Completing accreditation during the COVID-19 pandemic: A step-by-step process for success.
Many higher-education administrative processes have transitioned to the online environment due to the COVID-19 pandemic. Nursing program accreditation site visits were not spared from this shift. This article describes the step-by-step online, interactive, and collaborative process one nursing department used for program re-accreditation. Kotter's 8-step process for accelerating change informed this work. Positive outcomes included increased faculty engagement and knowledge in the accreditation process and an ongoing accreditation readiness team. Recommendations include forming an accreditation committee, appointing program champions, utilizing a learning management system and a cloud-based storage system, and celebrating successes. This process could be replicated by other nursing programs undergoing accreditation.


Molecular identification of a rare hemoglobin variant, Hb J-Iran [beta77(EF1)His->Asp], in Denizli province of Turkey.
Hb J-Iran [beta77(EF1)His-Asp], a rare hemoglobin variant that does not present health problems, was reported for the first time in the Turkish population in 1986. Our case is the fourth case reported in Turkey and the first case from the Denizli province.


Patients with pulmonary tuberculosis develop a strong humoral response against methylated heparin-binding hemagglutinin.
Reactivities of human sera against selected recombinant Mycobacterium tuberculosis antigens were assessed by enzyme-linked immunosorbent assay. The results obtained indicate that patients with tuberculosis (TB) do not develop a strong humoral response against PE_PGRS and PPE proteins or against the Ag85B and heparin-binding hemagglutinin (HBHA) recombinant antigens. Conversely, purified methylated HBHA was strongly recognized by sera obtained from TB patients compared to controls.


Analysis of Four-Dimensional Data for Total Body PET Imaging.
The high sensitivity and total-body coverage of total-body PET scanners will be valuable for a number of clinical and research applications outlined in this article.


Evolution of cardiac changes in young insulin-dependent (type 1) diabetic patients--one more piece of the puzzle of diabetic cardiopathy.
Based on our recent reports that increased myocardial contractility has been found in newly diagnosed diabetic patients, and that diastolic (D) dysfunction precedes systolic (S) dysfunction, we suggested that the development of diabetic cardiopathy passes through the following stages: (I) increased myocardial contractility, (II) intact S and D function, (III) intact S function and D dysfunction, and (IV) S and D dysfunction. The aim of this pilot study was to test this hypothesis. One hundred fifty-seven young (26.2 +/- 7.4 years) cardiac-asymptomatic patients with type I diabetes and 54 healthy subjects were studied using M-mode echocardiography. The presence of at least one of the variables for systolic function (ejection fraction, mean velocity of circumference, fiber shortening, and stroke index) or diastolic function [left atrium emptying index (LAEI), EFo slope of anterior mitral leaflet, and isovolumetric relaxation time (IRT)] outside the control mean +/- 2 SD was interpreted as an increased or depressed myocardial contractility, and diastolic dysfunction, respectively. The severity of diabetic complications (retinopathy, nephropathy, and cardiac autonomic neuropathy) was evaluated by the diabetic complication index (DCI = 0 divided by 6 scores). Our hypothesis was confirmed significantly (p < 0.001) in 148 (94%) patients with diabetes. Duration of diabetes and DCI progressed significantly (ANOVA: F = 36.6, p < 0.001; F = 70.8, p < 0.001) with hypothetical stages. Diastolic dysfunction was more pronounced in stage IV than in stage III: IRT (80.5 +/- 18.6 ms vs. 62.5 +/- 16.4, p < 0.001), EFo (63 +/- 15 mm/s vs. 72 +/- 21, p < 0.05), LAEI (0.58 +/- 0.13 vs. 0.8 +/- 0.15, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Structural and thermodynamic analyses of solute-binding Protein from Bifidobacterium longum specific for core 1 disaccharide and lacto-N-biose I.
Recently, a gene cluster involving a phosphorylase specific for lacto-N-biose I (LNB; Galbeta1-3GlcNAc) and galacto-N-biose (GNB; Galbeta1-3GalNAc) has been found in Bifidobacterium longum. We showed that the solute-binding protein of a putative ATP-binding cassette-type transporter encoded in the cluster crystallizes only in the presence of LNB or GNB, and therefore we named it GNB/LNB-binding protein (GL-BP). Isothermal titration calorimetry measurements revealed that GL-BP specifically binds LNB and GNB with K(d) values of 0.087 and 0.010 microm, respectively, and the binding process is enthalpy-driven. The crystal structures of GL-BP complexed with LNB, GNB, and lacto-N-tetraose (Galbeta1-3GlcNAcbeta1-3Galbeta1-4Glc) were determined. The interactions between GL-BP and the disaccharide ligands mainly occurred through water-mediated hydrogen bonds. In comparison with the LNB complex, one additional hydrogen bond was found in the GNB complex. These structural characteristics of ligand binding are in agreement with the thermodynamic properties. The overall structure of GL-BP was similar to that of maltose-binding protein; however, the mode of ligand binding and the thermodynamic properties of these proteins were significantly different.


Dynamics of intracellular calcium in cultured human keratinocytes after localized cell damage.
Recovery of cultured keratinocytes after scratch damage is considered to be a wound-healing model. In this study, we observed changes in intracellular calcium concentration ([Ca(2+) ]i ) in cultured human keratinocytes after scratch damage. Immediately after scratch damage, a wave of increased [Ca(2+) ]i radiated outward from the damaged area and then disappeared gradually. But, [Ca(2+) ]i remained elevated in a peripheral layer of cells around the damaged area for several minutes. This layer did not appear in calcium-free medium. When the culture was switched to calcium-free medium for 30 min immediately after scratch damage, then switched back to standard (Ca(2+) -containing) medium, the recovery ratio after 24 h was approximately 25% lower than that of the culture in standard medium throughout. We speculate that delineation of damage sites by a layer of cells with increased [Ca(2+) ]i might be part of a signalling pathway that appropriately directs the wound-healing process in epidermis.


Microglia sense and suppress epileptic neuronal hyperexcitability.
Microglia are the resident immune cells of the central nervous system, undertaking surveillance role and reacting to brain homeostasis and neurological diseases. Recent studies indicate that microglia modulate epilepsy-induced neuronal activities, however, the mechanisms underlying microglia-neuron communication in epilepsy are still unclear. Here we report that epileptic neuronal hyperexcitability activates microglia and drives microglial ATP/ADP hydrolyzing ectoenzyme CD39 (encoded by Entpd1) expression via recruiting the cAMP responsive element binding protein (CREB)-regulated transcription coactivator-1 (CRTC1) from cytoplasm to the nucleus and binding to CREB. Activated microglia in turn suppress epileptic neuronal hyperexcitability in a CD39 dependent manner. Disrupting microglial CREB/CRTC1 signaling, however, decreases CD39 expression and diminishes the inhibitory effect of microglia on epileptic neuronal hyperexcitability. Overall, our findings reveal CD39-dependent control of epileptic neuronal hyperexcitability by microglia is through an excitation-transcription coupling mechanism.


Autobiographical memory loss following a right prefrontal lobe tumour resection: a case report and review of the literature.
The right prefrontal lobe has not traditionally been considered eloquent brain. Resection of tumours within this region does not typically lead to permanent functional impairment. In this report, we highlight the case of a patient who developed autobiographical memory loss following an uncomplicated resection of a right prefrontal tumour. A previously fit and well 15-year old presented with a persistent right-sided headache. An MRI demonstrated an expanded right mid-frontal gyrus with changes consistent with a low-grade tumour. The patient underwent a right-sided craniotomy and resection of the lesion which was confirmed as a WHO grade II diffuse astrocytoma. Postoperatively, the patient reported profound retrograde amnesia for a range of memory components, in particular autobiographical memory and semantic memory. Postoperative imaging showed a good resection margin with no evidence of underlying brain injury. Over an 18-month period, the patient showed no improvement in autobiographical memory; however, significant relearning of semantic knowledge took place and her academic performance was found to be in line with expectations for her age. In this report, we discuss a case and review the literature on the role of the right prefrontal cortex in memory and caution on the perception of right prefrontal non-eloquence.


Spasticity and spastic dystonia: the two faces of velocity-dependent hypertonia.
Spasticity and spastic dystonia are two separate phenomena of the upper motor neuron syndrome. Spasticity is clinically defined by velocity-dependent hypertonia and tendon jerk hyperreflexia due to the hyper-excitability of the stretch reflex. Spastic dystonia is the inability to relax a muscle leading to a spontaneous tonic contraction. Both spasticity and spastic dystonia are present in patients who are at rest; however, only patients with spasticity are actually able to kept their muscles relaxed prior to muscle stretch. The idea that has inspired the present work is that also in patients with spastic dystonia the stretch reflex is likely to be hyper-excitable. Therefore, velocity-dependent hypertonia could be mediated not only by spasticity, but also by spastic dystonia. Tonic stretch reflexes in the rectus femoris muscle were evoked in 30 patients with multiple sclerosis showing velocity-dependent hypertonia of leg extensors and the habituation of the reflex was studied. Moreover, the capability of relax the muscle prior to muscle stretch (spastic dystonia) was also investigated. A tonic stretch reflex was evoked in all the enrolled patients. 73% of the patients were able to relax their rectus femoris muscle prior to stretch (spasticity). In the overwhelming majority of these patients, the tonic stretch reflex decreased during repeated stretches. In the remaining 27% of the subjects, the muscle was tonically activated prior to muscle stretch (spastic dystonia). In the patients in whom spastic dystonia progressively increased over the subsequent stretches (50% of the subjects with spastic dystonia), the habituation of the reflex was replaced by a progressive reflex facilitation. This study shows for the first time that velocity-dependent hypertonia can be caused by two distinct phenomena: spasticity and spastic dystonia. The habituation of the tonic stretch reflex, which is a typical feature of spasticity, is replaced by a reflex facilitation in the half of the subject with spastic dystonia. These preliminary findings suggest that differentiating the two types of velocity-dependent muscle hypertonia (spasticity and spastic dystonia) could be clinically relevant.


Rabbi Yaacov Wazana: a Jewish healer in the Atlas Mountains.
Rabbi Yaacov Wazana, a Jewish healer who died more than 30 years ago in the Atlas Mountains, was a "deviant" type within the Jewish Moroccan curing system. Despite his deviant features, or rather because of them, his memory still vividly reverberates among former members of his community living today in Israel. In seeking to construe a meaningful reading of Wazana's life-story, this work takes into account the fact that he is a mediated object of study whose life can only be examined through historically situated texts. Wazana's script is interpreted on two levels. First, an attempt is made to illuminate the possible motivational structures that fuelled his inexhaustible therapeutic energies and shaped his unique life-style. Dwelling on Wazana's special relations with his parents (and their internalized representations), this psychological interpretation should be evaluated with caution as it cuts across two levels of mediation and may reflect on the informants' or the researcher's psychology imposed on Wazana. Second, a symbolic reading of Wazana's calling is suggested centering on his marginality and unique location at the edge of the social order. Being at once human and demon-bound, Jew and Muslim, old and young, holy and impure, he dissolved the boundaries of the major contrasting social categories of his culture and integrated them. This bridging function may have nurtured his image as an omnipotent healer.


