated with ICP: female sex (odds ratio [OR] 1.43; 95% CI 1.09-1.86%) and a shorter duration of DM2 (OR 0.98; 95% CI 0.95-0.99). One out of 2 patients with T2DM and treated with OHA without insulin suffer from PCI. Only 4 out of 10 patients are compliant with OHA treatment. Female sex and a shorter duration of T2DM are independently associated with PCI.


Ultrastructural evidence of the ion-transporting role of the adult and larval neck organ of the marine gymnomeran Cladocera (Crustacea, Branchiopoda).
The neck organ of adult and immature forms of four marine gymnomeran Cladocera species (Podonidae) has been characterized morphologically by light-scanning- and electron microscopy. Although displaying some special features, a comparison with organs assuming a comparable regulating function in other organisms indicates that the neck organ of the adult Podonidae exhibits ultrastructural evidence of involvement in ion-transporting mechanisms. The extensive ventral plasma membrane infoldings closely connected with the chondriom and the peculiar organization of the cuticular site associated with the subjacent apical cell limits of the organ are among the chief structural specializations. The fact that similar structures are already present in the embryonic neck organ confirms previous indirect evidence that podonid embryos can hypo-osmoregulate as soon as the ion concentration of the brood chamber rises to that of the outside medium.


Effects of serotonergic compounds on aqueous humor dynamics in monkeys.
The effects of several serotonergic agonists on aqueous humor formation (AHF), total outflow facility (OF) and intraocular pressure (IOP) were investigated in living cynomolgus monkeys. We determined the effect of a single topical unilateral 300 microg or 3 mg dose of the 5-HT agonists serotonin, 5-carboxamidotryptamine (5-CT), sumatripan, gepirone, and 8-hydroxy-2(di-n-propylaminotetralin) (8-OH-DPAT) and a 450 microg dose of flesinoxan on IOP (Goldmann applanation tonometry), AHF (scanning ocular fluorophotometry) and total OF (8-OH-DPAT only, topically and intracamerally). Serotonin, 5-CT, sumatripan or gepirone had no significant effect on IOP or AHF. 8-OH-DPAT caused an AHF increase of approximately 70% over 6 hr in both ipsilateral drug- and contralateral vehicle-treated eyes, but no significant change in IOP compared with baseline measured on a separate occasion in the same animals. 8-OH-DPAT did not increase protein levels or rate of entry of systemically administered fluorescein in the anterior chamber aqueous humor compared to historic controls, and no difference was seen between ipsilateral and contralateral eyes. Flesinoxan had no effect on IOP and produced an insignificant 25% increase in flow in treated eyes compared to baseline. The results for 8-OH-DPAT and possibly flexinoxan indicate the presence of a secretion-stimulating 5-HT1A receptor in monkey ciliary epithelium that has little effect on IOP. OF was unchanged following 8-OH-DPAT administered topically or following intracameral exchange.


Temperature-dependent development and emergence pattern of Hypothenemus hampei (Coleoptera: Curculionidae: Scolytinae) from coffee berries.
The coffee berry borer, Hypothenemus hampei (Ferrari) (Coleoptera: Curculionidae: Scolytinae), is the most important constrain for coffee production throughout the world. Knowledge on the emergence pattern of H. hampei females to infest new berries is crucial to effectively plan control measures. In this laboratory study, we assessed the development of immature stages and the emergence pattern of H. hampei females from the berries by exposing them to temperatures that are typical for high-altitude plantations (> or = 1,700 m above sea level [masl] ) or when coffee is grown under shade trees (20-22 degrees C), and optimum altitude plantations (1,200-1,600 masl) or nonshaded coffee (25-30 degrees C). Fecundity and emergence pattern of H. hampei females from coffee berries varied with temperature. Temperature played a crucial role determining the rate of H. hampei development and therefore the emergence of the females to start a new infestation cycle. The emergence and colonization phases of new colonizing females in coffee plantations with mean temperatures of 20, 25, or 30 degrees C would take place at different moments in the development of the coffee berries, and in some cases more than once. The implications of our findings for an improved, site-specific timing of control interventions against H. hampei are discussed.


Species differences in behavioural effects of rolipram and other adenosine cyclic 3H, 5H-monophosphate phosphodiesterase inhibitors.
The effect of the phosphodiesterase (PDE) inhibitors rolipram, Ro 20-1724 and isobutylmethylxanthine (IBMX) on motor behaviour and rectal temperature was studied in mice, rats and guinea pigs following intraperitoneal administration (0.39 to 25 mg/kg). The selective adenosine cyclic 3',5'-monophosphate (cAMP) PDE inhibitors rolipram and Ro 20-1724 in each species caused a dissimilar pattern of neurotropic effects: Hypothermia and hypokinesia in mice, hypothermia, hypokinesia and head twitches in rats, hypothermia, hyperkinesia and head twitches in guinea pigs. The head twitches were associated with forepaw shaking and increased grooming. Rolipram was the most potent compound in the three species. In guinea pigs it was less active than in rats or mice. Ro 20-1724 was approx. 15 to 30 times less potent in inducing the characteristic alterations in the various species. The alkylxanthine PDE inhibitor IBMX, 0.39 to 6.25 mg/kg, slightly stimulated the locomotor activity of mice and rats, most probably due to antagonism of central adenosine actions. IBMX, 6.25 to 25 mg/kg, caused a pattern of neurotropic effects identical to that produced by the selective cAMP PDE inhibitors, indicating the prevalence of the cAMP PDE inhibitory action over the adenosine antagonistic action at higher dosages. IBMX was approx. as potent as Ro 20-1724 in this respect. The species differences in the neurotropic responses to cAMP PDE inhibition in vivo presumably reflect similar differences in the extent of cAMP accumulation in brain tissue of the three species in vitro. Enhanced availability of brain cAMP in vivo in the various rodent species seems to be correlated with diverse patterns of more or less complex motor behavioural symptoms.


