Propofol protects against opioid-induced hyperresponsiveness of airway smooth muscle in a horse model of target-controlled infusion anaesthesia.
General anaesthesia in horses is associated with elevated mortality rate in subjects suffering of heaves. Target-controlled infusion (TCI) of sedative-hypnotic medications and opioids represents a total intravenous anaesthesia (TIVA) method validated in veterinary medicine. Since there are no data concerning the impact of these classes of drugs in inducing bronchial hyperresponsiveness (BHR) in horses, the aim of this study was to investigate the effect propofol and remifentanil on the contractile response of equine airway smooth muscle. The influence of propofol and remifentanil on the contractile response of equine isolated bronchi to electrical field stimulation (EFS) was assessed. The role of capsaicin-sensitive sensory nerves, inducible nitric oxide synthase (iNOS) and neurokinin 2 (NK2) receptor was also assessed. The interaction analysis was performed by Bliss Independence theory. Experiments were repeated in desensitized and passively sensitized airways. Remifentanil induced BHR in both non-sensitized and passively sensitized bronchi, (+56.33±8.01% and +99.10±14.52%, respectively; P<0.01 vs. control) and propofol significantly prevented this effect (P>0.05 vs. remifentanil). The inactivation of capsaicin-sensitive sensory nerves via desensitization and blocking NK2 receptor inhibited the BHR remifentanil-induced (P>0.05 vs. controls). The inhibition of iNOS reverted the protective effect of propofol on the BHR induced by remifentanil (non-sensitized: +47.11±7.70%; passively sensitized: +70.51±11.39%; P<0.05 vs. control). Propofol synergistically interacted (overall ≈40%) in preventing the remifentanil-induced BHR. Remifentanil induces BHR via stimulating capsaicin-sensitive sensory nerves that facilitate the cholinergic neurotransmission through the activation of NK2 receptor. The propofol/remifentanil combination may be safely administered in course of TCI-TIVA procedures also in heaves affected horses.


Volumetric analysis of the diagonal band of Broca in patients with schizophrenia and affective disorders: A post-mortem study.
The human diagonal band of Broca is connected to other parts of the limbic system, such as the hippocampus, that are involved in the pathology of schizophrenia. This study aimed to characterize the volume and anterior-to-posterior distance of the human diagonal band of Broca (vertical limb) from post-mortem brains obtained from three groups: healthy control subjects (N = 17), patients with schizophrenia (N = 26), and patients with affective disorders (N = 12). There were no significant differences in the volume or anterior-to-posterior distance in the patients with schizophrenia or affective disorders compared with the healthy control subjects. To date, this is the first post-mortem investigation measuring the volume and the anterior-to-posterior distance of the diagonal band of Broca (vertical limb) in patients with schizophrenia or affective disorders compared with healthy control subjects.


Pharmacokinetics of the acyclovir pro-drug valaciclovir after escalating single- and multiple-dose administration to normal volunteers.
The pharmacokinetics and safety of the L-valyl ester pro-drug of acyclovir, valaciclovir (256U87), were investigated in two phase I, placebo-controlled trials in normal volunteers. These included a single-dose study with doses from 100 to 1000 mg (single cohort) and a multiple-dose investigation with doses from 250 to 2000 mg (five separate cohorts). In each cohort, eight subjects received valaciclovir and four subjects received placebo. Pharmacokinetic findings for valaciclovir and acyclovir were consistent in the two studies. Valaciclovir was rapidly and extensively converted to acyclovir, resulting in significantly greater acyclovir bioavailability (approximately threefold to fivefold) compared with that historically observed with high-dose (800 mg) oral acyclovir. At the higher valaciclovir doses, acyclovir maximum concentration and daily area under the concentration-time curve approximated those obtained with intravenous acyclovir. The favorable safety profile and enhanced acyclovir bioavailability from valaciclovir administration has prompted additional clinical evaluations for zoster and herpes simplex virus treatment, as well as cytomegalovirus suppression in immunocompromised patients.


Visualization of tumors and metastases in live animals with bacteria and vaccinia virus encoding light-emitting proteins.
We have shown that bacteria injected intravenously into live animals entered and replicated in solid tumors and metastases. The tumor-specific amplification process was visualized in real time using luciferase-catalyzed luminescence and green fluorescent protein fluorescence, which revealed the locations of the tumors and metastases. Escherichia coli and three attenuated pathogens (Vibrio cholerae, Salmonella typhimurium, and Listeria monocytogenes) all entered tumors and replicated. Similarly, the cytosolic vaccinia virus also showed tumor-specific replication, as visualized by real-time imaging. These findings indicate that neither auxotrophic mutations, nor vaccinia virus deficient for the thymidine kinase gene, nor anaerobic growth conditions were required for tumor specificity and intratumoral replication. We observed localization of tumors by light-emitting microorganisms in immunocompetent and in immunocompromised rodents with syngeneic and allogeneic tumors. Based on their 'tumor-finding' nature, bacteria and viruses may be designed to carry multiple genes for detection and treatment of cancer.


Structural, vibrational, electronic, NMR and reactivity analyses of 2-amino-4H-chromene-3-carbonitrile (ACC) by ab initio HF and DFT calculations.
This study represents an integrated approach towards understanding the vibrational, electronic, NMR, reactivity and structural aspects of 2-amino-4H-chromene-3-carbonitrile (ACC). A detailed interpretation of the FT IR, UV and NMR spectra were reported. Theoretical calculations were performed by ab initio HF and density functional theory (DFT)/B3LYP method using 6-311++G(d,p) basis sets. The electronic properties was also studied and the most prominent transition corresponds to π→π*. The lower frontier orbital energy gap and high dipole moment illustrates the high reactivity of the title molecule. The NMR results indicated that the observed chemical shifts depend not only on the structure of the molecule being studied, but also on the solvent used. ACC exhibited good nonlinear optical activity and was much greater than that of urea. Molecular electrostatic potential (MEP) results predicted that the enaminonitrile fragment of ACC to be the most reactive site for both electrophilic and nucleophilic attack. In addition, the thermodynamic properties of the compound were calculated at different temperatures and corresponding relations between the properties and temperature were also studied.


Diagnosis of empty sella with CT scan.
The diagnosis of empty sella was made correctly by CT scanning in 100% of 19 cases studied.


A New Editor in Chief for Molecules (It's Been a Fun Ride).
It is with mixed feelings that I put fingers to keyboard to write this, perhaps my last Editorial as Editor-in-Chief of Molecules [...].


Triage assessments and the activation of rapid care protocols for acute stroke patients.
Rapid care protocols developed to reduce in-hospital delay times in the assessment of acute stroke patients are now common in Emergency Departments. Correct triage identification and prioritisation is vital to instigate this process and increase the eligibility of patients for acute stroke treatments. We set out to examine triage assessments of acute stroke patients and investigate factors associated with the instigation of rapid care protocols (allocation of triage category 1 or 2) for acute stroke patients presenting within 2 h of symptom onset. A retrospective assessment of emergency department records was undertaken for stroke patients presenting to three hospitals in Melbourne over six months in 2010. 798 patients were included in the study. Among acute stroke patients who presented within 2 h (n=185), 173 (94%) were identified as stroke at triage with 10 cases identified as "altered conscious state". In all cases not identified as stroke the patient was diagnosed with intracerebral haemorrhage. 132 cases (71%) were allocated a triage category 1 or 2. Facial weakness (p=0.002) and presentation to Monash Medical Centre (p=<0.001), were significantly associated with triage category 1 or 2. Virtually all acute stroke patients were identified at triage, however 30% were not allocated an urgent triage category (1 or 2). Further education strategies may be required to develop awareness of rapid care protocols for acute stroke patients among triage nurses and ensure the uniform application of Acute Stroke Guidelines and local rapid care pathways.


Assembly of motor circuits in the spinal cord: driven to function by genetic and experience-dependent mechanisms.
Motor circuits in the spinal cord integrate information from various sensory and descending pathways to control appropriate motor behavior. Recent work has revealed that target-derived retrograde signaling mechanisms act to influence sequential assembly of motor circuits through combinatorial action of genetic and experience-driven programs. These parallel activities imprint somatotopic information at the level of the spinal cord in precisely interconnected circuits and equip animals with motor circuits capable of reacting to changing demands throughout life.


Spatial resolution of transcranial pulsed Doppler technique in vitro evaluation of the sensitivity distribution of the sample volume.
The spatial resolution of pulsed Doppler sonography is determined by the size of the sample volume. It is known that the axial length is dependent upon the duration of the range gate interval and the lateral extension upon the beam width. In addition, the working size is also a function of the sensitivity distribution within the sample volume. All of these parameters determine the working size of the sample volume. Especially for the transcranial Doppler evaluation of the basal cerebral arteries, the site and the working size of the sample volume are essential diagnostic criteria. To measure the working size of the sample volume a flow rig with a thin tube target has been developed and used. The highest sensitivity (100% level) was registered only in a relatively small area and only if the center of the sample volume hit the target. At the 10% level the size of the sample volume increased 5 to 10 times in the lateral and axial dimension in comparison with the 90% level. Therefore, the Doppler signal from a strong reflector distant from the center of the sample volume may mask the signal of a weak reflector located within the center. This lack of spatial resolution due to sensitivity effects may result in clinical misinterpretation. The manufacturers should be urged to supply more precise information relative to the sample volume size.


Elexacaftor - Tezacaftor - Ivacaftor treatment improves systemic infection parameters and Pseudomonas aeruginosa colonization rate in patients with cystic fibrosis a monocentric observational study.
The CFTR-modulating therapy Elexaftor - Tezacaftor - Ivacaftor (ETI) has been widely prescribed since its approval in 2020 in the European Union. The aim of this study was to methodically evaluate the effects of an ETI treatment on clinical, biochemical data and Pseudomonas colonization in order to demonstrate its efficacy. This prospective monocentric study comprised 69 patients diagnosed with cystic fibrosis aged at least 12 years and treated with ETI between September 2020 and November 2021. Clinical and laboratory data of each patient and study visit were collected before and after 24 weeks of ETI treatment. Follow-up status of Pseudomonas aeruginosa (PsA) colonization was assessed after one year of therapy by regularly determined sputum or throat swab samples. Marked improvements biochemical markers of systemic inflammation as white blood cell count, levels of immunoglobulins A, G and M and albumin within 24 weeks of therapy were observed. ETI treatment proved to be effective as seen by amelioration of lung function and sweat chloride concentration. Assessment of PsA colonization status revealed a conversion from a positive to negative detection in 36% of the cases after one year of therapy. ETI treatment effectively improves systemic inflammation parameters and shows promising results in PsA status conversion.