Measurement of nitric oxide spectral parameters: Considering the effects of CO2 and H2O.
A continuous-wave quantum cascade laser (CW-QCL) based spectrometer is developed to investigate the high-resolution spectral parameters of nitric oxide (NO). Line strengths and nitrogen (N2)-, carbon dioxide (CO2)-, water vapor (H2O)-, broadening coefficients for NO R(6.5) are measured. The spectral region ranging from 1989 cm-1 to 1901 cm-1, which is suitable for the in situ laser sensing of trace NO, is investigated. Spectral parameters are determined by fitting absorption spectra with multi-peak Voigt profiles. The measured intensities are compared to the HITRAN2020 database to assess the performance of the system and a good agreement within ±5% is obtained for the established lines. The measurement results are useful for the design of a spectroscopic sensor for monitoring exhaled breath NO, vehicle exhaust, and industrial emissions.


Percutaneous screw and axial Kirschner wire fixation for acute transscaphoid perilunate fracture dislocation.
In this retrospective, nonrandomized study, we evaluated the clinical outcomes of percutaneous screw and K-wire fixation in the treatment of acute transscaphoid perilunate fracture dislocation. Between 2004 and 2009, we studied 24 patients treated by fixation with a 2.0-mm (0.078-in) axial K-wire across the capitolunate joint and a percutaneous screw (3.0-mm AO cannulated screws were used in 13 patients, and Herbert-Whipple screws were used in 11 patients) within 7 days of the injury. We performed a comparative radiographic assessment of the scapholunate angle, radiolunate angle, capitolunate angle, revised carpal height ratio, and gap between the scapholunate joint between the injured wrist and the contralateral, healthy wrist. Clinical outcomes were evaluated on the basis of range of motion, pain, functional status, and Mayo scores. Twenty-three patients (96%) achieved scaphoid union at a mean union time of 18 weeks (range, 14-28 wk). Radiographic assessments revealed no statistically significant difference between the injured wrist and the contralateral, healthy wrist. However, significant differences were noted in the mean range of motion during flexion and forearm supination between the injured wrist and contralateral healthy wrist. The mean wrist function results were encouraging, and the average Mayo score was 83. A percutaneous procedure involving screw fixation for the scaphoid fracture and an axial K-wire fixation for intercarpal dislocation is a successful treatment for acute transscaphoid perilunate fracture dislocation. Prognostic III.


Copeptin as a novel biomarker in nocturnal enuresis.
To investigate the relation between copeptin, arginine vasopressin (AVP), and nocturnal enuresis (NE). Forty-four patients with NE and 44 healthy children aged between 6 and 14 years were enrolled. Patients with nonmonosymptomatic and secondary NE were excluded from the study. A small questionnaire, filled by parents, collected information about sociodemographic characteristics. Blood was obtained for plasma AVP and copeptin concentrations. Copeptin levels were significantly lower in patient group (3.74 ± 1.44 pg/mL) than the control group (16.57 ± 3.91 pg/mL), whereas AVP levels were not significantly different between groups. Copeptin levels were significantly lower in patients (3.17 ± 1.15 pg/mL) who had bed-wetting 2 or more nights a week, which is considered as severe bed-wetting, than the patients (4.95 ± 1.24 pg/mL) who had bed-wetting 1 night or less than 1 night a week. This study demonstrates the presence of decreased levels of copeptin in patients with NE compared with healthy patients. AVP levels were not different between groups. To our knowledge, this is the first report assessing the relationship between copeptin and NE.


Observations on the binding of adenosine 3':5'-monophosphate to cell membrane fragments from ox cerebral cortex.
Microsomal or synaptosome membrane fragments from ox brain bind cyclic AMP with a pH optimum of 7.0. Scatchard analysis shows the presence of at least two binding sites. Cyclic GMP and cyclic IMP only inhibit binding at concentrations 5000 times that of cyclic AMP and even higher concentration ratios of ATP and AMP have no effect. Membrane fragments saturated with cyclic [3-H]AMP lost less than 7% of bound nucleotide on incubation at 0 degrees C for 45 min but lost 25 % in the same period in the presence of 10 muM non-radioactive cyclic AMP.


Distribution of free D-serine in vertebrate brains.
Free D-serine distribution in vertebrate brains was investigated. In various brain regions of the lower vertebrate species, carp, frog and chick, free D-serine levels were low. On the contrary, in the mammals, mouse, rat and bull, the contents of free D-serine were high in the forebrain (around 400 nmol/g wet weight, and the ratio of D-serine to L-serine, was D/L = 0.4), and low in the hindbrain. In developing mice, D-serine levels in the cerebrum increased with age and attained the adult level (D/L = 0.40) 8 weeks after birth. In the cerebellum and brain stem, the free D-serine levels increased with age until 2 weeks, followed by a decrease to the adult levels: the D/L ratios remained constant until 2 weeks of age, then decreased to 0.03 in the cerebellum and 0.12 in the brain stem. Free D-serine was shown not to be of microbial origin using germ-free mice. In the rat forebrain, D-serine was evenly distributed in two cerebral regions, namely frontal and occipital lobes. The D/L ratios in other regions of forebrain, hippocampus and hypothalamus, were comparable to the cerebrum (D/L = 0.4), while that in the olfactory bulb was lower (D/L = 0.12). In the rat cerebrum, the D-serine content in the grey matter was significantly higher than that in the white matter. The contents of free D-serine in bovine cerebrum and cerebellum were similar to those in other mammalian brains, but the D/L ratio for bovine cerebral grey matter was lower than that for the cerebral white matter.(ABSTRACT TRUNCATED AT 250 WORDS)


Intermittent point prevalence surveys on healthcare-associated infections, 2011 and 2016, in England: what are the surveillance and intervention priorities?
Point prevalence surveys are an important surveillance method for determining the burden of healthcare-associated infections (HCAIs). To outline the key results of two point prevalence surveys in England (2011 and 2016). All National Health Service and independent sector hospitals in England were eligible to participate. Data were collected between September and November in both 2011 and 2016 based on the protocol and codebook devised by the European Centre for Disease Prevention and Control. Analysis was performed using Stata Version 13 and SAS Version 9.3. A mixed-effects model was applied, which allowed estimation of organization-specific means and accounted for the heterogeneity in the responses from different organizations. A total of 100,755 case records were included (52,433 in 2011 and 48,312 in 2016). The estimated prevalence of HCAIs was slightly higher in 2016 [6.89%, 95% confidence interval (CI) 6.21-7.57%] than in 2011 (6.41%, 95% CI 5.75-7.06%). In both surveys, the prevalence of HCAIs was highest in adult intensive care units (23.1% in 2011, 21.2% in 2016), and pneumonia/lower respiratory tract infections was the most common cause of HCAIs (22.7% in 2011 vs 29.2% in 2016). Inpatients in acute hospitals were older and had higher risk of dying in 2016 compared with 2011; however, the proportion of inpatients with HCAIs or on antibiotics did not differ significantly. The burden of HCAIs in English hospitals increased slightly between 2011 and 2016. However, the proportion of inpatients with HCAIs or on antibiotics did not differ significantly.


The effect of vaccination with the lysate of heat-shocked tumor cells on nitric oxide production in BALB/c mice with fibrosarcoma tumor.
The aim of this study was to investigate the effect of heat shock protein-70 (HSP-70) on splenocyte proliferation and nitric oxide (NO) production in the BALB/c mice fibrosarcoma tumor model. To do so, HSP-70 was induced in the lysate of heat-shocked tumor cells and WEHI-164 cells (mouse fibrosarcoma cell line) were injected subcutaneously into the right flank of inbred BALB/c mice to establish a tumor model. Three animal bearing tumor groups were applied: the test group; vaccinated with HSP-70 enriched tumor lysate; control group I, vaccinated with tumor lysate only; and control group II, which received PBS. Using immunoblot analysis, an increase of HSP-70 expression was detected in the lysate of heat-shocked cells in comparison with non-heat-shocked cells. The effect of the test lysate on NO production was measured both in vitro and in vivo in the peritoneal macrophages and splenocytes of tumor bearing mice, respectively. The result showed a significant increase in NO production both in vitro by peritoneal macrophages and in vivo after immunization with HSP-70 enriched tumor lysate. In addition, tumor growth was significantly postponed and the proliferation of splenocytes was increased in the test group. Our results indicate that the lysate of heat-shocked tumor cells was more potent than that of non-heat-shocked tumor cells in inducing anti-tumor immunity. Since production of NO by HSP-activated antigen presenting cells (APCs) is likely to affect innate immunity and tumor growth, the probable mechanism of postponing tumor growth would be NO production by innate immune cells. These findings provide a useful therapeutic model for developing novel approaches to cancer treatments.


Source identification of soil elements and risk assessment of trace elements under different land uses on the Loess Plateau, China.
To investigate the source identification of soil elements and risk assessment of trace elements under different land-use types, 32 pairs of topsoil samples (0-20 cm) were collected from two subcatchments in the Liudaogou watershed. The areas of the two subcatchments were 0.343 and 0.045 km2, respectively, and the two subcatchments were divided into four land-use types, including bare land, forestland (FL), grassland (GL) and check-dam land (CDL). The results showed that the coefficients of variations of all soil elements indicated moderate spatial variation. The mean concentrations of Cu, K, Mn, Na and Zn under different land-use types exceeded the soil background values. The results of correlation analysis and principal component analysis illustrated that high homology existed between Cu and Mn in subcatchment 1, and the main source was from coal mines and smelters. Consistent sources of Zn and K in subcatchment 1 were mainly fertilizers and sewage sludge. Cu, K, Mg, Mn, Na and Zn in subcatchment 2 had similar sources, mainly mining and smelting plants, fertilizers and sewage. In addition, Ca had high homology with Fe in two subcatchments, mainly from natural weathering. The enrichment factor values indicated that there was a certain degree of trace element pollution. The values of the pollution index and Nemerow integrated pollution index revealed that moderate pollution was mainly concentrated in FL, GL and CDL. The trace element pollution of GL and CDL may induce contamination of the food chain and threaten human health safety.