Peptide fragments of the heavy-chain region of phosphorylated and dinitrophenylated gizzard myosin.
Sulfopropyl (SP) Sephadex chromatography of trypsin-pepsin digests of dinitrophenylated gizzard myosin, pretreated with and without the myosin light-chain kinase calcium-calmodulin phosphorylating system, yielded similar elution patterns and nine peptide fractions were found. From a comparison with trypsin-pepsin digests of the heavy chains of dinitrophenylated myosin, pretreated with and without the phosphorylating system, it was established that peptide I, a major peptide fraction, was part of the 17-kDa dinitrophenylated light chain. Phosphorylation of myosin did not change the dinitrophenyl group content of peptide I but it did result in a significant increase in the dinitrophenylation of other peptides. The peptides contained only S-dinitrophenyl cysteine. Peptide III, previously considered to be part of the light-chain region (Bailin, G. and Lopez, F. (1982) J. Biol. Chem. 257, 264-270), was shown to originate in the heavy chains of myosin based on a comparison of the elution patterns of the digests of modified myosin and its heavy chains. Several neutral and basic peptides (peptides III to IX) originated in the heavy-chain region and they were different from those from the heavy chains of rabbit skeletal myosin. Phosphorylation of the 20-kDa light chain shifted the dinitrophenylation of the sulfhydryl groups from the 17-kDa light chain to the heavy chains of myosin, predominantly. These thiol groups do not resemble the fast-reacting -SH groups of rabbit skeletal myosin. The light chains are involved, in part, in making sites available on myosin that are necessary for actin-myosin interaction.


Point and interval estimation of primary and secondary parameters in a two-stage adaptive clinical trial.
Investigated in this paper is the point estimation and confidence intervals of the treatment efficacy parameter and related secondary parameters in a two-stage adaptive trial. Based on the minimal sufficient statistics, several alternative estimators to the sample averages are proposed to reduce the bias and to improve the precision of estimation. Confidence intervals are constructed using Woodroofe's pivot method. Numerical studies are conducted to evaluate the bias and mean squared error of the estimators and the coverage probability of the confidence intervals.


Kaempferol tri- and tetrasaccharides from Camellia japonica seed cake and their inhibitory activities against matrix metalloproteinase-1 secretion using human dermal fibroblasts.
Eight kaempferol oligosaccharides were isolated and identified from Camellia japonica seed cake. The chemical structures of the isolates were determined by using chromatographic and spectroscopic techniques, such as high-performance liquid chromatography with a photodiode array detector (HPLC-PDA), one-dimensional (1H and 13C), and two-dimensional nuclear magnetic resonance (1H-1H COSY, HSQC and HMBC), ESI-Q-TOF-MS, and optical rotation. To evaluate the anti-aging efficacy of kaempferol oligosaccharides for cosmetic use, the MMP-1 inhibitory effects of the isolates were studied using human dermal fibroblasts which were cultured in HaCaT cell-conditioned media. The MMP-1 inhibitory assay results revealed that kaempferol-3-O-β-d-xylopyranosyl-(1 → 3)-α-l-rhamnopyranosyl-(1 → 6)-O-β-d-glucopyranosyl-(1 → 2)-O-β-d-glucopyranoside showed the most potent MMP-1 inhibitory activity. The basal level inhibition was 50 ppm, which indicated that C. japonica seed cake is a promising material for the development of anti-aging skin cosmetics.


Upgraded D22 SEC-SANS setup dedicated to the biology community.
Described here is the current status of the upgraded in situ size-exclusion chromatography (SEC) system implemented with the D22 small-angle neutron scattering (SANS) instrument at the Institut Laue-Langevin. Since its initial proof of principle in 2016, this SEC-SANS arrangement has been continuously requested by the user community, leading to the design of an upgraded version. A detailed description of the setup and its control is provided, and a few examples of protein structural investigations are presented, which will highlight the various possibilities and limitations of the setup to optimize experimental success.


Cancer, viruses and environmental factors.
The genesis of Burkitt's lymphoma is visualized as proceeding in three steps: I. Primary EBV infection affects the young child, probably at a relatively high multiplicity. It immortalizes a certain number of B-lymphocytes in vivo. II. This is followed by the impact of an environmental promoting agent, perhaps chronic holoendemic malaria, providing a chronic stimulus to the proliferation of the EBV-carrying preneoplastic cells. III. Chromosomally abnormal variants appear in the stimulated tissue by chance. After certain types of changes, particularly the 8 to 14 translocation that leads to the 14q+ marker, the affected B lymphocyte would no longer obey the negative feedback controls that would otherwise restrict its proliferation in vivo.


Solid phase synthesis of a biased mini tetrapeptoid-library for the discovery of monodentate ITAM mimics as ZAP-70 inhibitors.
The biased library was composed of a novel phosphotyrosine mimic fixed in the P1 position of a tetrapeptoid and combined with three lipophilic N-substituents at the remaining positions giving a total of 27 single compounds. Screening for ZAP-70 antagonism identified 8 as a novel selective monodentate ZAP-70 antagonist and lead in the search for new immunosuppressive drugs.