QT Variability Index is Correlated with Autonomic Nerve Activity in Healthy Children.
The QT variability index (QTVI), which measures the instability of myocardial repolarization, is usually calculated from a single electrocardiogram (ECG) recording and can be easily applied in children. It is well known that frequency analysis of heart rate variability (HRV) can detect autonomic balance, but it is not clear whether QTVI is correlated with autonomic tone. Therefore, we evaluated the association between QTVI and HRV to elucidate whether QTVI is correlated with autonomic nerve activity. Apparently, healthy 320 children aged 0-7 years who visited Fujita Health University Hospital for heart checkup examinations were included. The RR and QT intervals of 60 continuous heart beats were measured, and the QTVI was calculated using the formula of Berger et al. Frequency analysis of HRV, including the QTVI analysis region, was conducted for 2 min and the ratio of low-frequency (LF) components to high-frequency (HF) components (LF/HF) and HF/(LF + HF) ratio was calculated as indicators of autonomic nerve activity. Then, the correlations between QTVI and these parameters were assessed. QTVI showed a significant positive correlation with LF/HF ratio (r = 0.45, p < 0.001) and negative correlation with HF/(LF + HF) ratio (r = -0.429, p < 0.001). These correlations remained after adjustment for sex and age. QTVI, which is calculated from non-invasive ECG and can detect abnormal myocardial repolarization, is significantly correlated with frequency analysis of HRV parameters. QTVI reflects autonomic nerve balance in children.


Aquatic vision and the modulation transfer properties of unlighted and diffusely lighted natural waters.
The modulation transfer function (MTF) of well-mixed unlighted and diffusely lighted samples of clear natural waters for path lengths up to 4 m was measured. The measuring conditions simulated the situation for horizontal aquatic vision. In unlighted water, the MTF decreased relatively slowly with increasing path length and spatial frequency up to 150 c/deg. We interpret this as the result of low-angle forward scattering of light from the target. For diffusely lighted water, the MTF fell much more rapidly with path length, but was nearly independent of spatial frequency. Here, scattering of ambient light into the light path contributes an additional veiling glare or path radiance, which is independent of spatial frequency but degrades the MTF strongly with increasing path length. These scattering processes are independent of wavelength in the visible spectrum. The modulation transfer properties of these waters do not preclude high aquatic visual acuity. However, the useful range of high acuity vision in diffusely lighted water is much less than for unlighted water. This places special requirements upon the design of high-acuity aquatic eyes.


Variation in stratum corneum protein content as a function of anatomical site and ethnic group.
Quantification of stratum corneum (SC) protein levels from tape strippings is frequently used to investigate skin conditions, to correct for amounts of SC protein removed in SC biomarker studies and to determine distribution of topically applied ingredients. In recent years, a rapid and convenient method for SC protein quantification from tape strippings has become available using infrared densitometry (IRD). However, standard curves have only been generated for Caucasian forearm and shoulder SC and have been assumed to be correct not only for facial SC but also for SC samples of other ethnic groups. The aim of this study was to investigate whether the use of IRD for SC protein measurement is valid for other body sites such as the cheek and for measuring SC protein content of darkly pigmented skin types. Ten Caucasian and ten Black African female subjects with self-assessed normal skin participated in the study. Tape strippings were collected from two different body sites (forearm and cheek). First from the tape strippings, the SC optical absorption was determined densitometrically. This obtained absorption (%) was compared with absolute SC protein extracted from the same tapes using a colorimetric microbicinchoninic acid (μBCA) assay. Higher amounts of SC protein were removed from the forearm compared with the cheek (P < 0.01). The absolute SC protein concentration quantified by μBCA assay and the absorption of SC proteins by IRD followed a similar profile. There was no significant difference found between the two ethnicities in SC protein (P > 0.05). The overall coefficient of determination (R(2) ) shows a good fit to the regression line between the two methods in both sites (forearm = 0.82, cheek = 0.77). Also, both ethnicities showed good correlation (R(2) ≥ 0.69, P = 0.01). Facial SC is morphologically distinct from the forearm, as demonstrated by the differences in amounts of SC removed. Although the data distribution in different subject groups varied, the regression was always quite similar between the two body sites and both ethnic groups. Also, the correlations were similar to previously published data on other body sites. The resultant calibration curves can be used as a rapid indirect protein assessment of tape strippings from the cheek.


Vaginal delivery after 3 previous caesarean sections.
A patient who had had 3 previous Caesarean sections was permitted a trial of scar in her subsequent confinement. Labour occurred spontaneously at 39 weeks, and was closely monitored. After an uneventful labour of 3 1/2 hours, a Wrigley forceps lift-out was performed. There was no maternal or neonatal morbidity and the uterine scar was intact.


Comparison of different methods of functional evaluation in patients with chronic heart failure.
Stratification of the severity of heart failure has major prognostic and therapeutic implications. To prospectively compare different methods of assessment of functional capacity in patients with chronic heart failure (CHF). We studied 143 patients (78 male and 65 female) with CHF aged less than 70 years (mean 57.3 years). Functional assessment was made clinically according to NYHA classification and according to the Goldman Activity Scale Classification (GASC). Cardiovascular performance was measured by peak O(2) consumption (pVO(2)) and anaerobic threshold (AT) at cardiopulmonary exercise test and by the distance walked during a 6-min walk test (6-MWT). Clinical scales resulted significantly related. Peak VO(2) and AT showed a mild relation with distance covered at 6-MWT (r=0.56 and r=0.46, respectively). Concordance between NYHA classification and levels of performance at cardiopulmonary exercise test or at 6-MWT was less than 50%. Our results suggest that none of the usually employed methods give a definitive assessment of functional capacity of cardiovascular system and a high degree of discordance exists among the results of different tests in the same patient. Although NYHA classification maintains its value in clinical evaluation of patients with CHF, the 6-min walk test is recommended in patients with mild-to-moderate CHF (II-III NYHA classes) as a simple and useful screening test to select patients for further diagnostic evaluation.


Comparative effects of palm vitamin E and alpha-tocopherol on healing and wound tissue antioxidant enzyme levels in diabetic rats.
The effect of supplementing 200 mg/kg body weight palm vitamin E (PVE) and 200 mg/kg body weight alpha-tocopherol (alpha-Toc) on the healing of wounds in streptozotocin-induced diabetic rats was evaluated. The antioxidant potencies of these two preparations of vitamin E were also evaluated by determining the antioxidant enzyme activities, namely, glutathione peroxidase (GPx) and superoxide dismutase (SOD), and malondialdehyde (MDA) levels in the healing of dermal wounds. Healing was evaluated by measuring wound contractions and protein contents in the healing wounds. Cellular redistribution and collagen deposition were assessed morphologically using cross-sections of paraffin-embedded day-10 wounds stained according to the Van Gieson method. GPx and SOD activities as well as MDA levels were determined in homogenates of day-10 dermal wounds. Results showed that PVE had a greater potency to enhance wound repair and induce the increase in free radical-scavenging enzyme activities than alpha-Toc. Both PVE and alpha-Toc, however, were potent antioxidants and significantly reduced the lipid peroxidation levels in the wounds as measured by the reduction in MDA levels.


Serological responses of sheep and cattle exposed to natural Toxoplasma infection.
During a four and a half year period a group of cattle was grazed continuously with a group of sheep and observed for Toxoplasma antibodies. Initially, there were 25 cattle and 31 sheep, but these were reduced to 19 and 18, respectively, by the end of the observation. Only transient antibody responses were noted in 2 cattle, whereas persistent titres developed in 12 sheep. Interpreted in the light of available information, these results were taken to indicate that cattle do not readily acquire persistent T. gondii infections.


DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells.
Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or "reperfusion" of renal proximal tubular cells (RPTCs) after ATP depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death.


A systematic review of overweight and obesity as risk factors and targets for clinical intervention for urinary incontinence in women.
To review the epidemiological literature of urinary incontinence with respect to overweight and obesity as a risk factor, and how the findings eventually fulfill general criteria for being a causal factor for the condition. Likewise to review all interventional studies assessing the effect of weight reduction on incontinence. Systematic searches until June 2008 for publications of community based prevalence studies with bivariate or multivariate analyses of the association between urinary incontinence in women and overweigh/obesity. In addition an attempt was made to identity and assess all relevant longitudinal studies, prospective case series, and trials, whatever design. There is evidence 3 and some evidence 2 level data to support that in addition to BMI, waist-hip ratio and thus abdominal obesity may be an independent risk factor for incontinence in women. Only a few interventional studies have been carried out to assess the effect of weight reduction on incontinence. Five studies report effect on incontinence after surgical weight reduction procedures, and one study after a weight reduction program, thus giving some level 2 documentation. There are three RCTs which all show reducing incontinence by weight loss (level of evidence 1). Epidemiological studies document overweight and obesity as an important risk factor for urinary incontinence. There is now valid documentation for weight reduction as a treatment for urinary incontinence in women.


Investigation into isomerization reaction of phenylalanine aminomutase from Pantoea agglomerans.
Phenylalanine aminomutase (PaPAM) from Pantoea agglomerans is a member of the MIO (4-methylene-imidazol-5-one) family of enzymes, which isomerizes α-phenylalanine to β-phenylalanine, and could be used to synthesize unnatural β-arylalanine. However, the mechanism of isomerization reaction is not clear. To investigate the mechanism, the gene (pam), which encodes PaPAM, was first expressed in E.coli, and recombinant PaPAM was prepared using affinity chromatography. Then, 15N-(2S)-α-phenylalanine, (2S)-(3-2H2)-α-phenylalanine and (2S,3S)-[2,3-2H2]-α-phenylalanine were used as substrates to analyze the mechanism of isomerization reaction. The results of MS and NMR showed that the isomerization reaction was performed through the intramolecular exchange of NH2 with pro-3R hydrogen of α-phenylalanine. The PaPAM shuttles the α-NH2 of α-phenylalanine to β site to replace the pro-3R hydrogen. Simultaneously, the pro-3R hydrogen is shifted to α site to produce β-phenylalanine. Furthermore, a key residue, Phe at position 455 in the active site, was determined to control the exchange way using molecular docking and sequence alignment of MIO family enzymes. The results indicated that the key 455 Phe residue is involved in changing the binding orientation of the carboxyl group of the intermediate trans-cinnamic acid to control the NH2-H pair exchange.