Incidental carcinoma of the prostate at the time of transurethral resection: importance of evaluating every chip.
Incidental adenocarcinoma of the prostate has been divided into stage A1--less than 3 foci of well differentiated adenocarcinoma present and stage A2--3 or more foci of poorly differentiated tumor present. The clinical significance of these 2 stages has been well documented, with stage A1 lesions causing no increased mortality, while up to 30 per cent of patients with clinical stage A2 disease will have positive pelvic lymph nodes at exploration and, thus, will have surgical stage D1 tumor. Most pathology laboratories submit only a fraction of the transurethral resection chips for permanent blocks. In an effort to evaluate the over-all incidence and distribution of stages A1 and A2 lesions were began a prospective study in 1978 whereby all prostatic chips were submitted for permanent sections. A review of 500 consecutive cases of transurethral resection for clinically benign prostates before 1978 revealed 43 cases of adenocarcinoma: 10 (23 per cent) stage A1 and 33 (77 per cent) stage A2. A review of a similar series of 500 consecutive patients since 1978 revealed 71 cases of adenocarcinoma: 17 (24 per cent) clinical stage A1 and 54 (76 per cent) clinical stage A2. Thus, we found that since 178 incidental adenocarcinoma of the prostate has increased by 65 per cent and the distribution of stages A1 and A2 lesions has remained unchanged, 76 per cent of these lesions being clinical stage A2 with its much greater clinical significance. Evaluation of every chip does make a clinically significant difference in the subsequent management of patients with incidental adenocarcinoma of the prostate.


OLAV-PMF: a novel scoring scheme for high-throughput peptide mass fingerprinting.
We propose a new type of probabilistic scoring scheme framework for protein identification from peptide masses. We first introduce the framework itself and explain its requirements. In a second part, we describe a particular implementation and test it on a data set of more than 8000 MALDI-TOF spectra with known contents. Doing so, we also compare its performance to two widely used scoring schemes, thereby demonstrating the potential of the proposed approach.


Establishing normative data for the evaluation of cognitive performance in Huntington's disease considering the impact of gender, age, language, and education.
A declining cognitive performance is a hallmark of Huntington's disease (HD). The neuropsychological battery of the Unified HD Rating Scale (UHDRS'99) is commonly used for assessing cognition. However, there is a need to identify and minimize the impact of confounding factors, such as language, gender, age, and education level on cognitive decline. Aim is to provide appropriate, normative data to allow clinicians to identify disease-associated cognitive decline in diverse HD populations by compensating for the impact of confounding factors METHODS: Sample data, N = 3267 (60.5% females; mean age of 46.9 years (SD = 14.61, range 18-86) of healthy controls were used to create a normative dataset. For each neuropsychological test, a Bayesian generalized additive model with age, education, gender, and language as predictors was constructed to appropriately stratify the normative dataset. With advancing age, there was a non-linear decline in cognitive performance. In addition, performance was dependent on educational levels and language in all tests. Gender had a more limited impact. Standardized scores have been calculated to ease the interpretation of an individual's test outcome. A web-based online tool has been created to provide free access to normative data. For defined neuropsychological tests, the impact of gender, age, education, and language as factors confounding disease-associated cognitive decline can be minimized at the level of a single patient examination.


Combined osmotic dehydration and drying process of pirarucu (Arapaima gigas) fillets.
The osmotic dehydration (OD) and complementary drying of pirarucu (Arapaima gigas) fillets were studied. Pieces of the dorsal portion of pirarucu (60 mm × 20 mm × 10 mm) underwent OD in a binary solution (NaCl-water) with the application of vacuum pulse following a central rotatable composite design. The effect of the following process variables was assessed: temperature (20-40 °C), osmotic solution concentration (15-25% NaCl), and vacuum pulse pressure (7-101 kPa) on water loss (WL), solid gain (SG), and water activity (aw). OD kinetics was obtained and the Peleg model was fitted to WL and SG data. The osmotically dehydrated pirarucu was dried (40-70 °C) in a fixed-bed dryer and mathematical models were fitted to the drying data. The optimal operational condition for the OD process was 35 °C, solution with 25% NaCl, and atmospheric pressure, which yielded WL of 14.87 ± 1.46%, SG of 8.56 ± 0.45%, and aw of 0.87 ± 0.02. The Peleg model efficiently predicted the WL and SG kinetics. The increase in the water loss in drying was more evident at low temperatures (40-50 °C) with effective diffusivity ranging from 10.85 × 10-9 to 12.30 × 10-9 m2/s. The Midilli and Page models efficiently predicted the drying kinetics.


Fibre size does not appear to influence the ease of enzymatic hydrolysis of organosolv-pretreated softwoods.
To determine the effect of fibre size on enzymatic hydrolysis, organosolv-pretreated lodgepole pine was size-fractionated into six substrates ranging in average size from 0.20 to 3.4mm. Other than the fines fraction (<0.2mm) which contained most of the lignin, the fractionated substrates were more readily hydrolyzed than the original substrate with nearly complete hydrolysis after 72 h at 5 FPU g(-1) cellulose. Surprisingly, fibre size was found to have little influence on enzymatic hydrolysis likely due to similarities in the substrates' chemical composition, accessible surface area, cellulose crystallinity and degree of polymerization. To determine the influence of the fines on enzymatic hydrolysis, their content was artificially increased (from 8.9% to 55.4%) however; this did not have a noticeable effect. These results show that within the range of fibre sizes tested, other substrate characteristics likely play a more significant role in the ease of hydrolysis of pretreated substrates.


[Giardia duodenalis and its involvement in skin diseases].
Over the last thirty years, the scientific community has become increasingly interested in the intestinal flora, whether commensal or pathogenic, and its impact on other organs. In dermatology, the correlation between intestinal microbial agents and cutaneous lesions is well established. Giardia duodenalis, an intestinal parasite, has been particularly widely studied. The aim of this work is to provide a review of studies demonstrating the involvement of G. duodenalis in various forms of dermatosis. The data were obtained by an English-language literature search of Medline, PubMed and Google Scholar for the period 1975-2015. Among the thirty case reports since 1976, we selected the twenty most objective and clinically relevant. This review demonstrates that intestinal giardiasis may be an etiological factor, either alone or in combination with other agents, of various dermatoses through inflammatory and allergic mechanisms or intestinal hyperpermeability. The mucocutaneous lesions are varied: urticaria, angioedema, atopic dermatitis, erythema nodosum, Wells syndrome, among others. The role and origin of the infection are often unknown, and it is thus difficult to determine the interval between parasite infestation and the onset of skin lesions. Consequently, a fecal examination to identify G. duodenalis should be considered in chronic urticaria or angioedema, and where atopic dermatitis occurs in adulthood without any specific etiology. Therapeutic test should be done in every suspicion.


Depletion of non specific esterase activity in the colonic mucosa of patients with ulcerative colitis.
Non specific esterases (NSE) are a group of cellular carboxylesterases, enzyme markers of monocytes/macrophages, whose tissue distribution in the human body and changes in various disease states have not been adequately studied. We investigate the presence and localization of NSE, in the normal and inflamed human colonic mucosa. NSE were studied histochemically and biochemically using alpha-naphthyl acetate as the substrate, in the colonic mucosa from 67 patients with colitis of various aetiologies and 10 normal controls. In addition, esterase activity was studied biochemically in serum from colitic patients and normal controls. Histochemical study of the colonic tissue demonstrated that NSE were localised in the epithelial brush border, the goblet cells of the glands and a macrophage population of the lamina propria in the colonic mucosa of normal controls and patients with non specific colitis. In active ulcerative colitis, esterase depletion and esterase negative macrophages were identified in parallel with goblet cell disappearance. Gradual reappearance of esterase activity was found after successful treatment. Biochemical study of NSE activity showed that serum and colonic tissue esterase levels were greatly (P < 0.001) reduced in active ulcerative colitis compared to the normal controls or non specific colitis patients and they were increased after successful treatment. Despite this increase, the esterase activity in the colonic tissue from ulcerative colitis patients after treatment was significantly reduced compared to the normal controls. Interestingly, the enzyme levels from non-inflamed areas of the bowel of patients with ulcerative colitis were also significantly (P < 0.01) decreased compared to the normal controls. These data suggest that esterase reduction in ulcerative colitis is not a simple result of the inflammatory process but rather it precedes its development. This enzyme depletion might have an important pathogenetic implication in the inflammatory process.


Leveraging Joint Mechanics Simplifies the Neural Control of Movement.
Behaviors we perform each day, such as manipulating an object or walking, require precise control of the interaction forces between our bodies and the environment. These forces are generated by muscle contractions, specified by the nervous system, and by joint mechanics, determined by the intrinsic properties of the musculoskeletal system. Depending on behavioral goals, joint mechanics might simplify or complicate control of movement by the nervous system. Whether humans can exploit joint mechanics to simplify neural control remains unclear. Here we evaluated if leveraging joint mechanics simplifies neural control by comparing performance in three tasks that required subjects to generate specified torques about the ankle during imposed sinusoidal movements; only one task required torques that could be generated by leveraging the intrinsic mechanics of the joint. The complexity of the neural control was assessed by subjects' perceived difficulty and the resultant task performance. We developed a novel approach that used continuous estimates of ankle impedance, a quantitative description of the joint mechanics, and measures of muscle activity to determine the mechanical and neural contributions to the net ankle torque generated in each task. We found that the torque resulting from changes in neural control was reduced when ankle impedance was consistent with the task being performed. Subjects perceived this task to be easier than those that were not consistent with the impedance of the ankle and were able to perform it with the highest level of consistency across repeated trials. These results demonstrate that leveraging the mechanical properties of a joint can simplify task completion and improve performance.


Some 1,2-diaminobenzene derivatives as reagents for gas chromatographic determination of selenium with an electron-capture detector.
1,2-Diaminobenzene and its derivatives react with selenous acid in acidic solution to form the piazselenols, which can be extracted into toluene. Microgram amounts of selenium can be determined spectrophotometrically by measuring the absorbance of these piazselenols extracted into toluene. A more sensitive method, in which the piazselenols extracted into toluene are detected by electron-capture gas chromatography, has been developed. In order to find a more sensitive reagent, 13 piazselenols were synthesized. The retention behaviour and sensitivity in electron-capture detection gas chromatography and the distribution ratios between aqueous solution and toluene were studied for each piazselenol extracted into toluene. Of these piazselenols, 4,6-dibromopiazselenol, formed by the reaction of 1,2-diamino-3,5-dibromobenzene with selenous acid, was found to be best as regards sensitivity and distribution ratio. Under the optimal conditions for the formation and the extraction of the piazselenol, the practical detection limit was 1 ng. Selenium(VI) and total selenium in NBS Bovine Liver, SRM 1577, were determined successfully.