Activation of PPARα by bezafibrate negatively affects de novo synthesis of sphingolipids in regenerating rat liver.
Serine palmitoyltransferase (SPT) is a key enzyme in de novo sphingolipid biosynthesis. SPT activity in liver is up-regulated by pro-inflammatory cytokines, which play an important role in initiation of liver regeneration after partial hepatectomy (PH). The aim of the study was to investigate the impact of a high-fat diet or PPARα activation by bezafibrate on the activity and protein expression of SPT in rat liver after PH. The animals were divided into three groups: those fed a standard chow (SD), those fed a high-fat diet (HFD), and those treated with bezafibrate (BF). It has been found that the expression and activity of SPT increased in regenerating liver. This was accompanied by the elevation of plasma NEFA concentration. Moreover, in both diet groups, the content of sphinganine increased. Bezafibrate decreased protein expression of SPT at the 4th and 12th hour, and inhibited SPT activity at the 4th hour after PH. Both, the plasma NEFA concentration and sphinganine content decreased in the groups treated with bezafibrate. We conclude that partial hepatectomy stimulates de novo sphingolipid synthesis. Activation of PPARα by bezafibrate negatively affects this process, presumably by decreasing the availability of plasma-borne fatty acids.


Testicular biodistribution of 450 nm fluorescent latex particles after intramuscular injection in mice.
The significant expansion in the use of nanoparticles and submicron particles during the last 20 years has led to increasing concern about their potential toxicity to humans and particularly their impact on male fertility. Currently, an insufficient number of studies have focused on the testicular biodistribution of particles. The aim of our study was to assess the distribution of 450 nm fluorescent particles in mouse testes after intramuscular injection. To this end, testes were removed from 5 groups of 3 mice each at 1 h (H1), 4 days (D4), 21 days (D21), 45 days (D45) and 90 days (D90) after the injection of 7.28 × 10⁹ particles in the tibialis anterior muscles of each mouse. We examined histological sections from these samples by epifluorescence microscopy and confocal microscopy and identified testicular biodistribution of a small number of particles in groups H1, D4, D21, D45 and D90. Using CD11b immunostaining, we showed that particles were not carried into the testis by macrophages. The intratesticular repartition of particles mainly followed testicular vascularization. Finally, we found some particles in seminiferous tubules but could not determine if the blood-testis barrier was crossed.


Synthesis of active-site rich molybdenum-doped manganese tungstate nanocubes for effective electrochemical sensing of the antiviral drug (COVID-19) nitazoxanide.
Nitazoxanide (NTZ), a promising antiviral agent, is currently being tested in clinical trials as a potential treatment for novel coronavirus disease 2019 (COVID -19). This paper describes a one-pot hydrothermal synthesis to prepare molybdenum (Mo)-doped manganese tungstate nanocubes (Mo-MnWO4 NCs) for the electrochemical sensing of NTZ. The as-prepared Mo-MnWO4 NCs were characterized using various techniques such as XRD, Raman, FE-SEM, FE-TEM, and XPS to confirm the crystal structure, morphology, and elemental composition. The obtained results demonstrate that Mo doping on MnWO4 generates many vacancy sites, exhibiting remarkable electrochemical activity. The kinetic parameters of the electrode modified with Mo-MnWO4 NCs were calculated to be (Ks) 1.1 × 10-2 cm2 s-1 and (α) 0.97, respectively. Moreover, a novel electrochemical sensor using Mo-MnWO4 NCs was fabricated to detect NTZ, which is used as a primary antibiotic to control COVID-19. Under optimal conditions, the electrochemical reduction of NTZ was determined with a low detection limit of 3.7 nM for a linear range of 0.014-170.2 μM with a high sensitivity of 0.78 μA μM-1 cm-2 and negligible interference with other nitro group-containing drugs, cations, and anions. The electrochemical sensor was successfully used to detect NTZ in the blood serum and urine samples and achieved high recoveries in the range of 94-99.2% and 95.3-99.6%, respectively. This work opens a way to develop high-performance sensing materials by exploring the introduction of defect engineering on metal tungstates to detect drug molecules for practical applications.


Correlative microscopy: providing new understanding in the biomedical and plant sciences.
Correlative microscopy is the application of two or more distinct microscopy techniques to the same region of a sample, generating complementary morphological, structural and chemical information that exceeds what is possible with any single technique. As a variety of complementary microscopy approaches rather than a specific type of instrument, correlative microscopy has blossomed in recent years as researchers have recognised that it is particularly suited to address the intricate questions of the modern biological sciences. Specialised technical developments in sample preparation, imaging methods, visualisation and data analysis have also accelerated the uptake of correlative approaches. In light of these advances, this critical review takes the reader on a journey through recent developments in, and applications of, correlative microscopy, examining its impact in biomedical research and in the field of plant science. This twin emphasis gives a unique perspective into use of correlative microscopy in fields that often advance independently, and highlights the lessons that can be learned from both fields for the future of this important area of research.


The electrolytic conductivity detector as an element-selective gas chromatographic detector.
The response and elemental selectivity of the electrolytic conductivity detector (E1CD) to nitrogen-, chlorine-, and sulfur-containing compounds has been investigated as a function of chemical structure, furnace chemistry conditions (i.e., reaction gas, furnace temperature, catalyst, and post-furnace chemical abstractors), and solubilization-and-ionization processes (electrolytic chemistry and electrolytic conductance). The "profiling" of detector response for the gas-liquid chromatographic-E1CD analysis of selected compounds under defined furnace chemistry reaction conditions and electrolytic chemistry included the determination of detector signal to noise ratio, peak tailing, and elemental selectivity. Detector response and conductivity phenomena are discussed in terms of gas-phase furnace chemistry reactions, post-furnace reaction or abstraction processes, and solution-phase ionization and neutralization processes occurring in the conductivity cell.