Roux-en-Y-Bariatric Surgery Reduces Markers of Metabolic Syndrome in Morbidly Obese Patients.
Obesity is closely linked to increased markers of metabolic syndrome and development of diabetes. Roux-en-Y bariatric surgery reduces hyperinsulinemia and improves insulin sensitivity and hence benefits morbidly obese patients. To determine changes in markers of metabolic syndrome, pancreatic function, and hepatic insulin sensitivity in patients before and 1 year after undergoing Roux-en-Y gastric bypass surgery. We enrolled 43 consecutive patients in a single center. Markers for metabolic syndrome included proinsulin, insulin, C-peptide, liver enzymes, and serum levels of selected microRNAs hsa-miR-122, hsa-miR-130, hsa-miR-132, and hsa-miR-375. After surgery, all patients showed a significant 37% drop of body mass index (p < 0.001). Furthermore, proinsulin (59% reduction, p < 0.001), insulin (76% reduction, p < 0.001), and C-peptide (56% reduction, p < 0.001) were all reduced 1 year after surgery. Using the hepatic insulin clearance score, we determined a significant increase in hepatic insulin clearance after surgery (76% increase, p < 0.001). Especially diabetic patients showed a marked 2.1-fold increase after surgery. Hepatic enzymes ALT (35% reduction, p = 0.002) and γGT (48% reduction, p < 0.001) were significantly reduced in all patients with similar improvement in diabetic and non-diabetic patients. miRNAs hsa-miR-122, hsa-miR-130, and hsa-miR-132 were all significantly reduced whereas hsa-miR-375 was increased after gastric bypass surgery (p < 0.001 for all miRNAs). Both liver and pancreatic stress parameters were reduced significantly 1 year after Roux-en-Y gastric bypass surgery suggesting an overall amelioration of the metabolic syndrome in all patients regardless of previous health status.


MR imaging differentiation of Fe2+ and Fe3+ based on relaxation and magnetic susceptibility properties.
The aim of this study is to evaluate the MR imaging behavior of ferrous (Fe2+) and ferric (Fe3+) iron ions in order to develop a noninvasive technique to quantitatively differentiate between both forms of iron. MRI was performed at 3 T in a phantom consisting of 21 samples with different concentrations of ferrous and ferric chloride solutions (between 0 and 10 mmol/L). A multi-echo spoiled gradient-echo pulse sequence with eight echoes was used for both T 2* and quantitative susceptibility measurements. The transverse relaxation rate, R 2* = 1/T 2*, was determined by nonlinear exponential fitting based on the mean signals in each sample. The susceptibilities, χ, of the samples were calculated after phase unwrapping and background field removal by fitting the spatial convolution of a unit dipole response to the measured internal field map. Relaxation rate changes, ΔR 2*(c Fe), and susceptibility changes, Δχ(c Fe), their linear slopes, as well as the ratios ΔR 2*(c Fe) / Δχ(c Fe) were determined for all concentrations. The linear slopes of the relaxation rate were (12.5 ± 0.4) s-1/(mmol/L) for Fe3+ and (0.77 ± 0.09) s-1/(mmol/L) for Fe2+ (significantly different, z test P < 0.0001). The linear slopes of the susceptibility were (0.088 ± 0.003) ppm/(mmol/L) for Fe3+ and (0.079 ± 0.006) ppm/(mmol/L) for Fe2+. The individual ratios ΔR 2*/Δχ were greater than 40 s-1/ppm for all samples with ferric solution and lower than 20 s-1/ppm for all but one of the samples with ferrous solution. Ferrous and ferric iron ions show significantly different relaxation behaviors in MRI but similar susceptibility patterns. These properties can be used to differentiate ferrous and ferric samples.


Phospholipase A(2) Activity in Gingival Crevicular Fluid from Patients with Periodontal Disease: A possible Marker of Disease Activity.
The activity of phospholipase A(2) in human gingival crevicular fluid (GCF) associated with periodontal disease was demonstrated. Based upon the presence or absence of bleeding on probing (BOP), which is a marker for the disease activity, there were higher levels of the enzyme activity in BOP positive, than in negative sites. When the BOP positive sites became negative after periodontal therapy, the enzyme activity decreased dramatically to almost undetectable levels. There were no significant differences between the activity before and after treatment when the BOP positive sites remained unchanged. These results suggest that the activity in GCF reflects periodontal disease conditions and that it can be used as a marker for disease activity.


Recombineering using RecET-like recombinases from Xenorhabdus and its application in mining of natural products.
Xenorhabdus can produce a large number of secondary metabolites with insecticidal, bacteriostatic, and antitumor activities. Efficient gene editing tools will undoubtedly facilitate the functional genomics research and bioprospecting in Xenorhabdus. In this study, BlastP analysis using the amino acid sequences of Redαβ or RecET recombinases as queries resulted in the identification of an operon (XBJ1_operon 0213) containing RecET-like recombinases encoding genes from the genome of Xenorhabdus bovienii strain SS-2004. Three proteins encoded by this operon was indispensable for full activity of recombineering, namely XBJ1-1173 (RecE-like protein), XBJ1-1172 (RecT-like protein), and XBJ1-1171 (single-strand annealing protein). Using this newly developed recombineering system, a gene cluster responsible for biosynthesis of a novel secondary metabolite (Min16) was identified from X. stockiae HN_xs01 strain. Min16 which exhibited antibacterial and cytotoxic activities was determined to be a cyclopeptide composed of Acyl-Phe-Thr-Phe-Pro-Pro-Leu-Val by using high-resolution mass spectrometry and nuclear magnetic resonance analysis, and was designated as changshamycin. This host-specific recombineering system was proven to be effective for gene editing in Xenorhabdus, allowing for efficient discovery of novel natural products with attractive bioactivities. KEY POINTS: • Screening and identification of efficient gene editing tools from Xenorhabdus • Optimization of the Xenorhabdus electroporation parameters • Discovery of a novel cyclopeptide compound with multiple biological activities.


Interval hypoxic training.
Interval hypoxic training (IHT) is a technique developed in the former Soviet Union, that consists of repeated exposures to 5-7 minutes of steady or progressive hypoxia, interrupted by equal periods of recovery. It has been proposed for training in sports, to acclimatize to high altitude, and to treat a variety of clinical conditions, spanning from coronary heart disease to Cesarean delivery. Some of these results may originate by the different effects of continuous vs. intermittent hypoxia (IH), which can be obtained by manipulating the repetition rate, the duration and the intensity of the hypoxic stimulus. The present article will attempt to examine some of the effects of IH, and, whenever possible, compare them to those of typical IHT. IH can modify oxygen transport and energy utilization, alter respiratory and blood pressure control mechanisms, induce permanent modifications in the cardiovascular system. IHT increases the hypoxic ventilatory response, increase red blood cell count and increase aerobic capacity. Some of these effects might be potentially beneficial in specific physiologic or pathologic conditions. At this stage, this technique appears interesting for its possible applications, but still largely to be explored for its mechanisms, potentials and limitations.


Ultrastructure and cytochemistry of the yolk syncytial layer in the alevin of trout (Salmo fario trutta L. and Salmo gairdneri R.) after hatching. II. The cytoplasmic zone.
In contrast to the vitellolysis zone which is involved in the degradation of the yolk, the cytoplasmic zone of the yolk syncytial layer, composed of many cytoplasmic organelles, is implicated in a secretory process. The granular endoplasmic reticulum of the latter is extremely well developed and organized into trabeculae. The yolk nuclei show a RNA positive reaction. The Golgi apparatus is implicated in the elaboration of very low density lipoproteins (VLDL) and of acid phosphatase. The numerous mitochondria seem to suggest an important energy metabolism in the solubilisation area. The appearance of certain special structures (crystalline bodies, pseudovesicular structures, lipochondria) as well as their relation with the organelles of the cytoplasmic zone, re-inforces the impression of a layer with a secretory nature and suggests its participation in the remodelling of the yolk products produced in the vitellolysis zone. The results of the investigations concerning the acid phosphatase activity suggest that this enzyme plays a role on the one hand in the degradation of certain platelets which penetrate into the cytoplasmic zone, and on the other hand in the regulation of VLDL, in the lysis of secretory products elaborated by the cytoplasmic zone. The possible presence of microperoxisomes is discussed as well as the positive detection of glucose-6-phosphate dehydrogenase.


Binding of [3H]triamcinolone acetonide-receptor complexes to chromatin from the B-cell leukemia line, BCL1.
The binding characteristics of partially purified glucocorticoid receptor complexes from hormone sensitive, non-differentiating BCL1 cells to sequentially deproteinized BCL1 chromatin-cellulose was investigated. [3H]Triamcinolone acetonide (TA)-receptor complexes were purified (approx. 30-fold) from DEAE-cellulose columns by salt elution which allowed receptor activation only in the absence of molybdate. Addition of 10 mM molybdate completely blocked salt activation. The binding pattern of the activated [3H]TA-receptor complexes to chromatin-cellulose extracted with 0-8 M guanidine hydrochloride revealed three regions of increased binding activity (acceptor sites), at 2, 5 and 7 M guanidine hydrochloride. Acceptor site binding was markedly reduced for chromatin extracted with 3, 6 and 8 M guanidine hydrochloride. Non-activated receptor complexes demonstrated very low binding to deproteinized chromatin. It was also shown that chromatin binding required glucocorticoid receptors and that free ligand or ligand bound to other proteins did not bind significantly to chromatin. In addition, binding of [3H]TA-receptor complexes to partially deproteinized chromatin was competable by unlabeled TA-receptor complexes. Scatchard analysis demonstrated that chromatin from non-differentiating BCL1 cells possesses multiple, high-affinity binding sites which differ in their affinity for the glucocorticoid receptor. Partially deproteinized chromatin from lipopolysaccharide-stimulated BCL1 cells demonstrated a different pattern of receptor binding, i.e., receptor binding was significantly greater to chromatin previously extracted with 6-8 M guanidine hydrochloride. These results suggest that differentiation alters the state of chromatin and the interaction of non-histone protein/DNA acceptor sites with glucocorticoid receptors. These alterations may play a role in the acquisition of hormone resistance.