The World Health Organization defines hormone replacement therapy as carcinogenic: is this plausible?
In June 2005 the World Health Organization's International Agency for Research on Cancer (IARC) classified combined hormone contraception and menopausal therapy as carcinogenic in humans. The IARC's function is to identify potential carcinogens associated with nutrition, environment and pharmaceutical products. They do not produce risk-benefit analyses for any country or population. Their conclusions are highly controversial in that no proof is presented for a causal relationship of estrogens with reproductive cancer, be it plausibility according to mechanisms of action or experimental evidence in an animal model. Equating natural compounds like estradiol with defined carcinogens like asbestos, tobacco smoke as well as indispensable drugs such as aspirin and tamoxifen is of no substantial clinical relevance. Thus, there are no new reasons to change current management principles with combination hormone contraception and therapy.


Growth and metabolism of human tumor kidney cells on galactose and glucose.
The culture kinetics of human tumor kidney cells (TCL 598) grown on microcarriers are compared with media initially supplemented with either glucose alone or a mixture of galactose and glucose. Growth rates and maximal cell densities are similar, but cellular death is much slower in galactose than in glucose. Galactose is metabolized at a much slower specific rate than glucose. Cells grown in the galactose medium show a different pattern of lactate and pyruvate metabolism compared to cells grown in the glucose medium. Growth with galactose also favours oxidation of glutamine to alanine.


The composition and metabolism of high density lipoprotein subfractions.
The composition and metabolism of high density lipoprotein (HDL) subfractions were investigated in seven normal individuals. Mean HDL2 (d, 1.063-1.125 g/ml) composition (by weight) was 43% protein, 28% phospholipid, 23% cholesterol, and 6% triglyceride, and mean HDL3 (d, 1.125-1.21 g/ml) composition was 58% protein, 22% phospholipid, 14% cholesterol, and 5% triglyceride. The mean apoA-I; apoA-II weight ratio was 4.75 for HDL2 and 3.65 for HDL3. HDL2 protein was proportionally slightly richer in C apolipoproteins and higher molecular weight constituents (including apoE) than HDL3. Kinetic studies utilized radiolabeled HDLA (d, 1.09-1.21 g/ml), HDL2, and HDL3 demonstrated rapid exchange of apoA-I and apoA-II radioactivity among HDL subfractions, similar fractional rates of catabolism of apoA-I and apo A-II within HDL, and similar radioactivity decay within HDL subfractions. Mean plasma residence time was 5.74 days for radiolabeled HDL2 and 5.70 days for radiolabedled HDL3. Differences in HDL protein mass among individuals were largely due to alterations in catabolism, and in general both HDL2 and HDL3 were catabolized via a plasma and a nonplasma pathway. Data from simultaneous radiolabeled very low density lipoprotein and HDL studies in 2 individuals are consistent with the concept that apoC-II and apoC-III are catabolized at a different rate than are apo A-I and apo A-II within the HDL density range.


Diagnostic work-up in acute conditions of inborn errors of metabolism and storage diseases.
Inborn errors of metabolism may present with acute neurological symptoms at any age. However, especially in neonates and infants, these conditions may be acute and if untreated may lead to permanent cerebral lesions or to death. Knowledge of the main signs and symptoms of these conditions may be lifesaving, especially for conditions that are treatable. From the pathophysiological perspective, errors of metabolism can be divided into disorders causing "intoxication," disorders impairing energy production, and disorders involving complex molecules. From the clinical perspective, errors of metabolism may present with acute symptoms in the neonatal period and early infancy; late-onset acute and recurrent attacks; chronic and progressive symptoms. Nonspecific readily available biochemical markers may suggest the underlying condition but in most cases the choice of appropriate biochemical and molecular tests is required to establish the diagnosis. Progress in the treatment of inborn errors of metabolism has been slower than progress in diagnostic methods and in understanding of the pathophysiology of these disorders. Nevertheless, outcomes are improving with the use of dialysis and drugs to promote the removal of toxic metabolites and measures to keep catabolism to a minimum. Early intervention is crucial when neurological sequelae could be avoided, which requires constant vigilance and routine measurement of diagnostic biochemical markers in suspected cases.


An integrated analysis of gut microbiota and the brain transcriptome reveals host-gut microbiota interactions following traumatic brain injury.
Recent evidence suggests that there is a link between gut and brain via microbial, immune, endocrine and neural signaling pathways, but the changes of gut-brain axis following brain trauma has not yet been clearly shown. The aim of this study was to reveal the gut microbiota and transcriptomic profile of the cerebral cortex in traumatic brain injury (TBI) mice. A controlled cortical impact (CCI) device was used to establish a TBI model. Behavioral testing and histopathological analysis were performed. The gut microbiota was analyzed by 16S rRNA sequencing, and gene expression in the cerebral cortex was detected by whole-transcriptome sequencing (RNA-Seq) 7 days after TBI. The analysis of 16S rRNA sequencing data indicated that TBI increased the relative abundance of Bifidobacterium. The TBI group showed a disturbance in intestinal flora. RNA-Seq analysis identified 523 differentially expressed genes (481 upregulated and 42 downregulated) in the cerebral cortex of the TBI group compared with the sham group. Cluster analysis revealed 93 immune system process-related genes and 55 inflammatory response-related genes that were differentially expressed. This manuscript reports pathogenic changes via the gut-brain axis driven by TBI, which confer persistent symptoms and susceptibility to neurodegeneration.


The association of BRAF V600E gene mutation with proliferative activity and histopathological characteristics of congenital melanocytic nevi in children.
A lot of congenital melanocytic nevi (CMN) carry the somatic mutation in the oncogene BRAF V600E. But the detailed histopathologic characteristics and the proliferative activity of CMN with BRAF V600E gene mutation have not been systematically documented. To identify the proliferative activity and histopathological features correlating them with BRAF V600E gene mutation status in CMN. CMN were retrospectively identified from the laboratory reporting system. Mutations were determined by Sanger sequencing. The CMN were divided into a mutant group and control group according to whether there was BRAF gene mutation and were strictly matched according to gender, age, nevus size, and location. Histopathological analysis, analysis of Ki67 expression by immunohistochemistry and laser confocal fluorescence microscopy were performed. The differences in Ki67 index, the depth of nevus cell involvement and the number of nevus cell nests between the mutant group and the control group was statistically significant, with p-values of 0.041, 0.002 and 0.007, respectively. Compared with BRAF V600E negative nevi, BRAF V600E positive nevi often exhibited predominantly nested intraepidermal melanocytes, and larger junctional nests, but the difference in this data sets were not statistically significant. The number of nests (p = 0.001) was positively correlated with the proportion of Ki67 positive cells. A small sample of patients were included and there was no follow-up. BRAF V600E gene mutations were associated with high proliferative activity and distinct histopathological features in congenital melanocytic nevi.


Predictors of female genital organ involvement in radical cystectomy for urothelial carcinoma of the bladder: A single-center retrospective analysis of 112 female patients.
To evaluate predictors of organ involvement and oncological outcomes after radical cystectomy with anterior exenteration in female patients. Among 1198 patients who underwent radical cystectomy for the bladder tumor between 1990 and 2015, 178 (14.9%) patients were female. They were divided into two groups according to pelvic involvement in pathology. Their medical records and pathology and image findings were reviewed retrospectively. Non-urothelial cell carcinoma and no genital organ pathology were excluded. Multivariate logistic regression was performed to predict factors associated with female organ involvement. Out of 112 eligible female patients with urothelial cell carcinoma, 11 (9.8%) had female genital organ involvement. Female genital organ involvement occurred primarily in the uterus (63.6%) mostly. The 5-year overall survival rates were 67.3% in the non-involvement group and 18.9% in the involvement group. On multivariate analysis Tumor location of trigone or bladder neck at transurethral resection of bladder tumor (TUR-B) (odds ratio [OR] 19.84, 95% confidence interval [CI] 2.89-230.68, p = 0.0056), maximum tumor size at computed tomography (CT) (OR 2.17, 95% CI 1.29-4.34, p = 0.0095), and hydronephrosis at CT (OR 17.61, 95% CI 2.28-296.26, p = 0.0158) were associated with female organ involvement. Tumor location of trigone or bladder neck at TUR-B, maximum tumor size at CT or hydronephrosis at CT were significant factors to predict female genital organ involvement. Preoperative recognition of female genital organ involvement could increase the decision to perform genital organ-sparing surgeries.


Naja melanoleuca cobra venom contains two forms of complement-depleting factor (CVF).
Two forms of complement-depleting cobra venom factor (CVFm1 and CVFm2), possessing molecular masses of 142.6 kDa (CVFm1) and 143.1 kDa (CVFm2), according to MALDI mass-spectrometry, were isolated from the Naja melanoleuca cobra venom. As shown by polyacrylamide gel electrophoresis in the presence of SDS, both forms similarly to factor from the Naja kaouthia cobra venom (CVFk) consist of three polypeptide chains with molecular masses of about 70, 50, and 30 kDa, the two large subunits being glycosylated. As determined by MALDI mass-spectrometry, 30 kDa subunits of CVFm1 and CVFm2 have considerably different finger-prints of tryptic digests that suggests differences in their amino acid sequences. A study of activity in vivo has shown no significant differences in C3 consumption by CVFm1, CVFm2 and CVFk in mouse blood. However, as shown by an immunoassay method, they differ in their ability to activate the complement system via C3 conversion, the ratio of these activities for CVFm1:CVFm2:CVFk being 2.5:1.6:1. Kinetic studies using a hemolytic test showed that complement depletion by CVFm1 is faster than that by CVFm2. Thus, for the first time the presence in a single venom of two forms of CVF differing by both amino acid sequence and biological activity has been shown.


Battling back from childhood sexual abuse and surviving the journey.
The experience of childhood sexual abuse can be so profound that it fundamentally alters one's development and personality. Avoidance, repression, denial, and rationalization are some defense mechanisms used by the victims to deal with the abuse. Nurses working with a patient with a history of childhood sexual abuse must help the patient discover his or her own personal meaning of the abuse.


Oculomotor disturbances associated with 5-fluorouracil chemotherapy.
Two patients treated with 5-fluorouracil (5-FU) for disseminated adenocarcinoma of the colon developed cerebellar dysfunction typical of 5-FU neurotoxicity. The neurotoxicity was associated with oculomotor disturbances expressed primarily as weakness of convergence and divergence. Detailed postmortem examination of one patient revealed no anatomical abnormalities of the central nervous system. The ocular motor disturbances are probably an expression of regional 5-FU neurotoxicity primarily affecting the brain stem.


Artificial high birefringence in all-dielectric gradient grating for broadband terahertz waves.
Subwavelength dielectric gratings are widely applied in the phase and polarization manipulation of light. However, the dispersion of the normal dielectric gratings is not flat while their birefringences are not enough in the THz regime. In this paper, we have fabricated two all-dielectric gratings with gradient grids in the THz regime, of which artificial birefringence is much larger than that of the equal-grid dielectric grating demonstrated by both experiments and simulations. The transmission and dispersion characteristics are also improved since the gradient grids break the periodicity of grating lattices as a chirp feature. From 0.6-1.4 THz, a broadband birefringence reaches 0.35 with a low dispersion and good linearity of phase shift, and the maximum phase shift is 1.4π. Furthermore, these gradient gratings are applied as half-wave plates and realize a linear polarization conversion with a conversion rate over 99%, also much higher than the equal-grid gratings. These gradient gratings show great advantages compared to the periodic gratings and provide a new way in the designing of artificial birefringence material.