The binding of bicarbonate ions to washed chloroplast grana.
Radioactive labelling techniques show that isolated broken chloroplasts can take up HCO3-in the dark. There are two pools of binding sites for this ion on, or within, the thylakoid membranes. A smaller, high affinity pool exists at a concentration of one HCO3-bound per 380-400 chlorophyll molecules. Removal of HCO3-bound in this pool requires special conditions and results in greater than 90% inhibition of oxygen evolution. The inhibition is fully reversed when HCO3-is added back. HCO3-bound in the small pool does not necessarily exchange with free HCO3-in the dark or in light. Evidence presented suggests that this site is very near the site of action of 3-(3,4-dichlorophenyl)-1,1-dimethyl urea. A second, much larger, pool of HCO3-binding sites also exists in a concentration approaching that of the bulk chlorophyll. These sites have a much lower affinity for HCO3-, and their function has not yet been determined.


Simultaneous construction of vagina and rectum in a patient with absence of both.
This 5-year-old girl was born without a vagina or rectum. Both structures were created from colon using posterior sagittal and abdominal-perineal operative approaches.


Comparative proteome analysis of Helicobacter pylori clinical strains by two-dimensional gel electrophoresis.
To investigate the pathogenic properties of Helicobacter pylori by comparing the proteome map of H. pylori clinical strains. Two wild-type H. pylori strains, YN8 (isolated from biopsy tissue of a gastric cancer patient) and YN14 (isolated from biopsy tissue of a gastritis and duodenal ulcer patient), were used. Proteomic analysis, using a pH range of 3-10 and 5-8, was performed. The individual proteins were identified by quadrupole time-of-flight (Q-TOF) mass spectrometer and protein database search. Variation in spot patterns directed towards differential protein expression levels was observed between the strains. The gel revealed prominent proteins with several protein "families". The comparison of protein expressions of the two strains reveals a high variability. Differentially present or absent spots were observed. Nine differentially expressed protein spots identified by Q-TOF included adenosine triphosphate (ATP)-binding protein, disulfide oxidoreductase B (DsbB)-like protein, N utilization substance A (NusA), ATP-dependent protease binding subunit/heat shock protein, hydantoin utilization protein A, seryl-tRNA synthetase, molybdenum ABC transporter ModD, and hypothetical proteins. This study suggests that H. pylori strains express/repress protein variation, not only in terms of the virulence proteins, but also in terms of physiological proteins, when they infect a human host. The difference of protein expression levels between H. pylori strains isolated from gastric cancer and gastritis may be the initiator of inflammation, and result in the different clinical presentation. In this preliminary study, we report seven differential proteins between strains, with molecule weights from approximately 10 kDa to approximately 40 kDa. Further studies are needed to investigate those proteins and their function associated with H. pylori colonization and adaptation to host environment stress.


The tumor inflammation signature (TIS) is associated with anti-PD-1 treatment benefit in the CERTIM pan-cancer cohort.
The 18-gene tumor inflammation signature (TIS) is a clinical research assay that enriches for clinical benefit to immune checkpoint blockade. We evaluated its ability to predict clinical benefit of immunotherapy in cancer patients treated with PD-1 checkpoint inhibitors in routine clinical care. The CERTIM cohort is a prospective cohort which includes patients receiving immune checkpoint inhibitors in Cochin University hospital. RNA extracted from 58 archival formalin fixed paraffin embedded tumor blocks (including 38 lung cancers, 5 melanomas, 10 renal carcinomas, 4 urothelial carcinomas and 1 colon carcinoma) was hybridized to a beta version of the NanoString® PanCancer IO360™ CodeSet using nCounter® technology. Gene expression signatures were correlated with tumor responses (by RECIST criteria) and overall survival. PD-L1 immunostaining on tumor cells was assessed in 37 non-small cell lung cancer (NSCLC) samples and tumor mutational burden (TMB) measured by whole exome sequencing in 19 of these. TIS scores were significantly associated with complete or partial response to anti-PD-1 treatment in the whole cohort (odds ratio = 2.64, 95% CI [1.4; 6.0], p = 0.008), as well as in the NSCLC population (odds ratio = 3.27, 95% CI [1.2; 11.6], p = 0.03). Patients whose tumor had a high TIS score (upper tertile) showed prolonged overall survival compared to patients whose tumor had lower TIS scores, both in the whole cohort (hazard ratio = 0.37, 95% CI [0.18, 0.76], p = 0.005) and in the NSCLC population (hazard ratio = 0.36, 95% CI [0.14, 0.90], p = 0.02). In the latter, the TIS score was independent from either PD-L1 staining on tumor cells (spearman coefficient 0.2) and TMB (spearman coefficient - 0.2). These results indicate that validated gene expression assay measuring the level of tumor microenvironment inflammation such as TIS, are accurate and independent predictive biomarkers and can be easily implemented in the clinical practice.