Optimizing waiting duration for renal transplants in the setting of renal malignancy: is 2 years too long to wait?
For potential transplant recipients with a prior history of renal malignancy, no evidence-based recommendations currently exist with regard to waiting duration on dialysis. We aim to improve decision making by evaluating the impact of waiting duration on the outcomes of kidney cancer patients awaiting renal transplantation. The United States Renal Data System was used to identify patients with a known cause of end-stage renal disease (ESRD) from 1983 to 2007. Evaluation of overall survival (OS) was performed with Kaplan-Meier estimates and Cox proportional hazards models. Fine-Gray competing risk models were used to assess cancer-specific mortality (CSM) and non-cancer-specific mortality (NCSM). Of 1 374 175 patients with ESRD, 228 984 (16.7%) received transplantation. Transplant recipients with renal malignancy-associated ESRD (RM-ESRD) had longer waiting durations than those with other known causes of ESRD (2.4 versus 1.3 years; P < 0.0001). RM-ESRD patients who had shorter waiting durations (0-2 years) had better OS than those who waited longer (2+ years) (10-year OS 69.0 versus 46.7%, respectively; P < 0.0001), with similar CSM (10-year CSM 10.3 versus 10.2%, respectively; P = 0.883), whereas NCSM was worse for those with longer waiting durations (10-year NCSM 20.7 versus 44.3%, respectively; P < 0.0001). On Cox modeling, the status of RM-ESRD was not a significant predictor (P = 0.07), while longer waiting duration remained significant (P < 0.0001). We found that CSM was not affected by waiting duration, while NCSM significantly improved with shorter wait times. These findings suggest that the OS of potential transplant recipients with RM-ESRD may be improved by reducing waiting duration.


Fulminant transfusion-associated graft-versus-host disease in a premature infant.
A fatal case of transfusion-associated graft-versus-host disease developed in a premature infant after receiving several blood products, including nonirradiated white blood cells. Transfusion-associated graft-versus-host disease can be prevented. Irradiation of blood products is the least controversial and most effective method. Treatment was unsuccessful in most reported cases of transfusion-associated graft-versus-host disease. Therefore irradiation of blood products before transfusing to patients susceptible to transfusion-associated graft-versus-host disease is strongly recommended.


On the ancient nature of introns.
We discuss some of the arguments for introns arising early or late in evolution. We outline the exon theory of genes and discuss the series of discoveries of introns in the gene (TPI) encoding triosephosphate isomerase (TPI) that have filled out a series of better fits to the Go plot, culminating in the 1986 prediction of an intron position that was finally discovered in 1992. We present a statistical argument that the 11-intron structure of TPI (based on attributing all of the introns to an ancestral gene and interpreting three cases of very close intron positions as examples of sliding) has a clear relationship to the protein structure. The exons of this 11-intron TPI are a better approximation to Mitiko Go's modules (Go, 1981) than are 99.9% of all alternative exon patterns corresponding to 11 introns placed randomly in the gene, and better than 96% of all alternative patterns in which the lengths of the exons are preserved while the introns are moved. We combine four tests relating exons to protein structure: (i) whether the exons are compact modules, (ii) whether the exons contain most of the close contacts in the protein, (iii) whether the exon configuration maximized buried surface area along the backbone, and (iv) whether the exons maximize their content of hydrogen bonds. On a joint measure for these tests, the native exon structure with 11 introns fits these tests better than 99.4% of all alternative structures obtained by permuting the exon lengths and intron positions.(ABSTRACT TRUNCATED AT 250 WORDS)


Differential Outcomes of Adolescents with Chronically Ill and Healthy Parents.
Approximately 10% of children grow up with a parent who has been diagnosed with a chronic medical condition (CMC) and seem to be at risk for adjustment difficulties. We examined differences in behavioral, psychosocial and academic outcomes between 161 adolescents from 101 families with a chronically ill parent and 112 adolescents from 68 families with healthy parents, accounting for statistical dependence within siblings. Children between 10 and 20 years and their parents were visited at home and filled in questionnaires. Multilevel analyses showed that 20-60% of the variance in most adolescent outcomes was due to the family cluster effect, especially in internalizing problem behavior, caregiving variables and quality of parent attachment. Conversely, the variance in stress and coping variables and grade point average (GPA) was mainly due to individual characteristics. Adolescents with parents affected by CMC displayed more internalizing problems than the comparison group and scored higher on frequency of household chores, caregiving responsibilities, activity restrictions, isolation, daily hassles and stress. In addition, their grade point average was comparatively worse. No group differences in externalizing problems, coping skills and quality of parent attachment were found. In conclusion, the family cluster effect largely explains adolescent outcomes and should be accounted for. Adolescents with parents affected by CMC are subject to an increased risk for internalizing problems, adverse caregiving characteristics, daily hassles, stress and a low GPA. According to a family-centered approach, school counselors and health care practitioners should be alert to adjustment difficulties of children with a chronically ill parent.


A New Era of Diagnosis and Therapy in Acute Aortic Syndromes: The Mainz-Essen Experience (Part II)-Management and Outcomes.
Over the years, the cardiovascular department of Johannes Gutenberg University in Mainz-West-German Heart Centre in Essen (Germany) designed and implemented the hybrid operating room (2003) along with advanced endovascular and surgical procedures, including the frozen elephant trunk technique. For the study purpose, the Mainz-Essen experience on acute aortic syndromes was summarized by considering original articles from single-center or multicenter studies performed at West German Heart Centre, Essen, Germany, or at the cardiovascular department of Johannes Gutenberg University, Mainz, Germany. We present the 35-year-long Mainz-Essen research, education, and patient management journey in creating an integrated multidisciplinary "Aortic Center" in the heart of Europe.


Effects of infection prevention and control measures on patient and visitor violence against health workers in China during COVID-19 pandemic.
To examine trends in patient and visitor violence (PVV) among large public hospitals from 2016 to 2020 in China, and investigate the effects of infection prevention and control (IPC) measures on PVV during the COVID-19 pandemic. The hospital-level data of PVV used in this study from 2016 to 2020 in three cities in northern China were extracted from the database of the Medical Quality and Safety Notification System from 41 public hospitals. The difference-in-difference (DID) method was used to estimate the effects of IPC measures on PVV. The empirical strategy was to compare changes in the incidence rate of PVV in public hospitals where IPC measures were stricter to relatively weaker hospitals. From 2019 to 2020, the incidence rate of PVV decreases from 4.59 to 2.15% for high-IPC measure level hospitals and increases from 4.42 to 4.56% for medium-IPC measure level hospitals. The results from the DID models showed that as the IPC measure level increased, the incidence rate of PVV (β = -3.12, 95% CI = -5.74 ~ -0.50) decreased more significantly based on controlling for hospital fixed effects and time trends. The multi-dimensional and comprehensive IPC measures throughout the pandemic in China have not only controlled the pandemic, but also directly or indirectly reduced the incidence rate of PVV by alleviating the stress of health workers and the crowded working environment, creating a good order of admission, and reducing patient waiting time.


Expression of Wnt and NCX1 and its correlation with cardiomyocyte apoptosis in mouse with myocardial hypertrophy.
To study the correlation between expression of Wnt and NCX1 and cardiomyocyte apoptosis in mouse with myocardial hypertrophy. C57B/16 male mice were given the subcutaneous injection of 1 mg/kg isoprenaline to build the myocardial hypertrophy model. After 14 d of model building, mice were executed by cervical vertebra luxation. The ratio of heart weight/body weight (HW/BW) and heart weight/tibia length (HW/TL) was observed and proved using HE staining that detected the size of cardiomyocytes. 40 male C57B/16 mice were randomly divided into the sham group (normal saline) and model group (isoprenaline), with 20 mice in each group. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling was applied to detect the cardiomyocyte apoptosis; while Western blot and immunohistochemistry were employed to detect the expression of Wnt and NCX1. Meanwhile, the correlation between these two proteins and cardiomyocyte apoptosis was explored. Compared with the sham group, the ratio of HW/BW and HW/TL was increased in the model group, as well as the bigger and hypertrophied cardiomyocytes, decreased number and increased apoptosis of cardiomyocytes, and increased positive expression of Wnt3a, Wnt5a and NCX1 in the cardiac muscle tissue. Besides, there was positive correlation between the expression of Wnt and NCX1 and the cardiomyocyte apoptosis. The expression of Wnt3a, Wnt5a and NCX1 in mouse with myocardial hypertrophy is increased and positively correlated with the cardiomyocyte apoptosis.


Direct and indirect photodynamic therapy effects on the cellular and molecular components of the tumor microenvironment.
Photodynamic therapy (PDT) is a novel cancer treatment. It involves the activation of a photosensitizer (PS) with light of specific wavelength, which interacts with molecular oxygen to generate singlet oxygen and other reactive oxygen species (ROS) that lead to tumor cell death. When a tumor is treated with PDT, in addition to affect cancer cells, the extracellular matrix and the other cellular components of the microenvironment are altered and finally this had effects on the tumor cells survival. Furthermore, the heterogeneity in the availability of nutrients and oxygen in the different regions of a tridimensional tumor has a strong impact on the sensitivity of cells to PDT. In this review, we summarize how PDT affects indirectly to the tumor cells, by the alterations on the extracellular matrix, the cell adhesion and the effects over the immune response. Also, we describe direct PDT effects on cancer cells, considering the intratumoral role that autophagy mediated by hypoxia-inducible factor 1 (HIF-1) has on the efficiency of the treatment.


Immediate effects of modified landing pattern on a probabilistic tibial stress fracture model in runners.
Tibial stress fracture is a common injury in runners. This condition has been associated with increased impact loading. Since vertical loading rates are related to the landing pattern, many heelstrike runners attempt to modify their footfalls for a lower risk of tibial stress fracture. Such effect of modified landing pattern remains unknown. This study examined the immediate effects of landing pattern modification on the probability of tibial stress fracture. Fourteen experienced heelstrike runners ran on an instrumented treadmill and they were given augmented feedback for landing pattern switch. We measured their running kinematics and kinetics during different landing patterns. Ankle joint contact force and peak tibial strains were estimated using computational models. We used an established mathematical model to determine the effect of landing pattern on stress fracture probability. Heelstrike runners experienced greater impact loading immediately after landing pattern switch (P<0.004). There was an increase in the longitudinal ankle joint contact force when they landed with forefoot (P=0.003). However, there was no significant difference in both peak tibial strains and the risk of tibial stress fracture in runners with different landing patterns (P>0.986). Immediate transitioning of the landing pattern in heelstrike runners may not offer timely protection against tibial stress fracture, despite a reduction of impact loading. Long-term effects of landing pattern switch remains unknown.