State of polybrominated diphenyl ethers in China: an overview.
Polybrominated diphenyl ethers (PBDEs), extensively used as flame retardants, are ubiquitous environmental contaminants that are found in both abiotic and biotic environmental samples. Sufficient evidence shows that PBDEs have been rapidly accumulating in the environment of China, especially in the Southeast regions. This paper summarizes and critically reviews the published scientific data on PBDEs in China, including the levels of PBDEs in the air, soil, water, sediment, the terrestrial and marine organisms, and human samples in China. The data preliminarily reveal the state of PBDEs in China.


Base-base interactions in nucleic acids containing A-T base pairs. Structure of poly[d(A-T)].
The Watson-Crick type of base pairing is considered to be mandatory for the formation of duplex DNA. However, conformational calculations carried out in our laboratory, have shown that some combinations of backbone torsion angles and sugar pucker lead to duplexes with Hoogsteen type of base pairing also. Here we present the results of energy calculations performed on A-T containing doublet sequences in the D-form with both Hoogsteen and Watson-Crick type of base pairing and the 3 viable models for the A-T containing polynucleotide duplex poly[d(A-T)].


Phosphatases in plants.
Reversible protein phosphorylation is an essential posttranslational modification mechanism executed by opposing actions of protein phosphatases and protein kinases. About 1,000 predicted kinases in Arabidopsis thaliana kinome predominate the number of protein phosphatases, of which there are only ~150 members in Arabidopsis. Protein phosphatases were often referred to as "housekeeping" enzymes, which act to keep eukaryotic systems in balance by counteracting the activity of protein kinases. However, recent investigations reveal the crucial and specific regulatory functions of phosphatases in cell signaling. Phosphatases operate in a coordinated manner with the protein kinases, to execute their important function in determining the cellular response to a physiological stimulus. Closer examination has established high specificity of phosphatases in substrate recognition and important roles in plant signaling pathways, such as pathogen defense and stress regulation, light and hormonal signaling, cell cycle and differentiation, metabolism, and plant growth. In this minireview we provide a compact overview about Arabidopsis protein phosphatase families, as well as members of phosphoglucan and lipid phosphatases, and highlight the recent discoveries in phosphatase research.


Dietary ellagic acid supplementation attenuates intestinal damage and oxidative stress by regulating gut microbiota in weanling piglets.
Intestinal oxidative stress triggers gut microbiota dysbiosis, which is involved in the etiology of post-weaning diarrhea and enteric infections. Ellagic acid (EA) can potentially serve as an antioxidant supplement to facilitate weaning transition by improving intestinal oxidative stress and gut microbiota dysbiosis. Therefore, we aimed to investigate the effects of dietary EA supplementation on the attenuation of intestinal damage, oxidative stress, and dysbiosis of gut microbiota in weanling piglets. A total of 126 piglets were randomly assigned into 3 groups and treated with a basal diet and 2 mL saline orally (Ctrl group), or the basal diet supplemented with 0.1% EA and 2 mL saline orally (EA group), or the basal diet and 2 mL fecal microbiota suspension from the EA group orally (FEA group), respectively, for 14 d. Compared with the Ctrl group, EA group improved growth performance by increasing average daily feed intake and average daily weight gain (P < 0.05) and decreasing fecal scores (P < 0.05). EA group also alleviated intestinal damage by increasing the tight junction protein occludin (P < 0.05), villus height, and villus height-to-crypt depth ratio (P < 0.05), while decreasing intestinal epithelial apoptosis (P < 0.05). Additionally, EA group enhanced the jejunum antioxidant capacity by increasing the total antioxidant capacity (P < 0.01), catalase (P < 0.05), and glutathione/oxidized glutathione (P < 0.05), but decreased the oxidative metabolite malondialdehyde (P < 0.05) compared to the Ctrl group. Compared with the Ctrl group, EA and FEA groups increased alpha diversity (P < 0.05), enriched beneficial bacteria (Ruminococcaceae and Clostridium ramosum), and increased metabolites short-chain fatty acids (P < 0.05). Correspondingly, FEA group gained effects comparable to those of EA group on growth performance, intestinal damage, and intestinal antioxidant capacity. In addition, the relative abundance of bacteria shifted in EA and FEA groups was significantly related to the examined indices (P < 0.05). Overall, dietary EA supplementation could improve growth performance and attenuate intestinal damage and oxidative stress by regulating the gut microbiota in weanling piglets.


Long-Term Ambient Air Pollution Exposures and Brain Imaging Markers in Korean Adults: The Environmental Pollution-Induced Neurological EFfects (EPINEF) Study.
Only a limited number of neuroimaging studies have explored the effects of ambient air pollution in adults. The prior studies have investigated only cortical volume, and they have reported mixed findings, particularly for gray matter. Furthermore, the association between nitrogen dioxide (NO2) and neuroimaging markers has been little studied in adults. We investigated the association between long-term exposure to air pollutants (NO2, particulate matter (PM) with aerodynamic diameters of ≤10μm (PM10) and ≤2.5μm (PM2.5), and neuroimaging markers. The study included 427 men and 530 women dwelling in four cities in the Republic of Korea. Long-term concentrations of PM10, NO2, and PM2.5 at residential addresses were estimated. Neuroimaging markers (cortical thickness and subcortical volume) were obtained from brain magnetic resonance images. A generalized linear model was used, adjusting for potential confounders. A 10-μg/m3 increase in PM10 was associated with reduced thicknesses in the frontal [-0.02mm (95% CI: -0.03, -0.01)] and temporal lobes [-0.06mm (95% CI: -0.07, -0.04)]. A 10-μg/m3 increase in PM2.5 was associated with a thinner temporal cortex [-0.18mm (95% CI: -0.27, -0.08)]. A 10-ppb increase in NO2 was associated with reduced thicknesses in the global [-0.01mm (95% CI: -0.01, 0.00)], frontal [-0.02mm (95% CI: -0.03, -0.01)], parietal [-0.02mm (95% CI: -0.03, -0.01)], temporal [-0.04mm (95% CI: -0.05, -0.03)], and insular lobes [-0.01mm (95% CI: -0.02, 0.00)]. The air pollutants were also associated with increased thicknesses in the occipital and cingulate lobes. Subcortical structures associated with the air pollutants included the thalamus, caudate, pallidum, hippocampus, amygdala, and nucleus accumbens. The findings suggest that long-term exposure to high ambient air pollution may lead to cortical thinning and reduced subcortical volume in adults. https://doi.org/10.1289/EHP7133.


Fasting insulin concentration is highly correlated with quantitative insulin sensitivity check index.
Given that the "gold standard" method for evaluating insulin sensitivity in vivo (hyperinsulinemic euglycemic glucose clamp technique) cannot be routinely applied because of technical reasons, simple methods and indexes were developed and are currently available to assess insulin sensitivity in vivo. Quantitative insulin sensitivity check index (QUICKI) has recently been described and is able to accurately estimate insulin sensitivity from a fasting blood sample. We demonstrated that fasting insulin levels strongly inversely correlated with QUICKI in three different groups: 215 healthy nondiabetic nonobese subjects, 62 nondiabetic obese subjects, and 44 patients with glucose intolerance or type 2 diabetes mellitus. Fasting insulin measurement is a simple way of assessing insulin sensitivity in obese and nonobese humans, with or without glucose intolerance or type 2 diabetes mellitus.


Perilymph fistula: fifty years of controversy.
Perilymph fistula (PLF) is defined as a leak of perilymph at the oval or round window. It excludes other conditions with "fistula" tests due to a dehiscent semi circular canal from cholesteatoma and the superior canal dehiscence syndrome. It was first recognized in the early days of stapedectomy as causing disequilibrium and balance problems before sealing of the stapedectomy with natural tissue became routine. It then became apparent that head trauma and barotraumatic trauma from flying or diving could be a cause of PLF. Descriptions of "spontaneous" PLF with no trauma history followed. A large literature on PLF from all causes accumulated. It became an almost emotional issue in Otolaryngology with "believers" and "nonbelievers." The main criticisms are a lack of reliable symptoms and diagnostic tests and operative traps in reliably distinguishing a perilymph leak from local anaesthetic. There are extensive reviews on the whole topic, invariably conveying the authors' own experiences and their confirmed views on various aspects. However, a close examination reveals a disparity of definitions and assumptions on symptoms, particularly, vestibular. This is an intentionally provocative paper with suggestions on where some progress might be made.


Supernormality: recent developments.
The major advance in our understanding of supernormality is the following hypothesis. Focal accumulations of extruded potassium ion in unstirred-clefts (invaginated extensions of the extracellular space in Purkinje fibers) cause threshold to fall by virtue of the early effects of hyperkalemia: lowering of threshold and acceleration of conduction. These effects rapidly dissipate in diastole as ionic equilibration takes place; threshold rises and assumes its late diastolic value. It is not known if this mechanism is applicable to the supernormality of specialized atrial fibers. Comparing the strength interval curves of supernormality and triggered automaticity the fall in threshold during the upstroke of the late after-depolarisation occurs later than the supernormal phase and is followed by a threshold rise (during the downstroke of the after-potential). Supernormality does not correspondingly show this biphasic change in the strength interval curve.


Enhancement of natural killer cell activity and 2-5A synthetase in mice treated with polyadenylic.polyuridylic acid.
Previous studies have demonstrated that splenic natural killer (NK) cell activity of mice can be efficiently enhanced by polyadenylic.polyuridylic acid [poly(A).poly(U)]. Moreover, inoculation of mice with the duplex leads to the production of interferon (IFN). The NK boosting effect in mice was analyzed in parallel with the assay of an enzyme marker for the production and action of IFN, pppA(2'p5'A)n synthetase (2-5A synthetase). Kinetic studies revealed that splenic mononuclear cells of C3H/He mice inoculated intravenously with 10 micrograms or more of poly(A).poly(U) showed significantly enhanced cytotoxic activity in an in vitro 51Cr-release assay using NK sensitive YAC-1 target cells. Intravenous, intraperitoneal, and intramuscular administration of the duplex into mice were equally effective in obtaining such NK boosting effect. Furthermore, repeated weekly injections of poly(A).poly(U) did not induce resistance against NK boosting in the organisms. The levels of 2-5A synthetase in the organs, particularly spleens, of mice inoculated similarly with poly(A).poly(U) were greatly increased with a dose-dependent pattern. Repeated injections of mice with the duplex at 4-day intervals resulted also in significantly enhanced levels of splenic 2-5A synthetase after each injection. Thus, as a whole, enhanced NK activity accompanied increased levels of 2-5A synthetase in mice treated with poly(A).poly(U).