Global rainfall erosivity database (GloREDa) and monthly R-factor data at 1 km spatial resolution.
Here, we present and release the Global Rainfall Erosivity Database (GloREDa), a multi-source platform containing rainfall erosivity values for almost 4000 stations globally. The database was compiled through a global collaboration between a network of researchers, meteorological services and environmental organisations from 65 countries. GloREDa is the first open access database of rainfall erosivity (R-factor) based on hourly and sub-hourly rainfall records at a global scale. This database is now stored and accessible for download in the long-term European Soil Data Centre (ESDAC) repository of the European Commission's Joint Research Centre. This will ensure the further development of the database with insertions of new records, maintenance of the data and provision of a helpdesk. In addition to the annual erosivity data, this release also includes the mean monthly erosivity data for 94% of the GloREDa stations. Based on these mean monthly R-factor values, we predict the global monthly erosivity datasets at 1 km resolution using the ensemble machine learning approach (ML) as implemented in the mlr package for R. The produced monthly raster data (GeoTIFF format) may be useful for soil erosion prediction modelling, sediment distribution analysis, climate change predictions, flood, and natural disaster assessments and can be valuable inputs for Land and Earth Systems modelling.


The impact of lifecourse socio-economic position and individual social mobility on breast cancer risk.
Women with an advantaged socioeconomic position (SEP) have a higher risk of developing breast cancer (BC). The reasons for this association do not seem to be limited to reproductive factors and remain to be understood. We aimed to investigate the impact of lifecourse SEP from childhood and social mobility on the risk of BC considering a broad set of potential mediators. We used a discovery-replication strategy in two European prospective cohorts, E3N (N = 83,436) and EPIC-Italy (N = 20,530). In E3N, 7877 women were diagnosed with BC during a median 24.4 years of follow-up, while in EPIC-Italy, 893 BC cases were diagnosed within 15.1 years. Hazard ratios (HR) were estimated using Cox proportional hazard models on imputed data. In E3N, women with higher education had a higher risk of BC (HR [95%CI] = 1.21 [1.12, 1.30]). This association was attenuated by adjusting for reproductive factors, in particular age at first childbirth (HR[95%CI] = 1.13 [1.04, 1.22]). Health behaviours, anthropometric variables, and BC screening had a weaker effect on the association. Women who remained in a stable advantaged SEP had a higher risk of BC (HR [95%CI] = 1.24 [1.07; 1.43]) attenuated after adjustment for potential mediators (HR [95%CI] = 1.13 [0.98; 1.31]). These results were replicated in EPIC-Italy. These results confirm the important role of reproductive factors in the social gradient in BC risk, which does not appear to be fully explained by the large set of potential mediators, including cancer screening, suggesting that further research is needed to identify additional mechanisms.


The proliferation and function of human mononuclear leukocytes and natural killer cells in serum-free medium.
We recently developed a serum-free (SF) culture medium that supports the growth of several established lymphoid cell lines. In an effort to develop a standardized medium for assay of human natural killer (NK) cell activity, we compared the cytotoxic activity of peripheral blood mononuclear leukocytes (PBL) and purified large granular lymphocytes (LGL) cultured in SF medium containing interleukin 2 (IL-2) or medium containing 10% fetal bovine serum (FBS) plus IL-2. The results indicated that PBL had a 30% increase in cumulative net cell growth and had as high or higher cytotoxic activity after growth in SF medium than in medium containing FBS. Purified LGL had a 50% increase in cumulative net cell growth and persisted approximately 2 weeks longer in culture in medium containing FBS than in SF medium. However, the cytotoxic activity of cells grown in SF medium persisted during the initial 3 weeks of culture. Purified LGL that were maintained and were subcultured at cell densities of 10(6) cells or greater per milliliter of either SF or FBS-containing medium had equivalent levels of cytotoxicity over a 44-day period in either medium compared with cells subcultured at a density of 5 X 10(5) cells per milliliter of medium. NK cells produced a cytotoxic factor (NKCF) in SF medium, and its cytotoxic activity was blocked by 10% FBS. We conclude that the SF medium supplemented with IL-2 can be used as an alternative to FBS-containing medium with IL-2 for the growth of NK cells and is advantageous for the production of NKCF.


Oxytocin Receptor Expression in Hair Follicle Stem Cells: A Promising Model for Biological and Therapeutic Discovery in Neuropsychiatric Disorders.
The intricate nature of the human brain and the limitations of existing model systems to study molecular and cellular causes of neuropsychiatric disorders represent a major challenge for basic research. The promising progress in patient-derived stem cell technology and in our knowledge on the role of the brain oxytocin (OXT) system in health and disease offer new possibilities in that direction. In this study, the rat hair follicle stem cells (HFSCs) were isolated and expanded in vitro. The expression of oxytocin receptors (OXTR) was evaluated in these cells. The cellular viability was assessed 12 h post stimulation with OXT. The activation of OXTR-coupled intracellular signaling cascades, following OXT treatment was determined. Also, the influence of OXT on neurite outgrowth and cytoskeletal rearrangement were defined. The assessment of OXTR protein expression revealed this receptor is expressed abundantly in HFSCs. As evidenced by the cell viability assay, no adverse or cytotoxic effects were detected following 12 h treatment with different concentrations of OXT. Moreover, OXTR stimulation by OXT resulted in ERK1/2, CREB, and eEF2 activation, neurite length alterations, and cytoskeletal rearrangements that reveal the functionality of this receptor in HFSCs. Here, we introduced the rat HFSCs as an easy-to-obtain stem cell model that express functional OXTR. This cell-based model can contribute to our understanding of the progression and treatment of neuropsychiatric disorders with oxytocinergic system deficiency.