[A method for covering defects of the lip].
Numerous methods have been described to reconstruct lower lip defects. A further method is presented which is suitable for lateral defects of the lower lip and employs a transposition flap similar to Goldstein's method.


Spinal projection to the dorsolateral nucleus of the caudal basilar pons in the cat.
In the cat, a spinal projection to a restricted area of the basilar pontine grey has been revealed with use of anterograde degeneration technique (Fink-Heimer). The area was ipsilateral to the spinal lesion, restricted to the far caudal limit of the pons, and included the dorsal and the dorsolateral subdivisions of the pontine nuclei (PN). Comparisons following high cervical, midthoracic and upper lumbar spinal lesions did not reveal any somatotopic organization. Only a few spinopontine fibers had origins below segmental level L4. Lesions of various quadrants of the cord indicated that the spinopontine fibers ascended through the dorsolateral funiculus, and not through either the dorsal or the ventral funiculi. Comparison with the degeneration effects of cerebral cortical lesions showed that the spinal projection to the PN overlapped to some extent with the projection from the first sensorimotor and second somatosensory cortices. In the rat no comparable spinopontine projection was found. It is suggested that the spinopontine pathway might forward information to the cerebellum from visceral sensory receptors or perhaps from pools of spinal interneurons.


Manganese(III)-catalyzed facile direct hydroperoxidation of some heterocyclic 1,3-dicarbonyl compounds.
[reaction: see text] The aerobic oxidation of 4-monosubstituted 1,2-diphenylpyrazolidine-3,5-diones 1 was carried out in the presence of a catalytic amount of manganese(III) acetate to quantitatively give the corresponding 4-hydroperoxypyrazolidinediones 2. A similar autoxidation of the 5-monosubstituted barbituric acids 5 and 3-butyl-4-hydroxy-2-quinolinone 7 also gave the corresponding hydroperoxides 5 and 8, respectively, in moderate to excellent yields.


Highly ordered laser imprinted plasmonic metasurfaces for polarization sensitive perfect absorption.
We present polarization-sensitive gap surface plasmon metasurfaces fabricated with direct material processing using pulsed laser light, an alternative and versatile approach. In particular we imprint laser induced periodic surface structures on nanometer-thick Ni films, which are back-plated by a grounded dielectric layer with TiO2 and ZnO deposition followed by Au evaporation. The procedure results in a metal-insulator-metal type plasmonic metasurface with a corrugated top layer consisting of highly-ordered, sinusoidal shaped, periodic, thin, metallic nanowires. The metasurface sustains sharp, resonant gap surface plasmons and provides various opportunities for polarization control in reflection, which is here switched by the size and infiltrating material of the insulating cavity. The polarization control is associated with the polarization sensitive perfect absorption and leads to high extinction ratios in the near-IR and mid-IR spectral areas. Corresponding Fourier-transform infrared spectroscopy measurements experimentally demonstrate that the fabrication approach produces metasurfaces with very well-defined, controllable, sharp resonances and polarization sensitive resonant absorption response which, depending on the insulating cavity size, impacts either the normal or the parallel to the nanowires polarization.


Two-dimensional crystal structures of protein kinase C-delta, its regulatory domain, and the enzyme complexed with myelin basic protein.
Two-dimensional crystals of protein kinase C (PKC) delta, its regulatory domain (RDdelta), and the enzyme complexed with the substrate myelin basic protein have been grown on lipid monolayers composed of phosphatidylcholine: phosphatidylserine: diolein (45:50:5, molar ratio). Images have been reconstructed to 10-A resolution. The unit cells of all three proteins have cell edges a = b and interedge angle gamma = 60 degrees. RDdelta has an edge length of 33 +/- 1 A, and its reconstruction is donut shaped. The three-dimensional reconstructions from the PKCdelta C1b crystal structure () can be accommodated in this two-dimensional projection. Intact PKCdelta has an edge length of 46 +/- 1 A in the presence or absence of a nonhydrolyzable ATP analog, AMP-PnP. Its reconstruction has a similar donut shape, which can accommodate the C1b domain, but the spacing between donuts is greater than that in RDdelta; some additional structure is visible between the donuts. The complex of PKCdelta and myelin basic protein, with or without AMP-PnP, has an edge length of 43 +/- 1 A and a distinct structure. These results indicate that the C1 domains of RDdelta are tightly packed in the plane of the membrane in the two-dimensional crystals, that there is a single molecule of PKCdelta in the unit cell, and that its interaction with myelin basic protein induces a shift in conformation and/or packing of the enzyme.


[Breast implants and anaplastic large cell lymphoma: What do we know?].
There is a new concern about a possible association between anaplastic large cell lymphoma (ALCL) and breast implants. The purpose of this review was to identify and analyze all reported cases of ALCL occurring in patients with breast implants. Therefore, we reviewed all articles published concerning this subject between 1991 and 2011. We found 41 cases of ALCL. The mean age of the patients was 51 years old with an average of 108 months between the implantation and the diagnosis. Over 60 % of the reported cases were aesthetic augmentations. However, none of the published study managed to highlight a correlation between the prosthesis and this lymphoma. Therefore, we believe that for the moment, we can reassure our patients, but we must be aware of this association if a late seroma or a tumefaction occur on prosthesis. The surgical management seems to be essential for the diagnosis and the treatment, especially by the negative ALK and CD 30 expression of this lymphoma.


A keratin/chitosan sponge with excellent hemostatic performance for uncontrolled bleeding.
Uncontrolled bleeding leads to a higher fatality rate in the situation of surgery, traffic accidents and warfare. Traditional hemostatic materials such as bandages are not ideal for uncontrolled or incompressible bleeding. Therefore, it is of great significance to develop a new medical biomaterial with excellent rapid hemostatic effect. Keratin is a natural, biocompatible and biodegradable protein which contains amino acid sequences that induce cell adhesion. As a potential biomedical material, keratin has been developed and paid attention in tissue engineering fields such as promoting wound healing and nerve repair. Herein, a keratin/chitosan (K/C) sponge was prepared to achieve rapid hemostasis. The characterizations of K/C sponge were investigated, including SEM, TGA, liquid absorption and porosity, showing that the high porosity up to 90.12 ± 2.17 % resulted in an excellent blood absorption. The cytotoxicity test and implantation experiment proved that the K/C sponge was biocompatible and biodegradable. Moreover, the prepared K/C sponge showed better hemostatic performance than chitosan sponge (CS) and the commercially available gelatin sponge in both rat tail amputation and liver trauma bleeding models. Further experiments showed that K/C sponge plays a hemostatic role through the endogenous coagulation pathway, thus shortening the activated partial thromboplastin time (APTT) effectively. Therefore, this study provided a K/C sponge which can be served as a promising biomedical hemostatic material.


The influence of clinical factors on human stimulated parotid flow rate in cancer and other patients.
Reduced salivary secretion can produce a wide variety of complaints, having a negative impact on the daily life of a patient. Multiple causes of salivary hypofunction are described, however, there are no consistent data about the influence of clinical parameters on parotid gland function. We studied a group of patients with head and neck malignancies before treatment with radiotherapy. We used Lashley cups to collect stimulated parotid saliva simultaneously from both parotid glands. Sizes of the parotid gland, gender, age, tobacco and alcohol consumption, and tumour characteristics were related to the function of the parotid gland. A considerable variability in parotid output was found with a range of 0.03-1.66 ml/min (mean 0.34 ml/min). None of the variables were correlated with parotid flow. These results are important, especially when evaluating effects of radiation on parotid gland function.


Involvement of position-147 for HLA-E expression.
HLA-E functions as an inhibitory signaling molecule of natural killer (NK) cell-mediated cytolysis. However, the cell surface expression of HLA-E molecules is quite restricted because of the limited repertoire of binding peptide sequences, such as signal peptides of other HLA molecules, especially on xenogeneic cells. In this study, we successfully determined that position-147 is an important amino acid position for cell surface expression by producing point substitutions. For further studies concerning transplantation therapy, the point substitution, Ser147Cys, that resulted in a single atom change, oxygen to sulfur, designated as HLA-Ev(147), led to a much higher expression on the human and pig cell surface and a greater inhibitory function against human NK cells than wild type HLA-E in an in vitro model system of pig to human xenotransplantation. Consequently, HLA-Ev(147) might be a promising alternative gene tool for future transplantation therapy such as xenotransplantation.


Morphometric and ultrastructural analyses of melanocytes, nevus cells, and melanoma cells.
Cytological atypia, revealed in the course of routine light microscopy, is considered a valuable indicator of malignancy in melanocytic lesions. A clear definition of the term cytological atypia, however, is lacking. Therefore, by morphometric analysis of ultrathin sections of 11 malignant melanomas (7 invasive, 3 in situ, and 1 lentigo maligna melanoma) and 10 compound nevi, we evaluated the discriminating power of the various facets of cytological atypia, i.e., nuclear area, area of the nucleolus, area of the total cell, and nuclear irregularity. In each case, at least 50 intraepidermal melanocytic cells were examined. The two-sided U-test showed significant differences between intraepidermal nevus and melanoma cells, with regard to the mean values (mean) and standard deviations (s) of the nuclear area (mean and s, p = 0.00011), area of the nucleolus (mean, p = 0.00043; s, p = 0.00011), and area of the total cell (mean, p = 0.00011; s, p = 0.00093). However, only the mean values and standard deviations of the nuclear area allowed a clear distinction in each individual case. The area of the nucleus can be estimated in the course of routine histology. We therefore think that the size and variation of the nuclear area should be considered in the histological differential diagnosis between malignant melanomas and benign nevi.