Convergent evolution in structural elements of proteins investigated using cross profile analysis.
Evolutionary relations of similar segments shared by different protein folds remain controversial, even though many examples of such segments have been found. To date, several methods such as those based on the results of structure comparisons, sequence-based classifications, and sequence-based profile-profile comparisons have been applied to identify such protein segments that possess local similarities in both sequence and structure across protein folds. However, to capture more precise sequence-structure relations, no method reported to date combines structure-based profiles, and sequence-based profiles based on evolutionary information. The former are generally regarded as representing the amino acid preferences at each position of a specific conformation of protein segment. They might reflect the nature of ancient short peptide ancestors, using the results of structural classifications of protein segments. This report describes the development and use of "Cross Profile Analysis" to compare sequence-based profiles and structure-based profiles based on amino acid occurrences at each position within a protein segment cluster. Using systematic cross profile analysis, we found structural clusters of 9-residue and 15-residue segments showing remarkably strong correlation with particular sequence profiles. These correlations reflect structural similarities among constituent segments of both sequence-based and structure-based profiles. We also report previously undetectable sequence-structure patterns that transcend protein family and fold boundaries, and present results of the conformational analysis of the deduced peptide of a segment cluster. These results suggest the existence of ancient short-peptide ancestors. Cross profile analysis reveals the polyphyletic and convergent evolution of β-hairpin-like structures, which were verified both experimentally and computationally. The results presented here give us new insights into the evolution of short protein segments.


Exploration of serum sensitive biomarkers of fatty liver in dairy cows.
Serum proteins are sensitive with diseases in dairy cows, and some of them could be used as biomarkers for fatty liver. This study aimed to explore serum biomarkers for fatty liver in dairy cows. A total of 28 early lactating dairy cows were chosen from a commercial dairy herds, liver samples were collected for determining concentration of triacylglycerol (TAG), and serum samples were collected for measuring fibroblast growth factor-21 (FGF-21), adiponectin, Lipoprotein-associated phospholipase A2 (LP-PLA2), and hemoglobin (Hb). Dairy cows were divided into fatty liver (liver TAG > 5%, wet weight) and control group (liver TAG < 5%, wet weight). Concentration of FGF-21 was greater in fatty liver cows, while the concentration of LP-PLA2 and Hb was less. The concentration of FGF-21 and total Hb had strong correlation with the liver TAG as well as good prediction power (kappa value = 0.79 and 0.58, respectively). These results suggested that the serum concentration of FGF-21 and total Hb could be potentially used as fatty liver biomarkers in lactating dairy cows.


Sodium citrate and biochar synergistic improvement of nanoscale zero-valent iron composite for the removal of chromium (Ⅵ) in aqueous solutions.
Sodium citrate (SC) is a widely-used food and industrial additive with the properties of complexation and microbial degradation. In the present study, nano-zero-valent iron reaction system (SC-nZVI@BC) was successfully established by modifying nanoscale zero-valent iron (nZVI) with SC and biochar (BC), and was employed to remove Cr(Ⅵ) from aqueous solutions. The nZVI, SC-nZVI and SC-nZVI@BC were characterized and compared using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analyses (TGA), vibrating sample magnetometer (VSM), scanning electron microscope (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The results showed that nZVI was successfully loaded on the biochar, and both the agglomeration and surface passivation problems of nanoparticles were well resolved. The dosage of SC, C:Fe, initial pH and Cr(Ⅵ) concentration demonstrated direct effects on the removal efficiency. The maximum Cr(Ⅵ) removal rate and the removal capacity within 60 min were 99.7% and 199.46 mg/g, respectively (C:Fe was 1:1, SC dosage was 1.12 mol.%, temperature was 25°C, pH = 7, and the original concentration of Cr(Ⅵ) was 20 mg/L). The reaction confirmed to follow the pseudo-second-order reaction kinetics, and the order of the reaction rate constant k was as follows: SC-nZVI@BC > nZVI@BC > SC-nZVI > nZVI. In addition, the mechanism of Cr(Ⅵ) removal by SC-nZVI@BC mainly involved adsorption, reduction and co-precipitation, and the reduction of Cr(Ⅵ) to Cr(Ⅲ) by nano Fe0 played a vital role. Findings from the present study demonstrated that the SC-nZVI@BC exhibited excellent removal efficiency toward Cr(Ⅵ) with an improved synergistic characteristic by SC and BC.


Involvement of the skull base and vault in chronic idiopathic hyperphosphatasia.
Chronic idiopathic hyperphosphatasia (CIH) is a rare generalised skeletal dysplasia in childhood. The clinical, radiographic and cerebral MR findings in a 5-year-old girl with the severe infantile form of CIH are reported. In spite of cranial enlargement, the intracranial space and the skull base were markedly reduced, the whole brain was compressed and a Chiari I malformation was present. Normal flow in the dural venous sinuses was documented. The patient showed no detectable cranial nerve involvement or hydrocephalus. Cranial MR in this patient enabled us to confirm that CIH involves the skull base and vault.


Novel metallo-β-lactamases inhibitors restore the susceptibility of carbapenems to New Delhi metallo-lactamase-1 (NDM-1)-harbouring bacteria.
The production of metallo-β-lactamases is a major mechanisms adopted by bacterial pathogens to resist carbapenems. Repurposing approved drugs to restore the efficacy of carbapenems represents an efficient and cost-effective approach to fight infections caused by carbapenem resistant pathogens. The nitrocefin hydrolysis assay was employed to screen potential New Delhi metallo-lactamase-1 (NDM-1) inhibitors from a commercially available U.S. Food and Drug Administration (FDA) approved drug library. The mechanism of inhibition was clarified by metal restoration, inductively coupled plasma mass spectrometry (ICP-MS) and molecular dynamics simulation. The in vitro synergistic antibacterial effect of the identified inhibitors with meropenem was determined by the checkerboard minimum inhibitory concentration (MIC) assay, time-dependent killing assay and combined disc test. Three mouse infection models were used to further evaluate the in vivo therapeutic efficacy of combined therapy. Twelve FDA-approved compounds were initially screened to inhibit the ability of NDM-1 to hydrolyse nitrocefin. Among these compounds, dexrazoxane, embelin, candesartan cilexetil and nordihydroguaiaretic acid were demonstrated to inhibit all tested metallo-β-lactamases and showed an in vitro synergistic bactericidal effect with meropenem against metallo-β-lactamases-producing bacteria. Dexrazoxane, embelin and candesartan cilexetil are metal ion chelating agents, while the inhibition of NDM-1 by nordihydroguaiaretic acid involves its direct binding to the active region of NDM-1. Furthermore, these four drugs dramatically rescued the treatment efficacy of meropenem in three infection models. Our observations indicated that dexrazoxane, embelin, candesartan cilexetil and nordihydroguaiaretic acid are promising carbapenem adjuvants against metallo-β-lactamases-positive carbapenem resistant bacterial pathogens.


The risk of intentional dissolution of the smear layer after mechanical preparation of root canals.
The root canals of 27 caries-free human cuspids were divided into 3 groups of 9 teeth each. Group I was mechanically prepared with reamers and files. Alternate irrigation with 5.25% NaOCl and 3% hydrogen peroxide was used between each instrument. The group II root canals were prepared with the use of alternate irrigation with the same concentrations of NaOCl and hydrogen peroxide and finally flushed with 17% EDTA and NaOCl solution. Group III was prepared mechanically with the use of sterile distilled water as an irrigant followed by a final flush with 17% EDTA solution. The root canals of all specimens were obturated with gutta-percha points and Tubliseal by means of the lateral condensation technique. After the root canals were obturated, samples of each of the three groups were immersed in separate flasks containing Streptococcus mutans, Staphylococcus epidermidis, and Corynebacterium hofmannii. All the microorganisms tested invaded the coronal dentin--where the access cavity had been sealed with Fynal--and/or the main foramen.


Efficacy and safety of oxaliplatin and docetaxel in patients with locally advanced and metastatic non-small-cell lung cancer (NSCLC).
Platinum-based doublets are recommended as treatment for advanced or metastatic non-small-cell lung cancer (NSCLC); however, chemotherapy must be tailored to limit side effects. A phase II study was conducted to evaluate the efficacy and safety of oxaliplatin combined with docetaxel for NSCLC. Patients with stage IIIB or IV, chemotherapy-naive NSCLC received docetaxel 70 mg/m(2), oxaliplatin 130 mg/m(2), and pegfilgrastim 6 mg every 21 days for up to six cycles. Primary endpoint was overall response rate (ORR), secondary endpoints were progression-free (PFS) and overall survival (OS), and safety. Twenty-nine patients were treated; 93% had stage IV disease and 28% had brain metastases. In 27 evaluable patients with follow-up, there were 10 partial responses for an ORR of 37% (90% confidence interval [CI], 22-55%). Median PFS was 4.6 months (95% CI, 2.6-6.5 months); 12-month PFS was 14.8% (95% CI, 3.4-34.0%). Median OS was 10.9 months (95% CI, 8.9-16.8 months); 12-month OS was 40% (95% CI, 19-61%) and 18-month OS was 16% (95% CI, 1-46%). In 29 treated patients, there were no unusual or unexpected adverse events. The most common grade 3 and 4 toxicities were anemia (14% of patients) and hyperglycemia (10%); there were only two reports of neutropenia; both were grade 1 or 2. These phase II findings suggest that the combination of oxaliplatin and docetaxel is active and well tolerated, and should be further investigated as a feasible treatment alternative for patients with advanced or metastatic NSCLC.


Extrusion-based 3D printed biodegradable porous iron.
Extrusion-based 3D printing followed by debinding and sintering is a powerful approach that allows for the fabrication of porous scaffolds from materials (or material combinations) that are otherwise very challenging to process using other additive manufacturing techniques. Iron is one of the materials that have been recently shown to be amenable to processing using this approach. Indeed, a fully interconnected porous design has the potential of resolving the fundamental issue regarding bulk iron, namely a very low rate of biodegradation. However, no extensive evaluation of the biodegradation behavior and properties of porous iron scaffolds made by extrusion-based 3D printing has been reported. Therefore, the in vitro biodegradation behavior, electrochemical response, evolution of mechanical properties along with biodegradation, and responses of an osteoblastic cell line to the 3D printed iron scaffolds were studied. An ink formulation, as well as matching 3D printing, debinding and sintering conditions, was developed to create iron scaffolds with a porosity of 67%, a pore interconnectivity of 96%, and a strut density of 89% after sintering. X-ray diffracometry confirmed the presence of the α-iron phase in the scaffolds without any residuals from the rest of the ink. Owing to the presence of geometrically designed macropores and random micropores in the struts, the in vitro corrosion rate of the scaffolds was much improved as compared to the bulk counterpart, with 7% mass loss after 28 days. The mechanical properties of the scaffolds remained in the range of those of trabecular bone despite 28 days of in vitro biodegradation. The direct culture of MC3T3-E1 preosteoblasts on the scaffolds led to a substantial reduction in living cell count, caused by a high concentration of iron ions, as revealed by the indirect assays. On the other hand, the ability of the cells to spread and form filopodia indicated the cytocompatibility of the corrosion products. Taken together, this study shows the great potential of extrusion-based 3D printed porous iron to be further developed as a biodegradable bone substituting biomaterial.