Silencing of B7H4 Represses the Development of Oral Squamous Cell Carcinoma Through Promotion of M1 Macrophage Polarization.
Tumor-associated macrophages can support oral squamous cell carcinoma (OSCC) progression, and overexpression of the immunomodulator B7H4 correlates with poor prognosis of OSCC patients. We performed this study to assess the effect of B7H4 silencing on macrophage polarization and explore the potential mechanism of B7H4 during OSCC progression. Short hairpin RNA targeting B7H4 was used to knock down B7H4. The predictor variable was B7H4 expression level, and the outcome variables were SCC9 cell growth and metastasis, M1/M2 macrophage ratio, and anti-programmed death-1 (PD-1)/STAT3 pathway-related protein levels. These were measured through real-time qPCR, Western blot analysis, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine assay, and transwell assay. In addition, a tumor xenograft mouse model was used to examine the effect of B7H4 silencing (+/- Colivelin, an activator of STAT3) on tumor growth and macrophage polarization. The expression of B7H4 in OSCC cell lines was more than 2-fold compared with that in human normal oral keratinocytes via real-time qPCR and Western blot analysis. Knockdown of B7H4 repressed the proliferation, migration, and invasion of SCC9 cells, which were detected by 5-ethynyl-2'-deoxyuridine and transwell assay, as well as reduced PD-1/STAT3 pathway-related protein levels, promoted M1 macrophage polarization, and inhibited M2 polarization. In vivo research demonstrated that B7H4 silencing also inhibited the growth of tumor xenograft and increased the M1/M2 ratio in an OSCC mouse model. Colivelin reversed the inhibitory effects of B7H4 knockdown on OSCC progression and reversed macrophage polarization both in vitro and in vivo. B7H4 is upregulated during OSCC progression. Its downregulation may promote M1 macrophage polarization and inhibit M2 macrophage polarization via deactivating the PD-1/STAT3 pathway, thus restraining OSCC development.


Influence of Dairy Products on Bioavailability of Zinc from Other Food Products: A Review of Complementarity at a Meal Level.
In this paper, we reviewed the role of dairy products in dietary zinc absorption. Dairy products can have a reasonable contribution for dietary zinc intake in Western diets, where dairy consumption is high. However, the co-ingestion of dairy products can also improve zinc absorption from other food products. Such improvements have been observed when dairy products (e.g., milk or yoghurt) were ingested together with food such as rice, tortillas or bread products, all of which are considered to be high-phytate foods with low inherent zinc absorption. For foods low in phytate, the co-ingestion of dairy products did not improve zinc absorption. Improved zinc absorption of zinc from high-phytate foods following co-ingestion with dairy products may be related to the beneficial effects of the citrate and phosphopeptides present in dairy products. Considering that the main dietary zinc sources in areas in the world where zinc deficiency is most prevalent are typically high in phytate, the inclusion of dairy products in meals may be a viable dietary strategy to improve zinc absorption.


Cavitary lung lesions caused by Pneumocystis jirovecii in setting of common variable immune deficiency.
Pneumocystis pneumonia affects immunocompromised hosts. The typical imaging finding is bilateral diffuse ground glass opacities. Here we presented a case of Pneumocystis causing biopsy-confirmed cavitary lung lesions in a patient with a predominant B cell defect with common variable immune deficiency.


Correction: Ambient and household PM2.5 pollution and adverse perinatal outcomes: A meta-regression and analysis of attributable global burden for 204 countries and territories.
[This corrects the article DOI: 10.1371/journal.pmed.1003718.].


Metabolic capabilities are highly conserved among human nasal-associated Corynebacterium species in pangenomic analyses.
Corynebacterium species are globally ubiquitous in human nasal microbiota across the lifespan. Moreover, nasal microbiota profiles typified by higher relative abundances of Corynebacterium are often positively associated with health. Among the most common human nasal Corynebacterium species are C. propinquum, C. pseudodiphtheriticum, C. accolens, and C. tuberculostearicum. Based on the prevalence of these species, at least two likely coexist in the nasal microbiota of 82% of adults. To gain insight into the functions of these four species, we identified genomic, phylogenomic, and pangenomic properties and estimated the functional protein repertoire and metabolic capabilities of 87 distinct human nasal Corynebacterium strain genomes: 31 from Botswana and 56 from the U.S. C. pseudodiphtheriticum had geographically distinct clades consistent with localized strain circulation, whereas some strains from the other species had wide geographic distribution across Africa and North America. All four species had similar genomic and pangenomic structures. Gene clusters assigned to all COG metabolic categories were overrepresented in the persistent (core) compared to the accessory genome of each species indicating limited strain-level variability in metabolic capacity. Moreover, core metabolic capabilities were highly conserved among the four species indicating limited species-level metabolic variation. Strikingly, strains in the U.S. clade of C. pseudodiphtheriticum lacked genes for assimilatory sulfate reduction present in the Botswanan clade and in the other studied species, indicating a recent, geographically related loss of assimilatory sulfate reduction. Overall, the minimal species and strain variability in metabolic capacity implies coexisting strains might have limited ability to occupy distinct metabolic niches.


α-D-Glucosidase inhibitory activity of polysaccharide isolated from Acacia tortilis gum exudate.
The study aims to explore the antihyperglycemic activity of Acacia tortilis polysaccharide isolated from the gum exudate. α-d-Glucosidase from Saccharomyces cerevisiae and rat small intestine was used as in vitro model to assess α-d-glucosidase inhibitory activity of the polysaccharide against yeast and mammalian enzyme. The reduction in postprandial blood glucose level after carbohydrate rich diet fed to Albino Wistar rats was employed as in vivo model of α-d-glucosidase inhibition. The study revealed α-d-glucosidase inhibitory activity of the polysaccharide in both in vitro as well as in vivo models. Therefore, polysaccharide isolated from A. tortilis plant gum exudate may be a potential drug for diabetes mellitus and its complications.