Decreased integrity of the monoaminergic tract is associated with a positive response to MPH in patients with vascular cognitive impairment - proof of principle study STREAM-VCI.
Patients with vascular cognitive impairment (VCI) are very heterogeneous in both symptoms and type of cerebrovascular pathology. This might be an important reason why there is no symptomatic treatment available for VCI patients. In this study, we investigated in patients with VCI, whether there was an association between a positive response to methylphenidate and galantamine and the type of cerebrovascular disease, structural damage to specific neurotransmitter systems, cerebral perfusion, and presence of co-morbid Alzheimer (AD) pathology. We included 27 VCI patients (mean age 67 years ± 8,30% female) from the STREAM-VCI trial who received placebo, methylphenidate(10 mg), and galantamine(16 mg) in a single challenge, cross-over design. In this study, we classified patients improving on a task for executive functioning after methylphenidate compared to placebo as methylphenidate responders (MPH+; resp. non-responders, MPH-) and patients improving on a task for memory after galantamine compared to placebo as galantamine responders (GAL+; resp. non-responders, GAL-). On baseline MRI, we visually assessed measures of cerebrovascular disease, automatically segmented white matter hyperintensities, used diffusion tensor imaging to visualize the integrity of monoaminergic and cholinergic neurotransmitter systems with mean diffusivity (MD) and fractional anisotropy (FA). Comorbid AD pathology was assessed using CSF or amyloid-PET. We tested differences between responders and non-responders using ANOVA, adjusting for age and sex. Nine patients were MPH+ vs 18 MPH-. MPH+ had higher MD (1.22 ± 0.07 vs 0.94 ± 0.05); p = .001) and lower FA (0.38 ± .01 vs 0.43 ± .01); p = .04) in the monoaminergic tract compared to MPH-. Eight patients were GAL+ and 18 GAL-. We found no differences between GAL+ and GAL- in any of the MRI measures. Information on co-morbid AD pathology was present in 17 patients. AD pathology tended to be more frequent in GAL+ vs GAL- (5(71%) vs 2(20%); p = .06). In patients with VCI, we found that decreased integrity of the monoaminergic tract is associated with a positive response to MPH. Responsiveness to galantamine may be related to co-morbid AD pathology.


Thyroid hormone kinetics: improved method for quantitative separation and measurement of the various radioiodothyronine injection.
An accurate and reproducible method for measurement of radioactive species in blood after in vivo injection of labelled iodothyronines is described. By extraction with high-affinity antisera, radioactive reverse T3 and T3 are separated from serum quantitatively. Radioiodide is quantitatively separated from radio-thyronine species and serum proteins by Sephadex G50 filtration. The residual mixture of radio-T4 and iodoprotein is quantitatively resolved by ion-exchange adsorption. Minimal misclassification of radiospecies occurs, and can be corrected for. Mean recoveries of various radiospecies added to serum were: radioiodide 98.9%, radio-rT3 87.6%, radio-L-T3 94.5%, radio-T4 98.0% and radioiodoprotein 94.5%. The performance of the method is superior to that of chemical methods such as trichloracetic acid precipitation, ion-exchange or alkaline Sephadex extraction, and chromatographic separation.


Evaluation of the diabetes self care scale: an illustration of the Rasch model of measurement.
This pilot study illustrates the use of a Rasch measurement model to evaluate the psychometric properties of the Diabetes Self Care Scale (DSCS). A convenience sample of 50 adults with diabetes at two local hospitals (one for profit and one public) in southern Louisiana responded to the survey questions. The instrument is comprised of 27 items and 6 rating categories. The Bigsteps Rasch measurement software was used for all analyses. Results indicated that respondent separation reliability was low (0.63), but item separation reliability was satisfactory (0.91). Internal validity was supported. Twenty-six items measure a single construct of diabetes self care. Construct validity was supported by the meaningfulness of the item difficulty order and by the consistency of that order across respondents. Rating scale analysis revealed that middle categories were not distinct steps in the progression of increasing diabetes self care. In addition to deleting an item producing inconsistent responses and combining adjacent categories (categories 1 and 2, and categories 3, 4, and 5), four recommendations for future research are provided.


Gender Differences in Outcomes of Patients With Mesothelioma.
Mesothelioma is a rare and deadly form of cancer, linked to asbestos exposure. Although the United Kingdom has banned asbestos, the incidence rate remains high. Previous research has indicated that female individuals have better survival than male individuals, but this has never been examined in the United Kingdom. Pleural mesothelioma cases from 2005 to 2014 were extracted from the United Kingdom Lung Cancer Dataset. Multivariable logistic regression was used to assess the clinical and demographic factors associated with gender. A multivariable Cox proportional hazards model and propensity matching methods were used to assess gender differences in overall survival while accounting for potential confounders. There were 8479 (87.8%) male and 1765 (17.2%) female individuals included in the analysis. Female individuals were significantly younger, with more epithelial histology than male individuals. Female individuals had significantly better overall survival (adjusted hazard ratio, 0.85, 95% confidence interval, 0.81-0.90). Results remained similar when stratifying by age and performance status, and when limiting to patients with epithelial histology. The study increases knowledge about gender differences in mesothelioma survival and is the first to directly examine this in the United Kingdom. It further disentangles the effects of age, histology, and health status. Increased estrogen may improve survival and could provide a potential target for future therapies.


Ovine Paratuberculosis Control in Australia Revisited.
OJD is no longer the serious animal health issue that it was for many Australian rural communities a decade and a half ago. Despite declining OJD prevalence as determined by abattoir surveillance, the disease continues to spread, with OJD extension programs required to continually address the misinformation promulgated by some disaffected producers as new areas have become affected. Improved regional and on-farm biosecurity, including the introduction of a risk-based trading system, may have contributed to improved attitudes to OJD control, although attitudinal differences between OJD endemic areas and where the disease is not well established remain. Declines in on-farm OJD prevalence are almost certainly attributable to the widespread uptake of vaccination programs, although encouraging the ongoing use of vaccination to prevent recrudescence and improved biosecurity when mortalities disappear, remains challenging. Vaccination has provided a robust strategy for managing OJD and contributed significantly to the health of Australian sheep and the lives of producers with affected properties. As vaccination offers a pathway to reduce the risk of MAP infection entering the human food chain from small ruminant products, it should be more widely adopted globally, accompanied by research efforts to improve efficacy and importantly, the safety of vaccination to both operators and livestock.


Dynamics of microbial community and changes of metabolites during production of type Ι sourdough steamed bread made by retarded sponge-dough method.
Dynamics of microbial community and changes of metabolites during production of type Ι sourdough steamed bread made by retarded sponge-dough method (SSB) were studied. Lactobacillus sanfranciscensis and Lactobacillus pontis were the dominant bacterial species. Particularly, relative abundances of Lactobacillus sanfranciscensis were significantly higher than that of other sub-dominant bacterial species. The dominant fungal species were Saccharomyces cerevisiae and Kazachstania humilis, and the latter was the most predominant. A stable bacterial and fungal consortia was established in sponge dough retarded from 12 to 24 h and main dough proofed from 30 to 60 min. Metabolism preference for maltose of Lactobacillus sanfranciscensis favoured a mutualistic association with maltose-negative Kazachstania humilis, and hence contributing to their competitiveness and dominance. Volatile compounds became more abundant with much more esters as sponge retarding time extended. Probably, the accumulation of organic acids and ethanol contributed mostly to formation of ethyl esters in sponge dough during retarding.


MoOx Nanoparticle Catalysts for d-Glucose Epimerization and Their Electrical Immobilization in a Continuous Flow Reactor.
Activity and immobilization of catalysts in liquid-phase reactions seem not to coexist. We report here the excellent activity of an MoOx nanoparticle (NP) catalyst for d-glucose epimerization to d-mannose and the electrical immobilization of NPs in a flow reaction. Prior to that, a green and one-pot method to synthesize the MoOx NPs (3.05 nm) via oxidizing metal Mo by hydrogen peroxide was presented. The NPs overwhelmed the reported catalysts including epimerase for d-glucose epimerization, originating from a strong interaction between the NPs and the reactant that was demonstrated by ex situ and in situ characterizations and theoretical calculations. The electrically charged feature of NPs inspired us to find a convenient way to "immobilize" them inside an activated carbon bed, and thereby, a flow reactor was assembled. The continuous epimerization was run under 24 V for 16 days with an almost unchanged activity, and only 3.2% of total Mo was lost.


Synthesis, spectroscopic characterization and in vitro anticancer activity of new platinum(II) complexes with some thione ligands in the presence of triethylphosphine.
Seven new platinum(II) complexes (1-7) of triethylphosphine (Et3P) and thiones (L) with general formula, cis-[Pt(Et3P)2(L)2]Cl2 were prepared and characterized by elemental analysis, FTIR and NMR (1H, 13C & 31P) measurements. The analytical and spectroscopic data suggested the formation of the desired complexes. The complexes were tested for in vitro cytotoxicity against four cell lines: Hela (human cervical adenocarcinoma), MCF-7 (human breast carcinoma), A549 (human lung carcinoma), and HTC15 (human colon carcinoma). The anticancer activity values of compounds 1-6 are much better than cisplatin and carboplatin as indicated by their IC50 values.


Selectivity of d[Cha4]AVP and SSR149415 at human vasopressin and oxytocin receptors: evidence that SSR149415 is a mixed vasopressin V1b/oxytocin receptor antagonist.
1 A possible role of arginine vasopressin (AVP) V(1b) receptor subtype in stress-related disorders has been recently highlighted by the discovery of the agonist [1-deamino-4-cyclohexylalanine] AVP (d[Cha(4)]AVP) and the antagonist SSR149415. Both compounds have been proposed to target specifically V(1b) receptors, since the reported affinities for the related V(1a), V(2) and oxytocin receptors are in the micromolar or submicromolar range. In the present study, we further investigated the binding affinities of d[Cha(4)]AVP and SSR149415 at recombinant human vasopressin V(1b) (hV(1b)) and oxytocin (hOT) receptors expressed in Chinese hamster ovary (CHO) cells and functional properties of both compounds at hV(1b), hV(1a), hV(2) and hOT receptors. 2 d[Cha(4)]AVP bound to hV(1b) receptors and hOT receptors with pK(i) values of 9.68+/-0.06 and 7.68+/-0.09, respectively. SSR149415 showed pK(i) values of 9.34+/-0.06 at hV(1b) and 8.82+/-0.16 at hOT receptors. 3 d[Cha(4)]AVP stimulated [Ca(2+)](i) increase in hV(1b)-CHO cells with a pEC(50) value of 10.05+/-0.15. It showed pEC(50) values of 6.53+/-0.17 and 5.92+/-0.02 at hV(1a) and hV(2) receptors, respectively, and behaved as a weak antagonist at hOT receptors (pK(B)=6.31+/-0.12). SSR149415 inhibited the agonist-induced [Ca(2+)](i) increase with pK(B) values of 9.19+/-0.07 in hV(1b)-CHO and 8.72+/-0.15 in hOT-CHO cells. A functional pK(i) value of 7.23+/-0.10 was found for SSR1494151 at hV(1a) receptors, whereas it did not inhibit 20 nM AVP response at hV(2) receptors up to 3 microM. 4 Data obtained confirmed the high potency and selectivity of d[Cha(4)]AVP at hV(1b) receptors, but revealed that SSR149415, in addition to the high potency at hV(1b) receptors, displays a significant antagonism at hOT receptors.