Histochemical detection of monoamine oxidase and alcohol dehydrogenase activities in the Syrian hamster Harderian glands: existence of a sexual dimorphism.
Monoamine oxidase (MAO) and alcohol dehydrogenase (AD) activities were studied histochemically in the Syrian hamster Harderian gland using tryptamine as substrate and Nitroblue Tetrazolium as the final electron acceptor. No dark: light-related changes were observed. Male type I secretory cells showed an intense MAO reaction. Female type I cells exhibited a moderate MAO activity. Both male and female glands showed a moderate/intense AD-positive reaction. Male type II cells were lacking MAO and AD activities. MAO activity found in the hamster Harderian glands corresponded mainly to MAO type A since treatment with chlorgyline (0.01, 0.1 and 0.5 mM) totally inhibited it. The possible role of these two enzymes in Harderian gland indolalkylamine metabolism is discussed.


Subclones of normal clonal prolactin cells of the rat.
We recently established a clone (2B8) of normal rat prolactin cells that secretes only prolactin into the medium. When grown in the presence of thyrotrophin-releasing hormone (TRH), estradiol (E2) or arginine vasotocin (AVT), the cells show increased production of prolactin. Subclones of single cell origin were developed from 2B8 cells exposed for 1 week to TRH, E2 or TRH plus E2. These subclones differ in their response to TRH, E2 or AVT and therefore may possess different receptors for these hormones.


Corrigendum: Clinical radiomics-based machine learning versus three-dimension convolutional neural network analysis for differentiation of thymic epithelial tumors from other prevascular mediastinal tumors on chest computed tomography scan.
[This corrects the article DOI: 10.3389/fonc.2023.1105100.].


Effect of various isoflavones on lipid levels in triton-treated rats.
The isoflavone content of some commonly used legumes was determined. In Triton-WR1339-induced hyperlipidemia in male albino rats, biochanin A, formononetin and pratensein showed hypolipidemic activity, while diadzein did not, when these isoflavones were administered as individual compounds by gastric intubation.


Potential Protective Link Between Type I Diabetes and Parkinson's Disease Risk and Progression.
Epidemiological studies suggested an association between Parkinson's disease (PD) and type 2 diabetes, but less is known about type 1 diabetes (T1D) and PD. This study sought to explore the association between T1D and PD. We used Mendelian randomization, linkage disequilibrium score regression, and multi-tissue transcriptome-wide analysis to examine the association between PD and T1D. Mendelian randomization showed a potentially protective role of T1D for PD risk (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.94-0.99; P = 0.039), as well as motor (OR, 0.94; 95% CI, 0.88-0.99; P = 0.044) and cognitive progression (OR, 1.50; 95% CI, 1.08-2.09; P = 0.015). We further found a negative genetic correlation between T1D and PD (rg = -0.17; P = 0.016), and we identified eight genes in cross-tissue transcriptome-wide analysis that were associated with both traits. Our results suggest a potential genetic link between T1D and PD risk and progression. Larger comprehensive epidemiological and genetic studies are required to validate our findings. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Transfusion of apheresis PLTs from IgA-deficient donors with anti-IgA is not associated with an increase in transfusion reactions.
Passive transfer of antibodies through transfusion has been reported to cause adverse consequences. Approximately 1 in 700 individuals of Northern European ancestry lack IgA with up to 40 percent reported as having anti-IgA. Whether these antibodies when passively transfused were associated with reactions was examined. Records were reviewed to identify IgA-deficient (<0.05 mg/dL detectable IgA) apheresis PLT donors with anti-IgA. Transfusion outcomes of products from these donors were compared to outcomes of control transfusions from donors who were not IgA-deficient. Four IgA-deficient donors with anti-IgA donated a total of 25 apheresis PLT products transfused to 22 recipients. Of the transfused products, 1 (4.0%) was associated with fever that was classified as unrelated to transfusion. In the control group, 60 donors donated 78 apheresis PLT products transfused to 56 recipients. Among these, an allergic reaction was identified (1.3%). The reaction rates between both groups were not different whether the single event in the anti-IgA group was considered a reaction (chi-squared value 0.735, p = 0.3914) or considered unrelated to transfusion (chi-square value 0.324, p = 0.5694). The transfusion of products containing anti-IgA does not appear to be associated with a greater frequency of reactions.


Pharmacokinetics of the newer fluoroquinolones.
A large number of pharmacokinetic studies have been carried out using 4-quinolones in order to estimate total and renal clearance, to examine tissue penetration, to establish suitable dosage regimens and to determine the influence of kidney and liver impairment on the pharmacokinetic behaviour. Although the quinolones are poorly water soluble over the physiological pH range (6-8) they are well absorbed following oral administration. Ofloxacin is almost completely absorbed and ciprofloxacin has been shown to have an absolute bioavailability of 0.70. Plasma protein binding varies greatly from quinolone to quinolone ranging from about 10% in the case of norfloxacin to more than 90% in the case of nalidixic acid. Penetration of the quinolones into the prostate is generally good. Most quinolones, too, have been shown to penetrate blister fluid rapidly and this model has proved useful in distribution studies. Some quinolones, like ofloxacin, are excreted largely unchanged while others like pefloxacin and acrosoxacin, are almost completely metabolized. Conjugation to very water-soluble glucuronides is not common although other types of metabolites have been shown. Little information appears to have been published on the effect of liver disease on the metabolism of the quinolones. This must be an important consideration for this type of drugs which are subject to hepatic transformation. The pharmacokinetic behaviour of quinolones in patients with impaired renal function has been extensively studied. The interaction of food on the absorption does not seem to be great, there is however evidence of a drug interaction between theophylline and some of the newer quinolones. Sucralfate and antacids containing Mg2+ or (and) Al3+-ions can markedly impair the absorption of quinolone antibiotics.


Drug-Polymer Interaction, Pharmacokinetics and Antitumor Effect of PEG-PLA/Taxane Derivative TM-2 Micelles for Intravenous Drug Delivery.
A novel polymer micelle was prepared with a high drug loading, good stability, high tolerance and better anti-tumor effect. TM-2 was encapsulated in poly-block-poly (D, L-lactic acid) self-assembled micelles by the thin-film hydration method. From the critical micelle concentrations of the copolymers, particle size, drug loading and encapsulation efficiency of drug-loading micelles, the appropriate polymer material could be assessed. Comparisons between TM-2 solution and TM-2 micelles were done to evaluate the pharmacokinetics and toxicity in rats, compared with Taxol to evaluate the anti-tumor effect in mice. The optimized TM-2 micelles achieved a high drug loading (~20%) with the polymer material of PEG2k-PLA2.5k, with a particle size of 30 nm and no significant change in particle size after lyophilization. The result of pharmacokinetic experiment displayed that the half-life in vivo was obviously prolonged. The maximum tolerated dose of TM-2 micelles was approximately 25 mg/kg in rats, and the relative tumor growth rate of Taxol (15 mg/kg), TM-2 (10 mg/kg), TM-2 (15 mg/kg) and TM-2 (40 mg/kg) in mice were 49.35%, 49.14%, 36.44 and 9.98% respectively. TM-2 micelles with high drug loading increased drug solubility, improved tolerance, antitumor effects and reduced toxicity.


Validation of a novel partial resuscitative endovascular balloon occlusion of the aorta device in a swine hemorrhagic shock model: Fine tuning flow to optimize bleeding control and reperfusion injury.
Partial restoration of aortic flow during resuscitative endovascular balloon occlusion of the aorta (REBOA) is advocated by some to mitigate distal ischemia. Our laboratory has validated the mechanics and optimal partial REBOA (pREBOA) flow rates using a prototype device. We hypothesize that pREBOA will increase survival when compared with full REBOA (fREBOA) in prolonged nonoperative management of hemorrhagic shock. Twenty swine underwent placement of aortic flow probes, zone 1 REBOA placement, and 20% blood volume hemorrhage. They were randomized to either solid organ or abdominal vascular injury. The pREBOA arm (10 swine) underwent full inflation for 10 minutes and then deflation to a flow rate of 0.5 L/min for 2 hours. The fREBOA arm (10 swine) underwent full inflation for 60 minutes, followed by deflation/resuscitation. The primary outcome is survival, and secondary outcomes are serologic/pathologic signs of ischemia-reperfusion injury and quantity of hemorrhage. Two of 10 swine survived in the fREBOA group (2/5 solid organ injury; 0/5 abdominal vascular injury), whereas 7 of 10 swine survived in the pREBOA group (3/5 solid organ injury, 4/5 abdominal vascular injury). Survival was increased (p = 0.03) and hemorrhage was higher in the pREBOA group (solid organ injury, 1.36 ± 0.25 kg vs. 0.70 ± 0.33 kg, p = 0.007; 0.86 ± 0.22 kg vs. 0.71 ± 0.28 kg, not significant). Serum evidence of ischemia was greater with fREBOA, but this was not significant (e.g., lactate, 16.91 ± 3.87 mg/dL vs. 12.96 ± 2.48 mg/dL at 120 minutes, not significant). Swine treated with pREBOA that survived demonstrated trends toward lower alanine aminotransferase, lower potassium, and higher calcium. The potassium was significantly lower in survivors at 60 minutes and 90 minutes time points (5.97 ± 0.60 vs. 7.53 ± 0.90, p = 0.011; 6.67 ± 0.66 vs. 8.15 ± 0.78, p = 0.029). Calcium was significantly higher at 30 minutes, 60 minutes, and 90 minutes (8.56 ± 0.66 vs. 7.50 ± 0.40, p = 0.034; 8.63 ± 0.62 vs. 7.15 ± 0.49, p = 0.019; 8.96 ± 0.64 vs. 7.00, p = 0.028). Prolonged pREBOA at a moderate distal flow rate provided adequate hemorrhage control, improved survival, and had evidence of decreased ischemic injury versus fREBOA. Prophylactic aggressive calcium supplementation may have utility before and during the reperfusion phase.