[Studies on transplanting suspension-cultured protocorms of Dendrobium candidum onto solid culture medium].
The suspension-cultured protocorms of Dendrobium candidum were transplanted on the solid culture medium for studying the factors influencing their differentiation and growth. The growth and differentiation of protocorms were detected when different base-media, plant phytohormones, carbohydrates and pH were applied. The diluted MS medium promotes the growth of protocorms but inhibit differentiation. The phytohormone NAA, IAA, IBA and GA are helpful to the growth and differentiation of protocorms, however, the low pH values and presence of autoclaved fungi have suppressive effects on protocorms. The fungi also induce morphological variation of protocorms.


A multiple-baseline evaluation of the treatment of subjective tinnitus with relaxation training and biofeedback.
Six subjects with subjective tinnitus received training in relaxation techniques and EMG and thermal biofeedback in a multiple-baseline across-subjects design. Daily tinnitus disturbance and sleep disturbance diaries were kept throughout. Audiological and psychological evaluations were made at various treatment phases. At posttreatment assessment, subjects also completed global ratings of their perceived improvement in ability to cope with the tinnitus, stress caused by the tinnitus, and severity of the tinnitus, as well as their overall satisfaction with the treatment. Ratings on the global scales were generally very positive. By way of contrast, the daily diary results revealed little if any treatment effect. The implications of these disparate results are discussed.


Designing of peptide substrates. Different approaches exemplified by new chromogenic substrates for kallikreins and urokinase.
Chromogenic peptide substrates for serine proteases have been designed by using two approaches: (1) by using the natural substrate as a model and (2) by structure-activity correlations obtained through screening of a large number of tripeptides. Some recent examples, substrates for kallikreins and urokinase are given.


Structural factors in the odor of alpha-santalol derivatives.
Alpha-Santalol is a sesquiterpene that is a major constituent of sandalwood (Santalum album L.), and is responsible for its distinctive woody odor. We replaced the polycyclic moiety and hydroxyl group of alpha-santalol with other moieties, and we compared the odors of the E/Z-isomers and their saturated analogues. Our previous study of the structure-odor relationships of alpha-santalols bearing hydroxyl, formyl, formyloxy, and acetoxy functional groups showed there was a similarity in odor between the Z-isomer and its saturated analogue. We synthesized alpha-santalols with a benzyl group in place of the hydroxyl group, because many benzyl compounds have strong characteristic odors. We found similar odors for the E-isomer and its saturated analogue. In contrast, the odors of the alpha-santalol derivatives with a hydroxyl, formyl, formyloxy, or acetoxy group were different. We also replaced the bulky polycyclic moiety with a linear alkyl chain. The polycyclic moiety was the most important structural factor in the characteristic sandalwood odor. The synthesis of derivatives and the evaluation of their odor allowed us to identify the key structural factors in the odor of alpha-santalol.


Review of underactive bladder.
In clinical practice, many patients cannot empty their bladders within an acceptable duration. Common complaints include weak urinary stream and incomplete emptying, which may affect quality of life. Bladder emptying requires sufficient detrusor contractile power, velocity, and durability. The urodynamic term for inadequate detrusor contraction is detrusor underactivity (DU). Although this definition was provided by the ICS, it may not be clinically practical. Analogous to the relationship between overactive bladder (OAB) and detrusor overactivity (DO), the symptom complex caused by DU is termed underactive bladder (UAB). Many conditions lead to UAB, such as advanced age, neurogenic bladder and BOO, but the definite pathophysiology directly leading to UAB is still being widely studied without a widely-accepted consensus. The preferred mainstream treatment for increased residual urine volume caused by UAB is intermittent catheterization, while pharmacotherapy is still disappointing after decades of development. There are no studies on surgical treatment for UAB with an acceptable level of evidence. We reviewed the recent literature on UAB and DU to provide a comprehensive discussion of the related presentation, etiology, diagnosis and management.


A Comparative Study of a Small Series of Patients (50 Patients) with Pelvic Varicose Veins Treated with Plugs Alone or Plugs and Polidocanol.
Level 2. To compare the safety and efficacy of vascular plug (VP) and vascular plug and polidocanol foam (VPPF) treatments for embolization in pelvic congestion syndrome (PCS). A comparative, prospective, two-center study enrolled 50 women with PCS from January 2019 to January 2020. The patients were divided into two groups, and embolization was performed with VP (n = 25) and VPPF (n = 25) treatments. The mean age of the patients was 45.6 years ± 6.9. Three clinical parameters were assessed: abdominal pain, dyspareunia, and lower limb pain. The primary outcome (clinical success at 1 yr using a VAS), number of devices, procedure and fluoroscopy times, radiation doses, costs, and complications were compared. The participants were followed-up at 1, 3, 6, and 12 months. At the 1-year follow-up, clinical success did not significantly differ between the two groups (VP vs. VPPF) regarding the improvement of the symptoms analyzed (pelvic pain, dyspareunia, lower extremity pain, and other symptoms (p < 0.05)). The mean number of devices per case was 4 ± 1.1 for the VP group and 2 ± 0.31 for the VPPF group (p < 0.001). No major complications were recorded in either group. The VPPF group had a significantly longer fluoroscopy time (42.8 min ± 14.2 vs. 25.4 min ± 7) and longer radiation dose (VPPF air kerma 839.4 ± 513 vs. VP air kerma 658.4 mGy ± 355 (all p < 0.001)). Embolization for PCS resulted in pain relief in 90% of patients; the use of polidocanol did not demonstrate changes in the clinical outcome. The use of a VP alone was associated with decreased fluoroscopy time and radiation dose.