Generation of a human iPSC line ZZUNEUi014-A from a patient with antithrombin deficiency caused by mutation in SERPINC1 gene.
Inherited antithrombin (AT) deficiency is an autosomal dominant disorder associated with SERPINC1 mutations. In this study, we generated a human induced pluripotent stem cell (iPSC) line ZZUNEUi014-A from peripheral blood mononuclear cells of a female AT deficiency patient with the p. W27X (c. 80G > A) mutation in SERPINC1. This cell line expressed pluripotency markers, showed normal female karyotype and could differentiate into all three germ layers in vitro.


Population pharmacokinetics of treosulfan and development of a limited sampling strategy in children prior to hematopoietic stem cell transplantation.
There is an increasing interest in use of treosulfan (TREO), a structural analogue of busulfan, as an agent in conditioning regimens prior to hematopoietic stem cell transplantation (HSCT), both in pediatric and adult populations. The aim of this study was to develop a population pharmacokinetic model and to establish limited sampling strategies (LSSs) enabling accurate estimation of exposure to this drug. The study included 15 pediatric patients with malignant and non-malignant diseases, undergoing conditioning regimens prior to HSCT including TREO administered as a 1 h or 2 h infusion at daily doses of 10, 12, or 14 g/m2. A population pharmacokinetic model was developed by means of non-linear mixed-effect modeling approach in Monolix® software. Multivariate regression analysis and Bayesian method were used to develop 2- and 3-point strategies for estimation of exposure to TREO. Pharmacokinetics of TREO was best described with a two-compartmental linear model with proportional residual error. Following sampling schedules allowed accurate estimation of exposure to TREO: 1 h and 6 h or 1 h, 2 h, and 6 h for a TREO dose 12 g/m2 in a 1 h infusion, or at 2 h and 6 h or 2 h, 4 h, and 8 h for a TREO dose of 12 g/m2 and 14 g/m2 in a 2 h infusion. A two-compartmental population pharmacokinetic model of TREO was developed and successfully used to establish 2- and 3-point LSSs for accurate and precise estimation of TREO AUC0→∞.


Adrenergic and calcium-mediated subcellular redistribution of protein kinase C in primary neuronal cultures.
Incubation of primary neuronal cultures prepared from the brains of neonatal rats with 50 microM epinephrine resulted in the transient redistribution of protein kinase C from the cytosol to the particulate fraction. This effect occurred after 1 and 5 min of incubation and resulted in a decrease in cytosolic protein kinase C activity with a corresponding increase in particulate protein kinase C of approximately 30% and 15%, respectively. The epinephrine-stimulated translocation of protein kinase C was blocked by 1 microM prazosin indicating the involvement of alpha 1-adrenergic receptors. Further, inclusion of 0.1 microM Ca2+ in the homogenization buffer was found to significantly enhance the binding of protein kinase C to cellular membranes prepared from neuronal cultures. These results indicate that alpha 1-adrenergic receptors in neuronal brain cell cultures are linked to the activation of protein kinase C and that the mobilization of Ca2+ may enhance this effect.


Trends, Predictors, and Outcomes of Stroke After Surgical Aortic Valve Replacement in the United States.
Postoperative stroke is a devastating complication after aortic valve replacement (AVR). Our objective was to use a large national database to identify the incidence of and risk factors for stroke after AVR, as well as to determine incremental mortality, resource use, and cost of stroke. We identified 360,437 patients who underwent isolated surgical AVR between 1998 and 2011 from the National Inpatient Sample (NIH) database. Mean age was 66 ± 32 years. Multivariable regression and propensity matching were used to identify risk factors and the effect of stroke on outcomes. Patients were stratified according to the Elixhauser comorbidity score (ECS) into low- (0-5), medium- (6-15), and high-risk (16+) categories. Stroke after AVR occurred in 5,092 (1.45%) patients. The incidence of stroke declined from 1.69% in 1999 to 0.94% in 2011 (p < 0.001). Increasing age and higher comorbidities were the main predictors of stroke (each p < 0.001). The highest-volume centers (>200 AVRs/y) had the lowest rate of stroke (1.2%). After multivariable adjustment, high-volume centers had lower odds of stroke in medium-risk (odds ratio [OR], 0.59; 95% confidence interval [CI], 0.37-0.94) and high-risk patients (OR, 0.39; 95% CI, 0.22-0.68) compared with the lowest-volume centers. For low-risk patients, volume was not associated with stroke. Patients who experienced stroke were hospitalized for 4 days longer, had an average of $10,496 higher costs, and had 2.74 (95% CI, 1.97-3.80) times higher odds of in-hospital mortality compared with those who did not experience stroke (all p < 0.001). The incidence of stroke after AVR has decreased but remains a significant cause of morbidity in medium- and high-risk patients. Superior outcomes can be achieved in medium- to high-risk patients at high-volume centers.


Patellofemoral Pain.
Patellofemoral pain is characterized by insidious onset anterior knee pain that is exaggerated under conditions of increased patellofemoral joint stress. A variety of risk factors may contribute to the development of patellofemoral pain. It is critical that the history and physical examination elucidate those risk factors specific to an individual in order to prescribe an appropriate and customized treatment plan. This article aims to review the epidemiology, risk factors, diagnosis, and management of patellofemoral pain.


Clinical significance of aberrant microRNAs expression in predicting disease relapse/refractoriness to treatment in diffuse large B-cell lymphoma: A meta-analysis.
The clinical significance of aberrantly expressed microRNAs in predicting treatment response to chemotherapy in diffuse large B-cell lymphoma patients (DLBCL) remains uncertain. Feasibility of microRNA testing to predict treatment outcome was evaluated. Twenty-two types of aberrantly expressed microRNAs were associated with poor treatment response; pooled hazard ratio (HR) was 2.14 [95%CI:1.78-2.57, P < 0.00001]. DLBCL patients with aberrant expression of miR-155, miR-17/92 clusters, miR-21, miR-224, or miR-146b-5p had a higher risk of treatment resistance or shorter period of disease relapse/progression free survival, with HR = 2.71 (95%CI:1.66-4.42, P < 0.0001), HR = 2.70 (95%CI:1.50-4.85, P = 0.0010), HR = 2.20 (95%CI:1.31-3.69, P = 0.003), HR = 2.07 (95%CI:1.50-2.86, P < 0.00001), HR = 2.26 (95%CI:1.40-3.65, P = 0.0009), respectively. The association between aberrant expression of microRNAs and treatment response appears to be stronger in formalin-fixed-paraffin-embedded tissue (HR = 2.41, 95%CI:1.79-3.25, P < 0.00001) than in fresh-frozen samples (HR = 1.94, 95%CI: 1.22-3.08, P = 0.005) and peripheral blood samples (HR = 1.94, 95%CI:1.53-2.46, P < 0.00001). Mir-155, miR-17/92 clusters, miR-21, miR-224, and mir-146b-5p have value in predicting treatment response to chemotherapy in DLBCL.


The Plasticity of Our Fears: Affective Politics in the European Migration Crisis.
In the field of migration politics, a dominant rhetoric argues that liberal immigration and asylum policies must be avoided because they will inevitably lead to anti-immigration backlashes that exacerbate the very conditions they were supposed to remedy. Drawing on the work of German sociologist Heinrich Popitz and empirical data on the aftereffects of the European migration crisis, the article criticizes this "rhetoric of reaction" (Albert Hirschman) for ignoring the many variables shaping the consequences of more open borders. Backlashes to immigration are real and pose a constraint for liberal immigration policies, but these backlashes are not necessarily politically successful. Societies react neither uniformly nor automatically to rising immigration. A critical variable is the fear engendered by the (real, expected, or imagined) arrival of large numbers of migrants, and this fear can be either ramped up to paranoid levels or calmed by a politics of hope aimed at restoring what Popitz called the "human openness to the world."


Metallothionein-3: 63 Cu(I) binds to human 68 Zn7 -βα MT3 with no preference for Cu4 -β cluster formation.
Human metallothioneins (MTs) are involved in binding the essential elements, Cu(I) and Zn(II), and the toxic element, Cd(II), in metal-thiolate clusters using 20 reduced cysteines. The brain-specific MT3 binds a mixture of Cu(I) and Zn(II) in vivo. Its metallation properties are critically important because of potential connections between Cu, Zn and neurodegenerative diseases. We report that the use of isotopically pure 63 Cu(I) and 68 Zn(II) greatly enhances the element resolution in the ESI-mass spectral data revealing species with differing Cu:Zn ratios but the same total number of metals. Room temperature phosphorescence and circular dichroism spectral data measured in parallel with ESI-mass spectral data identified the presence of specific Cu(I)-thiolate clusters in the presence of Zn(II). A series of Cu(I)-thiolate clusters form following Cu(I) addition to apo MT3: the two main clusters that form are a Cu6 cluster in the β domain followed by a Cu4 cluster in the α domain. 63 Cu(I) addition to 68 Zn7 -MT3 results in multiple species, including clustered Cu5 Zn5 -MT3 and Cu9 Zn3 -MT3. We assign the domain location of the metals for Cu5 Zn5 -MT3 as a Cu5 Zn1 -β cluster and a Zn4 -α cluster and for Cu9 Zn3 -MT3 as a Cu6 -β cluster and a Cu3 Zn3 -α cluster. While many reports of the average MT3 metal content exist, determining the exact Cu,Zn stoichiometry has proven very difficult even with native ESI-MS. The work in this paper solves the ambiguity introduced by the overlap of the naturally abundant Cu(I) and Zn(II) isotopes. Contrary to other reports, there is no indication of a major fraction of Cu4 -β-Znn -α-MT3 forming.


Familial abdominal aortic aneurysm: prevalence and implications for screening.
The high prevalence of abdominal aortic aneurysm (AAA) in men over the age of 65 has led to the establishment of ultrasound screening programmes for this group. The apparent familial tendency towards AAA formation suggests that relatives of aneurysm patients may form another subpopulation in whom screening is appropriate. The first degree relatives of 100 consecutive aneurysm patients were identified. Of 110 relatives over 50 years of age, two were known to have had AAA and ultrasound scans were performed on 74, providing information on aortic size for 76 relatives (69%). No further aortic aneurysms (antero-posterior diameter > or = 4.0 cm) were found on scanning. However, nine relatives were demonstrated to have aortic dilatation (2.5-3.9 cm). Aortic dilatation was observed in 21% of male first degree relatives over 50 years of age, affecting 27% of sons and 17% of brothers. Only 4% of the sisters and none of the daughters were found to have aortic dilatation. The prevalence of aortic enlargement seems to be sufficiently high amongst male first degree relatives of AAA patients over 50 years of age to justify aortic screening.