Streamlining tablet lubrication design via model-based design of experiments.
In oral solid dosage production through direct compression powder lubrication must be carefully selected to facilitate the manufacturing of tablets without degrading product manufacturability and quality (e.g. dissolution). To do so, several semi-empirical models relating compression performance to process operating conditions have been developed. Among them, we consider an extension of the Kushner and Moore model (Kushner and Moore, 2010, International Journal Pharmaceutics, 399:19) that is useful for the purpose, but requires an extensive experimental campaign for parameters identification. This implies the preparation and compression of multiple powder blends, each one with a different lubrication extent. In turn, this translates into a considerable consumption of Active Pharmaceutical Ingredient (API), and into time-consuming experiments. We tackled this issue by proposing a novel model-based design of experiments (MBDoE) approach, which minimizes the number of optimal blends for model calibration, while obtaining statistically sound parameters estimates and model predictions. Both sequential and parallel MBDoE configurations were compared. Experimental results involving two placebo blends with different lubrication sensitivity showed that this methodology is able to reduce the experimental effort by 60-70% with respect to the standard industrial practice independently of the formulation considered and configuration (i.e. parallel vs. sequential) adopted.


Thrombin-induced DNA synthesis of cultured human dental pulp cells is dependent on its proteolytic activity and modulated by prostaglandin E2.
To clarify the roles of alpha-thrombin and prostaglandin E2 (PGE2) in the healing and inflammatory processes of dental pulp, their effects on the DNA synthesis of human pulp cells were investigated by measurement of [3H]thymidine incorporation. At a concentration range of 1 to 25 units/ml, alpha-thrombin stimulated DNA synthesis of the pulp cells by 1.5 to 2.6-fold. On the contrary, PGE2 (> 0.05 microgram/ml) suppressed DNA synthesis by 24 to 39%. Using reverse transcriptase-polymerase chain reaction, thrombin receptor mRNA expression was identified in the pulp cells. Furthermore, alpha-thrombin-induced DNA synthesis could be inhibited by antithrombin III (2 units/ml) with heparin (2 units/ml) or D-Phe-Pro-ArgCH2Cl (50 micrograms/ml). PGE2 (0.1 to 0.5 microgram/ml) also inhibited the thrombin-induced DNA synthesis by 39 to 64%. These results imply that pulp cells express the thrombin receptor that is activated by the serine protease activity of thrombin. Interactions of thrombin and PGE2 are important in modulating the inflammatory and healing processes of the pulp.


An improved method for sensitive quantification of isoprenoid diphosphates in the astaxanthin-accumulating Haematococcus pluvialis.
A sensitive method has been established to simultaneously determine the concentrations of isopentenyl pyrophosphate (IPP), geranyl diphosphate (GPP), farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP) in H. pluvialis under different environments. This method increased the extraction efficiency of isoprenoid diphosphates through releasing isoprenoid diphosphates using Tissue Lyser. This is the first report on the efficient extraction method of metabolites in H. pluvialis cells, being suitable for all algae and plants with thick cell wall. The concentrations of isoprenoid diphosphates were measured on poroshell EC-C18 column by UHPLC-MS/MS with the LODs of 0.015, 0.027, 0.022 and 0.076 pmol for DMAPP, GPP, FPP and GGPP, respectively. It is the most sensitive method for the determination of isoprenoid diphosphates in any sample to date. Using this method, the profile of isoprenoid diphosphates was analyzed and cisoid isomers of FPP and GGPP, (Z, Z)-FPP and (Z, Z, Z-GGPP) were found firstly in H. pluvialis.


Epidermal growth factor regulates intestinal glutamine uptake during total parenteral nutrition.
Sprague Dawley rats were randomised into three groups: group I (chow) were fed rat chow and water ad libitum, group II total parenteral nutrition (TPN) received a standard formula of TPN, and group III (TPN--epidermal growth factor (EGF)) received the same TPN as group II and injections of EGF (0.1 microg/gm body weight) subcutaneously twice daily. Glutamine (GLN) concentrations in tissues and blood were measured by reversed phase high performance liquid chromatography. Gut GLN extraction was calculated by dividing the difference in GLN concentrations (Conc) between the carotid artery (ART) and portal vein (PV) by the arterial concentration [(ART Conc - PV Conc)/ART Conc]. TPN induced a marked reduction of GLN concentration in tissues and blood, and also reduction of gut GLN extraction. When EGF was administered along with TPN, gut GLN concentration did not fall and gut GLN extraction was increased by 15% (TPN - EGF 1 week, P < 0.05). Arterial blood concentration of GLN was increased when TPN and EGF were used for 1 week (P < 0.05 vs control). But EGF did not prevent the GLN concentration of other tissues decreasing during TPN. Our results suggest that EGF can regulate intestinal uptake of GLN during TPN.


The chronic administration of dopamine antagonists and methamphetamine changed the [3H]-cholecystokinin-8 binding sites in the rat frontal cortex.
The specific cholecystokinin (CCK) binding in the slide-mounted tissue sections of the rat frontal cortex was measured with [3H]-CCK-8. The binding was saturable, reversible, high in affinity, and inhibited by caerulein. The chronic administration of dopamine (DA) antagonists and methamphetamine (MAP) showed a tendency to increase the [3H]-CCK-8 binding sites (Bmax) in the frontal cortex. Long-term treatments with DA antagonists led to the depletion of CCK-8 and may have caused an observed proliferation of CCK-8 receptors in the frontal cortex.


Development of resistance to ofloxacin.
As a member of the 4-quinolone group of antibacterial agents, ofloxacin shares the almost unique feature of being exempt from plasmid-borne resistance in either Gram-negative or Gram-positive bacteria. In the light of this feature, the development of resistance mediated through chromosomal mutation has been carefully studied, particularly the processes of mutation which confer resistance to levels of ofloxacin approaching those obtained at the site of infection after oral administration. With Escherichia coli strain KL16 being used as a model system, the genetics of the development of resistance to ofloxacin at least 2 mg/L have been studied. In common with many in vitro studies of the development of resistance to the newer 4-quinolones, it has been observed that the mutation frequency was extremely low (in the range 1 X 10(-10) to 1 X 10(-12) with bacteria grown under routine laboratory conditions. The resultant organisms were very slow growing, temperature sensitive and apparently auxotrophic. The mutation(s) were, however, very unstable and the mutants readily reverted to ofloxacin sensitivity in the absence of selection with ofloxacin. Subsequent studies of spontaneous mutation under growth conditions more closely related to the in vivo situation in the lumen of the gut, with limitation of oxygen supply, showed that mutation frequencies were in the order of 1 X 10(-8). Mutants obtained under these conditions displayed the same phenotype as found previously and were equally unstable. Examination of the physiology of the ofloxacin-resistant mutants has shown that they display significant metabolic defects with regard to being able to cope with environmental fluctuations.(ABSTRACT TRUNCATED AT 250 WORDS)


Proteins: Neglected active ingredients in edible bird's nest.
Edible bird's nest (EBN) is a kind of natural invigorant with a long history of consumption in Asia, especially in China. EBN is formed by mixing the saliva of swiftlets (Aerodramus) with feathers and other components during the breeding season. Proteins are the most important nutrient in EBN. By studying proteins in EBN, we can not only elucidate their components at the molecular level, but also study their bioactivities. Therefore, it is of great significance to study the proteins in EBN. Previous research on the proteins in EBN was preliminary and cursory, and no one has summarized and analyzed the proteins in EBN and correlated the bioactivities of these proteins with the biological functions of EBN. This article focused on the proteins in EBN, listed the proteins identified in different proteomic studies, and introduced the sources, structures and bioactivities of the most frequently identified proteins, including acidic mammalian chitinase, lysyl oxidase homolog 3, mucin-5AC, ovoinhibitor, nucleobindin-2, calcium-binding protein (MW: 4.5 × 104) and glucose-regulated protein (MW: 7.8 × 104). The properties of these proteins are closely related to the bioactivities of EBN. Therefore, this article can provide inspiration for further research on the efficacy of EBN.


An atomic clock with 10(-18) instability.
Atomic clocks have been instrumental in science and technology, leading to innovations such as global positioning, advanced communications, and tests of fundamental constant variation. Timekeeping precision at 1 part in 10(18) enables new timing applications in relativistic geodesy, enhanced Earth- and space-based navigation and telescopy, and new tests of physics beyond the standard model. Here, we describe the development and operation of two optical lattice clocks, both using spin-polarized, ultracold atomic ytterbium. A measurement comparing these systems demonstrates an unprecedented atomic clock instability of 1.6 × 10(-18) after only 7 hours of averaging.


Reactive arthritis at the Sydney Sexual Health Centre 1992-2012: declining despite increasing chlamydia diagnoses.
Reactive arthritis is an under-studied complication of genital Chlamydia trachomatis infection (chlamydia). We assessed trends and risk factors for reactive arthritis in a large urban sexual health clinic. Using a case-control design, data on reactive arthritis cases and controls at the Sydney Sexual Health Centre over the period 1992-2012 were extracted and multivariate analyses were performed. Trend analyses were performed on reactive arthritis diagnoses. Over the 1992-2012 study period, 85 reactive arthritis cases were diagnosed at Sydney Sexual Health Centre. The rate of reactive arthritis diagnoses decreased over time (23 in 1992-1996 to one in 2007-2011 and none in 2012), while chlamydia diagnoses increased (770 in 1992-1996 to 2257 in 2007-2011). In multivariate analysis, factors independently associated with a reactive arthritis diagnosis were: being male (adjusted odds ratio [aOR] 3.27; 95% confidence interval [CI] 1.04-10.32; p = 0.043) or born overseas (aOR 2.69; 95% CI 1.27-5.70; p = 0.010), while a past sexually transmitted infection other than chlamydia or non-gonococcal urethritis was protective (aOR 0.21; 95% CI 0.10-0.45; p < 0.001). Reactive arthritis was not associated with current or recent chlamydia infection (p = 0.184) but was marginally associated with past non-gonococcal urethritis (p = 0.080). This study found a decline in reactive arthritis diagnoses despite an increase in chlamydia diagnoses.


Studies on effect of temperature on synthesis of hierarchical TiO2 nanostructures by surfactant free single step hydrothermal route and its photoelectrochemical characterizations.
Exotic hierarchical rutile TiO2 nanostructures are synthesized by surfactant free single step hydrothermal route. The effect of reaction temperature, ranging from 140°C to 200°C on the properties of the synthesized rutile-TiO2 is investigated. The synthesized rutile-TiO2 nanostructures are characterized using X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy, UV-vis spectroscopy and scanning electron microscopy techniques. The deposited TiO2 samples are found to be photoelectrochemically active and the best photoelectrochemical performance (0.95±0.05%) is obtained for the sample deposited at 180°C. A possible temperature dependent growth mechanism resulting in photochemically active TiO2 nanostructure thin films is proposed.