Reducing surgical site infections following total hip and knee arthroplasty: an Israeli experience.
To assess the changes observed in surgical site infection (SSI) rates following total joint arthroplasty (TJA) after the introduction of an infection control programme and evaluate the risk factors for the development of these infections. Prospective cohort study. Large tertiary medical centre in Israel. Data about SSIs and potential prophylaxis-, patient-, and procedure-related risk factors were collected for all patients who underwent elective total hip and total knee arthroplasty during the study period. Multivariant analyses were conducted to determine which significant covariates affected the outcome. During the 76-month study period, SSIs (superficial and deep) occurred in 64 (4.4%) of 1554 patients. As compared with the 34 (7.7%) SSIs that occurred in the first 25 months, there were 23 (4.7%) SSIs in the following 25 months, and only 7 (1.3%) SSIs in the last third of the study (p = 0.058 and <0.001, respectively). A multiple logistic regression model indicated that risk factors for prosthetic joint infection were a National Nosocomial Infections Surveillance (NNIS) System surgical patient risk index score of 1 (OR 1.8; 95% CI 1.1-3.1) or 2 (OR 2.8; 95% CI 1.2-11.8). The incidence of SSI was not correlated with the timing, nor the duration of antibiotic prophylaxis. The introduction of preventive measures and surveillance coincided with a significant reduction in SSIs following TJA in our institution. The risk of infection correlated with higher scores in the NNIS System surgical patient risk.


Monozygotic twins with trisomy 21 and partial agenesis of the corpus callosum.
Trisomy 21 is the most common viable trisomy. Although it is invariably associated with mild to severe developmental delay and intellectual disability, no gross central nervous system malformation has been consistently identified in individuals with trisomy 21. We present the case of a monozygotic twin pregnancy in which both fetuses were identified as having trisomy 21 and partial agenesis of the corpus callosum. We discuss this rare association in the context of an emerging understanding of the neurobiology of trisomy 21.


Increased aortic stiffness can predict perioperative cardiovascular outcomes in patients undergoing noncardiac, nonvascular surgery.
Aortic stiffness is an early marker of arteriosclerosis and associated with cardiovascular mortality. However, the impact of aortic stiffness on perioperative cardiovascular outcomes in patients undergoing noncardiac surgery is unknown. The study population was composed of 660 consecutive adults aged 18 years and over (mean age = 65.3 ± 14 years) who underwent intermediate-risk (nonvascular), noncardiac surgery between January 2010 and February 2011. Nonemergency, non-day-case, open surgical procedures were enrolled. Aortic stiffness indices were calculated from the aortic diameters measured by echocardiography. Electrocardiography and cardiac biomarkers were evaluated 1 day before surgery, and on days 1, 3, and 7 after surgery. Eighty patients (12.1%) experienced perioperative cardiovascular events (PCE). Preoperative aortic distensibility (AD) (2 ± 1.3 vs. 2.9 ± 1.1 cm2/dyn/10(3), P < 0.001) and aortic strain (AS) (4.4 ± 2.4 vs. 6.4 ± 1.9, P < 0.001) of the patients with PCE were significantly lower than in patients without PCE. Univariate analysis showed a significant association between age, diabetes mellitus (DM), coronary artery disease, preoperative atrial fibrillation, American Society of Anesthesiologists (ASA) status, Revised Cardiac Risk Index, left ventricle ejection fraction (LVEF), AD, aortic strain, and in-hospital PCE. However, on multivariate logistic regression analysis, only AD (OR: 1.94, 95% CI: 1.1-3.4; P = 0.02), AS (OR: 0.45, 95% CI: 0.3-0.6; P < 0.001), DM (OR: 2.28, 95% CI: 1.08-4.82; P = 0.03), and LVEF (OR: 0.96, 95% CI: 0.93-0.99; P = 0.03) remained as significant variables associated with PCE. Impaired elastic properties of the aorta are associated with increased PCE rates in patients undergoing noncardiac, nonvascular surgery.


Exercise-associated hyponatraemia: a mathematical review.
In 1958, Edelman and colleagues empirically showed plasma sodium concentration ([Na+]p) to be primarily a function of the sum of exchangeable sodium and potassium (E) divided by total body water (TBW). Based on Edelman's equation, Nguyen and Kurtz derived an equation to show how [Na+]p changes as a function of TBW, change in TBW (DeltaTBW), and change in the sum of exchangeable sodium and potassium (DeltaE). Using the Nguyen-Kurtz equation, the present study examines the sensitivity of [Na+]p to these parameters: [Na+]p is very sensitive to DeltaTBW and moderately sensitive to DeltaE, and is modulated by TBW. For example, for a person with 50 L TBW, a net increase of 1L water lowers [Na+]p by 3.2 mEq/L, but for a person with 25 L TBW it lowers [Na+]p by 6.3 mEq/L (assuming initial [Na+]p is 140 mEq/L). In each case, a loss of 159 mEq of sodium plus potassium (roughly equivalent to 1.5 teaspoons of table salt) would be required to produce the same effect as the net increase of 1 L water. The present review demonstrates why fluid overload predominates over electrolyte loss in the aetiology of exercise-associated hyponatraemia (EAH), and why the excretion of electrolyte-dilute urine is highly effective in correcting EAH (nonetheless, loss of sodium and potassium is significant in long events in warm weather). Sports drinks will, if overconsumed, result in hyponatraemia. Administration of a sports drink to an athlete with fluid overload hyponatraemia further lowers [Na+]p and increases fluid overload. Administration of either a sports drink or normal (0.9%) saline increases fluid overload.