Miracles of Herbal Phytomedicines in Treatment of Skin Disorders: Natural Healthcare Perspective.
Human skin is considered as the first line of defense and barrier against the majority of infections caused through the skin that affect humans. Healthy skin promotes a healthy body that can be achieved with the usage of modern, allopathic and natural remedies. Major skin ailments affecting humans are skin cancers, eczema, herpes infection, fungal infection, anti-aging, itching, insect bites, pemphigus vulgaris, trauma, psoriasis, athlete's foot infections, rashes, skin pigmentation, acne, major and minor wound infections that are slowly becoming a burden on health care. Skin infections can be treated from sources that originate from animals and plants. In spite of advancements in science and technology, the emergence of natural herbal remedies for managing skin disorders has become a pivotal and essential contributor in treating skin infections due to increased demand for herbals and their lower price, and continuous adverse effects of modern medicines. In the recent era, herbal extracts and their phytomedicines have made a vital contribution to human health care. Herbal products nowadays are considered as a single line of treatment for many diseases like Cancers, Diabetes, Cardiovascular and Brain disorders, thereby creating awareness regarding purity, efficacy and safety of herbal medicines for health care management. Many therapeutically active natural herbal resources like Aloe, Neem, Liquorice, Tulsi, Amla, Papaya, Ginger and Eucalyptus are potent and safe in the treatment of dermatological infections. This review article summarizes the significance of herbal plants for protecting, treating and minimizing skin infections through the utility of herbal pharmaceuticals like creams, decocted extracts, poultice, paste and lotions that aid in the treatment of skin infections and diseases at a relatively lower cost with lesser side effects as compared to modern and allopathic medicines.


Distinct patterns of MCM protein binding in nuclei of S phase and rereplicating SV40-infected monkey kidney cells.
Simian Virus 40 (SV40) infection of growth-arrested monkey kidney cells stimulates S phase entry and the continued synthesis of both viral and cellular DNA. Infected cells can attain total DNA contents as high as DNA Index, DI = 5.0-6.0 (10-12C), with host cell DNA representing 70-80% of the total. In this study, SV40-infected and uninfected control cells were compared to determine whether continued DNA replication beyond DI = 2.0 was associated with rebinding of the minichromosome maintenance (MCM) hexamer, the putative replicative helicase, to chromatin. Laser scanning cytometry was used to measure the total expression per cell and the chromatin/matrix-association of two MCM subunits in relation to DNA content. MCM2 and MCM3 proteins that were associated with the chromatin/matrix fraction in G1 phase of both uninfected and SV40-infected cells were gradually released during progression through S phase. However, in SV40-infected cells that progressed beyond DI = 2.0, chromatin/matrix-associated MCM2 and MCM3 remained at the low levels observed at the end of S phase. Rereplication was not preceded by an obvious rebinding of MCM proteins to chromatin, as was observed in G1 phase. The rereplication of host cell DNA in the absence of the reassociation of MCM proteins with chromatin indicates that SV40 infection induces a novel mechanism of licensing cellular DNA replication.


Predictors of Futile Recanalization After Endovascular Treatment in Patients with Acute Ischemic Stroke in a Multicenter Registry Study.
Futile recanalization, defined as the early recanalization of an occluded artery failing to improve neurological outcome, remains a persistent concern in the endovascular treatment of acute ischemic stroke. We investigated the occurrence and predictors of futile recanalization after endovascular treatment in a nationwide multicenter stroke registry study. The subjects consisted of eligible patients from the Acute Ischemic Stroke Cooperation Group of Endovascular Treatment registry study (2015-2017). Subjects with acute anterior large vessel occlusion who achieved successful angiographic recanalization (defined as modified Thrombolysis in Cerebral Infarction grades 2b or 3) by endovascular treatment were dichotomized into the futile-recanalization group (with a modified Rankin Scale score of 3-6) and the favorable-recanalization group (with a modified Rankin Scale score of 0-2) according to 90-day functional independence. Logistic regression analysis was performed to investigate predictors of futile recanalization. Futile recanalization was observed in 200 (49.6%) out of 403 patients. On multivariate analysis, older age (>74 vs. ≤74; odds ratio (OR), 2.41; 95% confidence interval (CI), 1.31-4.44; P=0.005), high baseline National Institutes of Health Stroke Scale score (>21 vs. ≤13; OR, 2.52; 95% CI, 1.21-5.28; P=0.014), delayed puncture to recanalization time (>80 vs. ≤80 min; OR, 2.75; 95% CI, 1.67-4.51; P=0.000), and the use of general anesthesia (OR, 1.90; 95% CI, 1.15-3.14; P=0.012) were positively associated with futile recanalization after mechanical thrombectomy. The incidence of futile recanalization is common following endovascular treatment among Asian patients with anterior circulation occlusion. Advanced age, higher baseline National Institutes of Health Stroke Scale score, delayed puncture to reperfusion, and the use of general anesthesia are associated with lower functional independence 90 days post-treatment despite successful recanalization.


Environmental risks and problems of the optimal management of an oil shale semi-coke and ash landfill in Kohtla-Järve, Estonia.
The main wastes of the Estonian shale oil industry - oil shale semi-coke and ashes - are deposited in landfills. The Kohtla-Järve oil shale semi-coke and ash landfill, which is likely the largest of its kind in the World, was started in 1938. The environmental risks connected with the landfill were assessed and prioritized. The most significant hazard to human health is emission of harmful landfill gases and the water contamination in the local river network is harmful for aqueous organisms. The spatial expansion of subsurface contamination predicted by the groundwater transport model completed is practically insignificant from the viewpoint of health services. The landfill's leachates must be captured and purified, and the closed part of the landfill should be covered by greenery. The partial landfill capping recently executed is useless. The EU Landfill Directive requirements imposed on the hydraulic resistance of geological barriers cannot prevent the leakage of contaminants from a landfill.


Response of maize (Zea mays L. saccharata Sturt) to different concentration treatments of deltamethrin.
The aim of this study was to investigate the effect of the deltamethrin pesticide on the biological properties of maize (Zea mays L. saccharata Sturt). Maize seeds were exposed to environmentally relevant dosages (0.01, 0.05, 0.1 and 0.5 ppm) of deltamethrin. On the 7th day of germination, morphological, anatomical and physiological responses were determined. All seedling growth characters were decreased with increasing deltamethrin levels. The most negative effect on the radicle length of maize was observed by the highest deltamethrin concentration with a 61% decrease (P <0.05). Both stomatal density and stomatal dimension reduction were caused by increasing concentrations of deltamethrin. Moreover, the pigments like chlorophyll a, chlorophyll b, total chlorophyll and caretonoids decreased with the increase in deltamethrin concentration. Conversely, anthocyanin and proline content increased in parallel with deltamethrin concentration. As a result, all morphological traits and pigments except for proline and anthocyanin were significantly reduced with an increase in pesticide concentration, compared to control (P <0.05).


Mutations of signal-transducing G proteins in human disease.
Heterotrimeric guanine nucleotide binding proteins (G proteins) couple a large number of cell surface receptors to their intracellular effector molecules, such as enzymes or ion channels. Mutations of G proteins can lead to either activation or inactivation of the corresponding signal transduction pathway and thus cause clinical symptoms. Mutations of heterotrimeric G proteins have been found in a number of endocrine tumors, the McCune-Albright syndrome, Albright's hereditary osteodystrophy, and a combination of precocious puberty and pseudohypoparathyroidism Ia. The identification of the molecular defects underlying the above disorders and the investigation of their functional consequences for metabolism and growth regulation have been the subject of many studies over the past few years. A close understanding of these pathophysiologic mechanisms is crucial for the development of therapeutic strategies.


Uptake, exchange, and release of GABA by cerebellar glomeruli.
Glomerular particles were isolated from the bovine cerebellar vermis and studied in vitro to further assess the possibility that gamma-aminobutyric acid (GABA) is utilized as a neurotransmitter in this synaptic complex. Cerebellar glomeruli accumulated [3H]GABA at two different high affinity sites, with affinities (KT) of 2.2 X 10(-6) M and 3.0 X 10(-5) M. These uptake sites could not be distinguished on the basis of their temperature sensitivities, sodium dependence, substrate specificities or responses to metabolic inhibitors. Although an exchange process contributed to the uptake measured in these experiments, a considerable amount of the [3H]GABA accumulated by glomerular particles was stored in an osmotically-sensitive, nonexchangeable pool. Glomerular particles preloaded with [3H]GABA exhibited a Ca2+-independent release of this amino acid in response to membrane depolarization. However, when preloaded glomerular particles were exposed to unlabeled GABA, which presumably displaced [3H]GABA from the exchangeable pool, a K+-evoked and Ca2+-dependent release of the remaining [3H]GABA occurred. The observed net uptake, together with the depolarization-induced and Ca2+-dependent release, of [3H]GABA from glomerular particles supports the suggestion that functionally active GABAergic synapses are present in these structures.


Improved separation and analysis of plasma amino acids by modification of the MassTrak™ AAA Solution Ultraperformance® liquid chromatography method.
Ultraperformance® Liquid Chromatography (UPLC) is increasingly used for quantitative amino acid screening. The Waters MassTrak™ UPLC Amino Acid Analysis (AAA) Solution kit offers rapid analysis with minimal sample preparation. We describe a simple modification of this method enabling enhanced chromatographic separation of previously problematic analytes with improvements in quantification. The commercial UPLC method was compared with our modified version of the same method. The modification incorporates eluent buffer of increased organic content run at reduced column temperature. UPLC methods were compared by analyzing amino acids from 57 plasma samples. A comparison (n=131) between the modified UPLC method and ion-exchange chromatography was also carried out. The commercial method produced a large negative bias for Tyrosine (-22.72%±14.10) and ornithine (-15.02%±10.07). Assay imprecision of Tyrosine using the commercial method (mean Tyrosine: 72.58 and 31.17μmol/l) produced values of 10.86% and 21.12% respectively, compared with the modified method (3.39% and 4.47%). The comparison of modified UPLC and ion-exchange methods was favorable, validating the improvements observed in amino acid quantification. The modified UPLC method has eliminated significant bias associated with the commercially available method. The modification is simple, robust and readily adaptable to the current MassTrak™ AAA Solution kit for clinical applications.